S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300001 Introduction Monge-Nájera Julián ,Costa Rican Distance University 09 2004 2004 52 XIII XVII
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300002 Hace 500 años,hace 50 años …Tiempo de descubrimientos y fundaciones Morera Bernal , 09 2004 2004 52 XIX XXX
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300003 Interethnic variability and admixture in Latin America - social implications Salzano Francisco M ,Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil 09 2004 2004 52 405 415

Past and present attempts to classify and characterize the human biological variability are examined, considering the race concept, ethnic identification problems, assortative mating based on ethnicity, and historical genetics. In relation to the latter, a review is made of the methods presently available for admixture quantification and of previous studies aimed at the characterization of the parental continental contributions to Latin American populations, with emphasis in global evaluations of the Costa Rican and Brazilian gene pools. Finally, the question of racism and discrimination is considered, including the relation between human rights and affirmative actions. The right to equal opportunity should be strictly respected. Biological inequality has nothing to do with the ethical principle that someone’s position in a given society should be an accurate reflection of her/his individual ability. Rev. Biol. Trop. 52(3): 405-415. Epub 2004 Dic 15

Son examinados los intentos pasados y presentes de clasificar y caracterizar a la variabilidad biológica humana, considerando el concepto de raza, los problemas de identificación étnica, el matrimonio selectivo basado en la etnicidad, y la historia genética. En relación con la última, se hace una revisión de los métodos disponibles actualmente para la cuantificación de la mezcla y de los estudios previos enfocados en la caracterización de la contribuciones parentales de origen continental a las poblaciones Latinoamericanas, con énfasis en las evaluaciones globales de los acervos genéticos de de Brasil y Costa Rica. Finalmente, se considera el tema del racismo y la discriminación, incluyendo la relación entre los derechos humanos y las acciones afirmativas. El derecho a iguales oportunidades debe ser estrictamente respetado. La inequidad biológica no tiene nada que ver con el principio ético de que la posición de cualquiera en una sociedad dada debe ser un reflejo exacto de sus habilidades individuales.

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Anthropol 1970 11 Ribeiro D As Américas e a Civilização As Américas e a Civilização 1977 Petrópolis Vozes Ribeiro-dos-Santos A.K.C Pereira J.A Lobato M.F.R Carvalho B.M Guerreiro J.F Santos S.E.B Dissimilarities in the process of formation of Curiaú, a semi-isolated Afro-Brazilian population of the Amazon region Am. J. Hum. Biol 2002 14 Roberts D.F Hiorns R.W The dynamics of racial admixture Am. J. Hum. Genet 1962 14 Roberts D.F Hiorns R.W Methods of analysis of the genetic composition of a hybrid population Hum. Biol 1965 37 Rodas C Gelvez N Keyeux G Mitochondrial DNA studies show asymmetrical Amerindian admixture in Afro-Colombian and Mestizo populations Hum. Biol 2003 75 Rosenberg N.A Pritchard J.K Weber J.L Cann H.M Kidd K.K Zhivotovsky L.A Feldman M.W Genetic structure of human populations Science 2002 298 Salzano F.M Human races: myth, invention, or reality? 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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300004 Scientific publications about DNA structure-function and PCR technique in Costa Rica: A historic view (1953-2003) Albertazzi Federico J ,Universidad de Costa Rica San Pedro de Montes de Oca San José Costa Rica 09 2004 2004 52 417 421

The spreading of knowledge depends on the access to the information and its immediate use. Models are useful to explain specific phenomena. The scientific community accepts some models in Biology after a period of time, once it has evidence to support it. The model of the structure and function of the DNA proposed by Watson & Crick (1953) was not the exception, since a few years later the DNA model was finally accepted. In Costa Rica, DNA function was first mentioned in 1970, in the magazine Biología Tropical (Tropical Biology Magazine), more than 15 years after its first publication in a scientific journal. An opposite situation occurs with technical innovations. If the efficiency of a new scientific technique is proved in a compelling way, then the acceptance by the community comes swiftly. This was the case of the polymerase chain reaction, or PCR. The first PCR machine in Costa Rica arrived in 1991, only three years after its publication. Rev. Biol. Trop. 52(3): 417-421. Epub 2004 Dic 15.

La diseminación del conocimiento depende de la disponibilidad de la información y aplicar dicha información para resolver una problema. Los modelos sirvan para explicar fenómenos determinados. En Biología los modelos son aceptados por la comunidad científica después de cierto tiempo si ha probado su validez y reconocido la evidencia para apoyar dicho modelo. El modelo estructural y función de la molécula de ADN propuesto por Watson y Crick (1953) no fue la excepción pues tardó varios años en ser completamente aceptado por la comunidad científica. En Costa Rica la primera publicación relacionada con la función del ADN fue en la Revista Biología Tropical fue en 1970, más de 15 años después de ser propuesta. La situación contraria se presenta cuando son innovaciones técnicas. Si la eficiencia es demostrada, rápidamente se incorpora dentro de la comunidad. Este fue el caso de la reacción en cadena de la polimerasa, abreviado en inglés como "PCR". La primera máquina de "PCR" llegó a Costa Rica en 1991, tan solo tres años después de la publicación de la técnica.

 Publications genetics DNA PCR Costa Rica Publicaciones genética ADN PCR Costa Rica Aguilar T 50 years of the Revista de Biologia Tropical: its contribution to the development of the Geo-Paleontology Rev. Biol. Trop 2002 50 Alegría R Análsis de la organización genómica de la salamandra Bolitoglossa subpalmata Análsis de la organización genómica de la salamandra Bolitoglossa subpalmata 1988 Arrieta G Hernández A Espinoza A.M Diversity of Bacillus thuringiensis strains isolated from coffee plantations infested with the coffee berry borer Hypothenemus hampei Rev. Biol. Trop 2004 52 Bickers J.N Elizondo J Zomer M Hemoglobinopatías Acta Méd. Costarric 1965 8 Bustamante W Alpizar A Hernandez S Pacheco A Vargas N Herrera M.L Vargas A Caballero M Garcia F Predominance of vanA genotype among vancomycin-resistant Enterococcus isolates from poultry and swine in Costa Rica Appl. Environ. Microbiol 2003 69 Castro Volio I Pasado, presente y futuro de la citogenética humana en Costa Rica Rev. Biol. Trop 2004 a 52 Castro Volio I El diagnóstico prenatal de defectos cromosómicos en Costa Rica Rev. Biol. Trop 2004 b 52 Castro Volio I Montero Umaña C Jiménez Cruz G Características cromosómicas asociadass con leucemias y otras hemopatías en Costa Rica Rev. Biol. Trop 1993 41 Céspedes M Gutiérrez M.V Holbrook N.M Rocha O.J Restoration of genetic diversity in the dry forest tree Swietenia macrophylla (Meliaceae) after pasture abandonment in Costa Rica Mol. Ecol 2003 12 Cortés J Nielsen V Marine science in Revista de Biologia Tropical in its 50th anniversary Rev. Biol. Trop 2002 50 Dorsch M Moreno E Stackebrandt E Nucleotide sequence of the 16S rRNA from Brucella abortus Nucleic Acids Res 1989 17 Espinoza A.M León P.E Macaya G Fuentes A.L Gutiérrez J.M Estructura y función de los cromosomas plumulados Rev. Biol. Trop 1980 28 Fresco J.R Simons R.W Grunberg-Manago M From DNA melting profiles to tRNA crystals and RNA chaperones: How the secondary and tertiary structures of ribonucleic acids were discovered- A personal recollection RNA Structure and Function RNA Structure and Function 1998 ^eNew York Cold Spring Harbor Lab Gutiérrez J.M Biomedical research in Revista de Biologia Tropical Rev. Biol. Trop 2002 50 Gutiérrez J.M Bolaños R Cariotipos de las principales serpientes coral (Elapidae: Micrurus) de Costa Rica Rev. Biol. Trop 1979 27 Gutiérrez J.M Bolaños R Poliformismo cromosómico intraespecífico en la serpiente coral Micrurus nigrocinctus (Ophidia: Elapidae) Rev. Biol. Trop 1981 29 Gutiérrez J. M Solorzano A Cerdas L Estudio cariológico de cinco especies de serpientes costarricense de la familia Colubridae Rev. Biol. Trop 1984 32 Gutiérrez J.M Taylor R.T Bolaños R Cariotipos de diez especies de serpientes costarricenses de la familia Viperidae Rev. Biol. Trop 1979 27 Hanson P Fifty years of entomological publications in the Revista de Biologia Tropical Rev. Biol. Trop 2002 50 Lamar W.W Sasa M A new species of hognose pitviper, genus Porthidium, from the southwestern Pacific of Costa Rica (Serpentes: Viperidae) Rev. Biol. Trop 2003 51 Leal A Morera B Del Valle G Heuss D Kayser C Berghoff M Villegas R Hernández E Méndez M Hennies H.C Neundorfer B Barrantes R Reis A Rautenstrauss B A second locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 19q13.3 Am. J. Hum. Genet 2001 68 León J Half century of botany publishing in Revista de Biologia Tropical Rev. Biol. Trop 2002 50 León P.E Biotechnology for developing countries: The case of the Central American isthmus Ann. N.Y. Acad. Sci 1993 700 León P.E Chromosome numbers of some Costa Rican anurans Rev. Biol. Trop 1969 17 Lizano S Angulo Y Lomonte B Fox J.W Lambeau G Lazdunski M Gutiérrez J.M Two phospholipase A2 inhibitors from the plasma of Cerrophidion (Bothrops) godmani which selectively inhibit two different group-II phospholipase A2 myotoxins from its own venom: isolation, molecular cloning and biological properties Biochem. J 2000 346 Lynch E.D Lee M.K Morrow J.E Welcsh P.L León P.E King M.C Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous Science 1997 278 Macaya G Thiery J.P Bernardi G An approach to the organization of eukaryotic genomes at a macromolecular level J. Mol. Biol 1976 108 Monge-Nájera J Díaz L Thirty-five years of Tropical biology: a quantitative history Rev. Biol. Trop 1988 36 Mora M Herrera A Léon P.E The genome of Epiperipatus biolleyi (Peripatidae), a Costa Rican onychophoran Rev. Biol. Trop 1996 44 Morales-Cordero A.I Morera B Jiménez-Arce G Sánchez-Rivera G Calafell F Barrantes R Allele frequencies of the markers LDLR, GYPA, HBGG, D7S8, Gc, HLA-DQA1, and D7S80 in the general and minority populations of Costa Rica Forensic Sci. Int 2001 124 Morera-Brenes B Sierra R Barrantes R Helicobacter pylori in a Costa Rican Dyspeptic Patient Population Eur. J. Clin. Microbiol. Infect. Dis 1994 13 Morera B Sánchez-Rivera G Jiménez-Arce G Calafell F Morales-Cordero AI Nicaraguan population data on LDLR, GYPA, HBGG, D7S8, Gc, and HLA-DQA1 loci Rev. Biol. Trop 2001 49 Muñoz M Bolaños I Arrieta G Espinoza A.M Expression of the rice hoja blanca virus (RHBV) non-structural protein 3 (NS3) in Escherichia coli and in situ localization in RHBV-infected tissues Rev. Biol. Trop 2004 52 Rodríguez L. L Letchworth G.J Spiropoulou C.F Nichol S.T Rapid detection of vesicular stomatitis New Jersey virus in clinical samples by using the polymerase chain reaction J. Clin. 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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300005 Importancia de la genealogía aplicada a estudios genéticos en Costa Rica Meléndez Obando Mauricio O ,Asociación Costarricense de Genealogía e Historia (ASOGEHI) y Academia Costarricense de Ciencias Genealógicas (ACCG) Paseo de los Estudiantes San José Costa Rica 09 2004 2004 52 423 450

The importance of genealogy applied to genetic research in Costa Rica. The extensive development of genealogical studies based on archival documents has provided powerful support for genetic research in Costa Rica over the past quarter century. As a result, several questions of population history have been answered, such as those involving hereditary illnesses, suggesting additional avenues and questions as well. Similarly, the preservation of massive amounts of historical documentation highlights the major advantages that the Costa Rican population offers to genetic research. Rev. Biol. Trop. 52(3): 423-450. Epub 2004 Dic 15.

El amplio desarrollo de los estudios genealógicos basados en la documentación custodiada en los archivos históricos ha representado un fuerte apoyo a la investigación genética en Costa Rica durante el último cuarto de siglo y como resultado de tal interacción se han podido responder algunas interrogantes sobre la historia poblacional, sobre varias enfermedades hereditarias y ha dejado vislumbrar la de otras; asimismo, deja entrever enormes ventajas pontenciales de la población costarricense como modelo para los estudios genéticos.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300006 Evolution and Innovations of the National Neonatal and High Risk Screening Program in Costa Rica de Céspedes Carlos Saborío Manuel Trejos Rafael Abarca Gabriela Sánchez Avelino ,National Children Hospital San José Costa Rica 09 2004 2004 52 451 466

We present the evolution, organization and results of the National Neonatal and High Risk Screening Program in Costa Rica (PNT). This program has been working uninterruptedly for more than fourteen years. Costa Rica currently has a literacy rate of 95%. To August 2004 the rate of infant mortality was 9.74 per 1000 births and to 2003, life expectancy was 76.3 years for men and 81.1 years for women. The control of infectious and parasitic diseases, as well as of severe malnutrition, has given room to a prevalence of chronic diseases with a pathology profile similar to that of a developed country. The clinical observation, mainly starting from early 70s, of a growing number of patients with mental retardation and other disabilities caused by congenital hypothyroidism and hereditary metabolic diseases that could have been prevented in many cases with an early diagnosis and opportune treatment, led us to the decision to implement a systematically massive neonatal screening for these diseases. The presence of a single Public System of Social Security in Costa Rica, which currently includes from primary health care up to the hospitals of tertiary attention, with a single Children’s Hospital for the whole country, as well as communication facilities, are factors that offered, in principle, favorable conditions for this effort, even for a developing country. To September 2004, 835,217 children have been screened. There is a coverage of 95.1% of the newborns in the country. Also to this date, 259 children with congenital hypothyroidism, 18 with phenylketonuria, 20 with the maple syrup disease, 30 with congenital adrenal hyperplasia and 10 with galactosemia have been detected, confirmed and treated, for a total of 337 children that were spared of mental retardation, other disabilities and even death. Massive neonatal screening for organic acidemias recently started in June of 2004. Cystic fibrosis is under a pilot study and the screening for hemoglobinopathies and toxoplasmosis is planned. The Center for Prevention of Disabilities, which started its functions on September 23, 2002, made feasible to integrate neonatal screening, high risk screening and diagnostic confirmation of the diseases now included in the national screening program as well as those to be added in the future. Rev. Biol. Trop. 52(3): 451-466. Epub 2004 Dic 15.

Presentamos la evolución, organización y los resultados del Programa Nacional de Tamizaje Neonatal y de Alto Riesgo en Costa Rica (PNT). Este programa ha estado trabajando ininterrumpidamente por más de catorce años. Actualmente Costa Rica tiene una tasa de alfabetización del 95%. En agosto de 2004 la tasa de mortalidad infantil fue de 9.74 por 1000 nacimientos y en el 2003, la expectativa de vida era de 76.3 años para hombres y de 81.1 para mujeres. El control de las enfermedades infecciosas y parasíticas, así como de la malnutrición severa, ha dado lugar a la prevalencia de enfermedades crónicas con un perfil patológico similar a los de los países desarrollados. La observación clínica, principalmente iniciando desde los años 70, de un número creciente de pacientes con retardo mental y otras discapacidades causadas por hipotiroidismo congénito y enfermedades metabólicas hereditarias que podrían haber sido prevenidas en muchos casos con un diagnóstico temprano y un tratamiento oportuno, nos llevo a tomar la decisión de implementar un sistema de tamizaje neonatal masivo para estas enfermedades. La presencia de un sistema público de seguridad social en Costa Rica, el cual actualmente incluye desde la atención primaria de la salud hasta la atención terciaria en los hospitales, con unúnico Hospital de Niños para todo el país, así como las facilidades de comunicación, son factores que ofrecen, en principio, condiciones favorables para este esfuerzo, aun en un país subdesarrollado. De esta manera, luego de un Decreto Ejectutivo, el PNT empezó en marzo de 1990. Las enfermedades incluidas desde el principio consistían del hipotiroidismo congénito, fenilcetonuria, y jarabe de arce. La hiperplasia adrenal congénita y la galactosemia fueron incluidas en enero de 2002 después de un programa piloto (1999-2000). Para setiembre de 2004 han sido tamizados 835217 niños. Hay una cobertura del 95.1% de los nacimientos del país. También para esta fecha, han sido detectados, confirmados y tratados 259 niños con hipotiroidismo congénito, 18 con fenilcetonuria, 20 con jarabe de arce, 30 con hiperplasia adrenal congénita y 10 con galactosemia; para un total de 337 niños que fueron salvados del retardo mental, otras discapacidades o incluso de la muerte. Además de las enfermedades antes mencionadas, y después de un proceso inicial de tamizaje del alto riesgo, y diagnóstico de acidemias orgánicas por espectrometría de masas en tandem (MS/MS), el tamizaje masivo neonatal de este tipo de enfermedades empezó recientemente en junio de 2004. Se han encontrado 3 casos de acidemia propiónica y 2 casos de Deficiencia de Acil-CoA deshidrogenasa de cadena media (MCAO). Un estudio piloto ha empezado para el tamizaje de la fibrosis quística; y esperamos que las hemoglobinopatías y la toxoplasmosis de sumen a la lista en un futuro próximo. El Centro de Prevención de Discapacidades del Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", fue diseñado y construido en función de las necesidades de optimización y amplificación del tamizaje en Costa Rica. En este Centro fue posible integrar convenientemente el tamizaje neonatal, el tamizaje de alto riesgo, y la confirmación del diagnóstico de las enfermedades ahora incluidas en el programa nacional, así como de las que se adicionen en el futuro. La combinación física y organizacional con los correspondientes servicios clínicos especializados del Hospital también facilita el cumplimiento de los objetivos fundamentales del tamizaje, principalmente la detección y tratamiento oportunos de los niños afectados. El Centro de Prevención de Discapacidades, que empezó a funcionar en setiembre de 2002, también representa una puerta que abre el sistema de salud costarricense a la práctica de la medicina del siglo 21 y a la genómica aplicada

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300007 Genética de la esquizofrenia: avances en el estudio de genes candidatos Pacheco Adriana Raventós Henriette ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 467 473

Genetics of Schizophrenia: advances in the study of candidate genes. Schizophrenia is one of the most severe mental disorders that affect 1% of the population worldwide. It is clear that both genetic and environmental factors participate in its etiology. Nonetheless, the effort to identify susceptibility genes has been difficult and there are no unequivocal findings until now. Notwithstanding this, during the last couple of years, a group of candidate genes has been identified because of their possible role in the physiopathology or by association and linkage studies. In this article, the role of these genes is summarized as well as the results of the studies conducted in Costa Rica by our group. Rev. Biol. Trop. 52(3): 467-473. Epub 2004 Dic 15.

La esquizofrenia es una de las enfermedades mentales severas que afecta a un 1% de la población mundial. Es claro que en su etiología participan factores genéticos y ambientales. Sin embargo, la identificación de genes de susceptibilidad ha sido difícil y no hay resultados inequívocos. A pesar de esto, en los últimos años se han identificado un grupo de genes candidatos por su posible fisiopatología o por estudios de asociación y ligamiento. En este artículo se revisa el papel de estos genes y los resultados de los estudios realizados en Costa Rica por nuestro grupo.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300008 Genetics of hereditary motor and sensory neuropathy and the Costa Rican contribution Leal Alejandro ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 475 483

Hereditary motor and sensory neuropathy (HMSN) or Charcot-Marie-Tooth disease (CMT) is the most common hereditary illness of the peripheral nervous system. The genetics and the physiopathological aspects of the disease clarified until know, are here summarized. More than twenty genes and ten additional loci have been related with HMSN. These findings contribute to understand the metabolism of peripheral nerves and give the basis for molecular diagnostics and future therapy. Several Costa Rican families with CMT have been identified, specially with axonal forms. Two families present mutations in the myelin protein zero gene (MPZ). In addition, linkage have been found between the disease and locus 19q13.3 in an extended family, and a mutation segregating with the disease is present in a candidate gene of the critical interval. Costa Rica has several advantages for genetical studies, that can contribute importantly in the generation of knowledge in the neurogenetical field. Rev. Biol. Trop. 52(3): 475-483. Epub 2004 Dic 15.

El grupo de neuropatías motoras y sensoriales hereditarias (HMSN) o enfermedad de Charcot-Marie-Tooth (CMT) es el padecimiento hereditario más común del sistema nervioso periférico. El propósito de este trabajo es resumir los aspectos genéticos y fisiopatológicos más actuales de esta enfermedad. Más de veinte genes y diez loci adicionales han sido relacionados con HMSN. Estos hallazgos han contribuido con la comprensión del metabolismo de los nervios periféricos y sirven de base para el diagnóstico molecular y el diseño de terapias. Diversas familias costarricenses con CMT han sido identificadas: dos de ellas presentan mutaciones en el gen que codifica por la mielina proteína cero (MPZ). Además, un análisis de ligamiento localizó el gen que causa una forma axonal de la enfermedad en el cromosoma 19q13.3 en una extensa familia; también se detectó en esa región una mutación que co-segrega con la enfermedad y que modifica la secuencia de un gen candidato. Costa Rica presenta numerosas ventajas para estudios genéticos, que pueden contribuir en la generación de conocimiento en el área de la neurogenética.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300009 The dystrophinopathies in Costa Rica Azofeifa Jorge ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 485 490

A five-years long study aiming to describe the basic genetic epidemiology of the dystrophinopathies in Costa Rica recruited 31 patients with clinical symptoms of DMD/BMD at the National Children’s Hospital (HNN). This center is the obligate reference hospital of the national health system for genetic diseases, however, the geographic origin of the patients, a low percentage of deletions and a high proportion of de novo mutations found among them indicate that a significant ascertainment bias impedes a substantial scientific approach to confront and alleviate the problems posed by these severe diseases in Costa Rica. Rev. Biol. Trop. 52(3): 485- 490. Epub 2004 Dic 15.

Un estudio de cinco años tendiente a describir la epidemiología genética básica de las distrofinopatías en Costa Rica detectó 31 pacientes con sintomatología de DMD o de BMD en el Hospital Nacional de Niños (HNN), el centro de referencia del sistema nacional de salud para enefrmedades hereditarias, sin embargo, la distribución geográfica de los pacientes, un bajo porcentaje de deleciones y una muy elevada proporción de mutaciones de novo indican que un significante sesgo de averiguación impide el estudio científico de riguroso tendiente a disminuir el impacto de estas enfermedades en Costa Rica.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300010 Las mutaciones inestables, nuevo reto para el consejo genético de enfermedades hereditarias Cuenca Patricia Morales Fernando ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 491 499

Unstable mutations, new challenges for genetic counseling of inherited disorders. Unstable mutations or amplification of DNA tandem repeats sequences constitute a new kind of genetic alteration discovered in the 90´s that cause hereditary diseases. This mutation has been found inside or near important genes involved in the normal neurological function in human beings. In some cases, the presence of the amplification causes altered expression of the genes, their inactivation or the synthesis of a protein with new functions. Some common characteristics of these diseases are that they affect the central nervous system and are degenerative in nature. Most of them show genetic anticipation meaning that the severity of the manifestations increases in each generation and appear at an earlier age. In most cases, the severity of the symptoms is positively correlated with the size of the amplification. Twenty illnesses caused by this kind of mutations have been identified so far. Briefly, this work reviews the current knowledge about this topic. Rev. Biol. Trop. 52(3): 491-499. Epub 2004 Dic 15.

Las mutaciones inestables constituyen un tipo de alteración genética descubierta en la década de los noventa. En condiciones normales, regiones específicas de los genes están constituidas por repeticiones de una secuencia corta que puede ser de tres, cuatro, cinco o más nucleótidos; por ejemplo CAG, CGG, ATTCT, etc. Este nuevo tipo de mutación consiste en un aumento en la cantidad de éstas repeticiones, lo que causa una alteración en la expresión de dichos genes. Son inestables porque se ha observado que el tamaño de la secuencia repetida varía cuando las células se dividen por mitosis o meiosis, lo cual tiene implicaciones sobre la herencia y por consiguiente sobre el consejo genético que debe brindarse a los afectados. Estas mutaciones se han encontrado en genes importantes para la función neurológica normal del ser humano, donde pueden alterar el transporte de los ARN desde el núcleo al citoplasma, provocar la inactivación del gen o producir una proteína con funciones nuevas. La mayoría de las enfermedades causadas por estas mutaciones afectan el sistema nervioso, son degenerativas y presentan el fenómeno de anticipación genética, es decir que los afectados dentro de una familia se enfermarán más jóvenes y en forma más severa con el paso de las generaciones. La cantidad de repeticiones de la secuencia repetida presenta una correlación negativa con la edad de manifestación, así como una correlación positiva con la severidad de la enfermedad. En este momento existen veinte padecimientos identificados que son causados exclusivamente por este tipo de mutación. Este trabajo es una breve revisión actualizada del tema.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300011 Disabilities caused by unstable mutations in Costa Rica Cuenca Patricia Morales Fernando Castro Isabel ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 501 505

Myotonic dystrophy and fragile X syndrome are two genetically determined relatively common disabilities. Both are examples of a new type of mutation mechanism called unstable or dynamic mutations, triple repeats expansions or DNA amplification. Fragile X syndrome is recognized as the main cause of hereditary mental retardation and myotonic dystrophy is considered the most common muscular dystrophy of adults. This is a prospective non randomized study of clinically affected people, in order to confirm the diagnosis with molecular techniques (Southern blot and PCR) and to perform cascade screening of the rest of the family to offer them adequate genetic counseling. We were able to corroborate the initial diagnosis in most clinical cases of myotonic dystrophy, but in the cases of mental retardation more than half studies were negative for fragile X syndrome, stressing the difficulties encountered by medical practitioners to diagnose this syndrome. The reasons for this are several; probable the main culprit is the subtle and unspecific clinical picture affected individuals exhibit, particularly children before puberty. Cascade screening, genetic counseling and selective abortion are the only tools available to prevent these disabling diseases for the moment. Rev. Biol. Trop. 52(3): 501-505. Epub 2004 Dic 15.

La distrofia miotónica tipo1 (DM1) y el síndrome del cromosoma X frágil (FRAXA) son dos enfermedades hereditarias relativamente comunes. Ambas constituyen ejemplos de un nuevo tipo de mecanismo mutacional, llamado mutaciones inestables o dinámicas, expansión de tripletas, o amplificación del ADN. La DM1 se considera como la distrofia muscular más frecuente en los adultos y FRAXA es la principal causa de retardo mental hereditario. Este trabajo presenta resultados actualizados de un estudio prospectivo no aleatorio en pacientes clínicamente afectados, que se realiza con el objetivo de confirmar el diagnóstico con técnicas moleculares (Hibridación de Southern y reacción en cadena de la polimerasa, PCR), y llevar a cabo el tamizaje en cascada del resto de la familia para ofrecerles consejo genético adecuado. Se confirmó el diagnóstico clínico inicial en la mayoría de los casos de distrofia miotónica, pero en los casos con retardo mental, más de la mitad de los análisis resultaron negativos para la amplificación en el gen FMR1, específica de FRAXA. La razón principal para esto podría ser el cuadro clínico muy sutil que muestran los niños afectados antes de la pubertad. Los únicos métodos disponibles para prevenir estas discapacidades por el momento son, el tamizaje en cascada, el consejo genético y el aborto selectivo. De los cuales, el último no se puede llevar a cabo según las leyes vigentes en Costa Rica.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300012 Glaucoma in Costa Rica: Initial approaches Chavarría-Soley Gabriela Rautenstrauss Bernd Azofeifa Jorge ,Friedrich-Alexander-Universität Erlangen-Nürnberg Germany ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 507 520

Glaucoma is the second most frequent cause of irreversible blindness worldwide. Genetic factors have been implicated in the development of the disease. So far six loci (GLC1A-GLC1F) and two genes (TIGR/MYOC and OPTN) are involved in the development of juvenile (JOAG) and adult onset or chronic primary open angle glaucoma (COAG), while two loci (GLC3A,GLC3B) and one gene (CYP1B1) are known for primary congenital glaucoma (PCG). Here we summarize the results of the first genetic studies of glaucoma in Costa Rica. Nine families: 1 with JOAG, 1 with PCG and 7 with COAG were screened for mutations at the known genes. A10 bp duplication, 1546-1555dupTCATGCCACC, at the CYP1B1 gene, causes, in homozygous state, glaucoma in the consanguineous PCG family. This mutation has been found in different countries and generates an early stop codon that termitates protein synthesis 140 amino acids earlier than the normal allele. In exon 1 of the TIGR/MYOC the innocuous Arg76Lys variant was found in two of the COAG families. In the OPTN gene two variants in the coding region (Thr34Thr, Met 98Lys) and 7 intronic changes were found in other Costa Rican glaucoma patients. One of the COAG families was chosen for a genome scan with 379 microsatellite markers and linkage analysis. LOD scores "suggestive" of linkage were obtained for several chromosomal regions. Evidence indicates that hereditary glaucoma in Costa Rica is highly heterogeneous and that further studies in the country will probably disclose some up to now unknown genes responsible for the disease. Rev. Biol. Trop. 52(3): 507-520. Epub 2004 Dic 15.

El glaucoma es la segunda causa de ceguera irreversible en el mundo. El componente genético de algunos de los distintos tipos ha sido demostrado: seis loci (GLC1A-GLC1F) y dos genes (TIGR/MYOC y OPTN) se conocen, hasta ahora, como responsables de la aparición de glaucomas primarios de ángulo abierto tanto del tipo juvenil (JOAG) como de l tipo de adultos (COAG). Además, dos loci (GLC3A,GLC3B) y un gene (CYP1B1) se han descubierto como causas del tipo primario congénito (PCG). Se presenta una relación de los estudios genéticos iniciales sobre el glaucoma en Costa Rica. Nueve familias: 1 con JOAG, 1 con PCG y 7 con COAG se estudiaron en busca de mutaciones en los genes conocidos. Una duplicación de 10 pb, 1546-1555dupTCATGCCACC, en el gene CYP1B1, causa glaucoma en condición homocigota en una familia consaguínea con PCG. Esta mutación se ha encontrado en otros países y origina un codón de terminación prematuro que codifica una proteína 140 aminoácidos más corta que la normal. En dos de las familias con COAG se encontró una variante inocua Arg76Lys en el exón 1 del gen TIGR/MYOC. Otros pacientes presentaron, en el gene OPTN, dos variantes en la region codificante (Thr34Thr, Met 98Lys) y 7 cambios intrónicos. Una de las familias con COAG cumple con los requerimientos mínimos para un análisis de ligamiento, por lo que se utilizaron 379 marcadores microsatelíticos para mapear el gen causante de la enfermedad. No se obtuvieron valores LOD que claramente implicaran a alguna región cromosómica. La evidencia señala que el glaucoma hereditario en Costa Rica tiene una gran heterogeneidad genética y que es muy posible que los estudios que se desarrollan vayan a descubrir nuevos genes involucrados en la patología.

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Genet 2003 121 Wiltshire S Hattersley A.T Hitman G.A Walker M Levy J.C Sampson M O’Rahilly S Frayling T.M Bell J.I Lathrop G.M Bennet A Dhillon R Fletcher C Groves C.J Jones E Prestwich P Simecek N Rao P.V.S Wishart M Foxon R Howell S Smedley D Cardon L.R Menzel S McCarthy M.I A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q Am. J. Hum. Genet 2001 69 Wirtz M.K Samples J.R Kramer P.L Rust K Topinka J.R Yount J Koler R.D Acott T.S Mapping of gene for adult-onset primary open-angle glaucoma to chromosome 3q Am. J. Hum. Genet 1997 60 Wirtz M.K Samples J.R Rust K Lie J Nordling L Schilling K Acott T.S Kramer P.L GLC1F, a new primary open-angle glaucoma locus, maps to 7q35-q36 Arch. Ophthalmol 1999 117 Wolfs R.C.W Klaver C.C.W Ramrattan R.S van Duijn C.M Hofman A de Jong P.T.V.M Genetic Risk of Primary Open-angle Glaucoma Opht. Mol. Genet 1998 116 Aung T Ebenezer N.D Brice G Child A.H Prescott Q Lehmann O.J Hitchings R.A Bhattacharya S.S Prevalence of optineurin sequence variants in adult primary open angle glaucoma: implications for diagnostic testing J. Med. GenetPrevalence of optineurin sequence variants in adult primary open angle glaucoma: implications for diagnostic testing 2003 408 Online Mendelian Inheritance in man Online Mendelian Inheritance in man 2004 Baltimore Johns Hopkins University National Center for Biotechnolgy Information National Center for Biotechnolgy Information 2004 U.S. National Library of Medicine
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300013 Molecular diagnosis of hemophilia A and B. Report of five families from Costa Rica Salazar-Sánchez Lizbeth Jiménez-Cruz Guillermo Chaverri Pilar Schröder Winnie Wulff Karin Jiménez-Arce Gerardo Sandoval Miriam Ramírez Patricia Herrmann F.H ,Universidad de Costa Rica San José Costa Rica ,Hospital México San José Costa Rica ,Ernst-Moritz-Arndt-University Greifswald Germany 09 2004 2004 52 521 530

Hemophilia Aand B are X-chromosome linked bleeding disorders caused by deficiency of the respective coagulation factor VIII and IX. Affected individuals develop a variable phenotype of hemorrhage caused by a broad range of mutations within the Factor VIII or Factor IX gene. Here, were report the results of the molecular diagnosis in a five Costa Rican families affected with Hemophilia. Methods of indirect and direct molecular diagnosis are applied in three Hemophilia A and two Hemophilia B families from Costa Rica as well as preconditions, practicability and facilities of this diagnosis. In two families with Hemophilia A and both families with Hemophilia B the causative mutation could be detected by Southern blotting, polymerase chain reaction or sequence analysis. One Hemophilia A family could only analyzed by linkage analysis using genomic markers. Rev. Biol. Trop. 52(3): 521-530. Epub 2004 Dic 15.

La hemofilia A y B es una enfermedad hemorrágica hereditaria ligada al cromosoma X, producida por la deficiencia del factor VIII o IX, respectivamente. Los individuso afectados presentan un fenotipo de hemorragia variable causada por el amplio espectro de mutacionesdentro del gen del factor VIII o IX. Se reportan los resultados preliminares del diagnóstico molecular de familias hemofilicas costarricenses. Se demuestran los hallazgos obtenidos por medio de diagnóstico molecular directo e indirecto en tres familias con hemofilia A y dos con hemofilia B; así como las precondiciones y facilidad de este diagnóstico. En dos familias con hemofilia A y dos con hemofilia B, la mutación responsable pudo ser detectada por medio de Southern Blot, por la reacción en cadena de la polimerasa o por secuenciación genética. Una familia con hemofilia A pudo ser analizada solamente por medio de análisis indirecto por medio de marcadores genéticos intragénicos y extragénicos.

 Hemophilia A Hemophilia B factor IX factor VIII molecular diagnosis carrier detection Hemofilia A Hemofilia B factor IX factor VIII diagnóstico molecular detección de portadores Ahrens P Kruse T.A Schwarty M Rasmussen P.B Din N A new HindIII restriction fragment length polymorphism in the Hemophilia A locus Hum. Genet 1987 76 Chan V Tong T.N Chan T.P Multiple XbaI polymorphisms for carrier detection and prenatal diagnosis of haemophilia A Br. J. Haematol 1989 73 Chistolini A Papacchini M Mazzucconi M.G La Verde G Arcieri R Ferrari A Paesano R Pachi A Mariani G Carrier detection and prenatal diagnosis in Haemophilia A and B Hematology 1990 75 Forbes C.D Aledort L.M Madhok R Hemophilia Hemophilia 1997 London Chapman Hall Medical Furie B Furie B Hemophilia basis of Hemophilia Sem. Hematol 1990 27 Giannelli F Anson D.S Choo K.H Ress D.J Einship P.R Ferrari N Rizza C.R Brownlee G.G Characterization and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency) Lancet 1984 1 ^s8371 Gitschier J Wood W.I Goralka T.M Wion K.L Chen E.Y Eaton D.H Vehar G.A Capon D.J Lawn R.M Characterization of the human factor VIII gene Nature 1984 312 Harper K Pembrey M.E Winter R.M Hartley D Tuddenham E.G.D A clinically useful DNA probe closely linked to haemophilia A Lancet 1984 2 8393 Herrmann F.H Scharrer I Humangenetische Beratung bei Hämophilie A und B Mitteilungen der Deutschen Hämophiliegesellschaft zur Bekämpfung von Blutungskrankheiten Mitteilungen der Deutschen Hämophiliegesellschaft zur Bekämpfung von Blutungskrankheiten 1999 Hamburg Herrmann F.H Wehnert M Schröder W Wulff K Genomic diagnosis of Hemophilia A and B Thromb. Haemorrh. Disorders 1990 2 1 Herrmann F.H Wulff K Molekulare Genanalyse und Geniagnostik bei Hämophilie B und FVII Mangel Hämostaseologie 1998 3 Costa Rica: estimaciones y proyecciones de población actualizadas al año 2000. Período 1970- 2050 Costa Rica: estimaciones y proyecciones de población actualizadas al año 2000. Período 1970- 2050 San José Instituto Nacional de Estadística y Censos y Centro Centroamericano de Población, Universidad de Costa Rica Kogan S.C Doherty M Gitschier J An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to Hemophilia A N. Engl. J. Med 1987 317 Lakich D Kazazian H Antonarakis S.E Gitschier J Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A Nature Genet 1993 5 Miller S.A Dykes D.D Polesky H.F A simple salting out procedure for extracting DNA from human nucleated cells Nucleic Acid Res 1988 16 Oberle I Camerino G Heilig R Grunebaum L Cazenave J.P Crapanzano C Mannucci P.M Mandel J.L Genetic screening for haemohilia A with a polymorphic DNA probe N. Engl. J. Med 1985 312 Pattinson J.K Millar D.S McVery J.H Grundy C.B Wieland K Misbashan R.S The molecular genetic analysis of Hemophilia A: A directed search strategy for the detection of point mutation in the human factor VIII gene Blood 1990 76 Peake I Registry of DNA Polymorphisms within or close to the Human Factor VIII and IX Genes Thromb. Haemost 1992 67 Wehnert M Schröder W Herrmann F.H Two new markers at DXS 115 useful for genomic diagnosis in haemophilia A Thromb. Haemorrh. Disorders 1991 3 1 Wehnert M Shukova E.L Surin V.I Schroder W Gya Solovjev Herrmann F.H Prenatal diagnosis of haemophilia by the polymerase chain reaction using the intragenic Hind III polymorphism Prenatal Diagnosis 1990 10 Winship P.R Anson D.S Rizza C.R Brownlee G.G Carrier detection in haemophilia B using two futher intragenic restriction fragment length polymorphisms Nucleic Acid Res 1984 12 Winship P.R Rees D.J Alkan M Detection of polymorphisms at cytosine phosphoguanadine dinucleotides and diagnosis of haemophilia B carriers Lancet 1989 18639 Wion K.L Tuddenham E.G.D Lawn R.M A new polymorphism in the factor VIII gene for prenatal diagnosis of haemophilia A Nucleic Acid Res 1986 14 Wulff K Bykowska K Lopaciuk S Herrmann F.H Molecular analysis of Hemophilia B in Poland: 12 novel mutations of the factor IX gene Acta Biochim. Polonica 1999 Wulff K Ebener U Wehnert Ch-S Ward P.A Reuner U Hiebsch W Herrmann F.H Wehnert M Direct molecular genetic diagnosis and heterozygote identification in X-linked Emery-Dreifuss muscular dystrophy by heterodeplex analysis Dis. Markers 1997 13 Wulff K Schröder W Wehnert M Herrmann F.H Twenty-five novel mutations of the factor IX gene in haemophilia B Human Mutat 1995 6 Wulff K Schröder W Wehnert M Herrmann F.H Scharrer I.III Schramm W Molecular Analysis of Hemophilia B: Greifswald Registry FIX deficiency (HemophiliaB) 2003 Hemophilia Symposium Hamburg 2001 Springer Berlin Yoshitake S Schach B.G Foster D.C Davie E.W Kurachi K Nucelotide sequence of the gene of human factor IX ( haemophilic factor B) Biochem 1985 24
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300014 Familial Breast Cancer in Costa Rica: An Initial Approach Ramírez Monge Adriana Gutiérrez-Espeleta Gustavo A Loáiciga Vega Kenneth ,Universidad de Costa Rica ,Universidad de Costa Rica ,Hospital San Juan de Dios San José Costa Rica 09 2004 2004 52 531 536

Cancer is a worldwide problem because of its high rates of incidence and associated mortality. By 2000, more than 6.2 million people died from this illness worldwide. Among all types of cancer, breast cancer is one of the most studied. Each year, one million new cases are diagnosed around the world. We can classify breast cancer into two main kinds: sporadic cases and those which are a product of inherited genetic alterations. Approximately 5-10% of breast cancer cases are the result of inherited mutations, or alterations in breast cancer susceptibility genes, BRCA1 and BRCA2. Like other countries, Costa Rica possesses high rates of incidence and mortality for breast cancer. According to the "Registro Nacional de Tumores" (National Office of Tumor Records), in 2000 breast cancer had the highest rate of incidence and in 2002 it had the highest rate of mortality in comparison to other types of cancer. For this reason and the generalized lack of knowledge in the field we conducted an epidemiological research on breast cancer patients from Hospital San Juan de Dios, San José, Costa Rica, to find families with a history of breast cancer, and to determine the occurrence of familial cases within the population studied. So far, we have found 23 families, within which we discovered very informative cases that have rendered the identification of a pattern of inheritance. These findings allow us to announce that in Costa Rica there are several cases of inherited breast cancer and that we need more research is needed to improve the prevention, control, and treatment of this disease. Rev. Biol. Trop. 52(3): 531-536. Epub 2004 Dic 15.

El cáncer es un problema a nivel mundial porque posee altas tasas de incidencia y mortalidad. Para el año 2000 más de 6.2 millones de personas murieron a causa de esta enfermedad. El cáncer de mama es uno de los tipos de cáncer más estudiados en el mundo por las mismas razones. Cada año, se diagnostican más de un millón de casos nuevos de cáncer de mama alrededor del mundo. Podemos clasificar al cáncer de mama en dos tipos principales: los casos esporádicos y los que son producto de alteraciones genéticas heredables. De todos los casos que son diagnosticados en la población, aproximadamente de un 5 a un 10 % son resultado de mutaciones heredadas o alteraciones en los genes de susceptibilidad BRCA1 y BRCA2. Como en otros países, Costa Rica posee altas tasas de incidencia y mortalidad para el cáncer de mama. Según el Registro Nacional de Tumores para el año 2000 el cáncer de mama tuvo la tasa de incidencia más alta y para el 2002 alcanzó la tasa de mortalidad más alta en comparación con otros tipos de cáncer. Por esta razón y por la falta de conocimiento existente decidimos realizar un estudio epidemiológico de los pacientes con cáncer de mama del Hospital San Juan de Dios para encontrar familias con un historial de cáncer de mama y determinar la existencia de casos de cáncer de mama familiares en esta población. Hemos encontrado 23 familias dentro de las cuales hayamos casos informativos que nos han permitido identificar un patrón de herencia. Estos hallazgos nos permiten afirmar que en Costa Rica se dan casos de cáncer de mama heredados y que necesitamos más investigación para mejorar el tratamiento de los pacientes que sufren de cáncer de mama.

 breast cancer incidence mortality epidemiology Costa Rica Cáncer de mama incidencia mortalidad epidemiología Costa Rica Breast Cancer Facts and Figures 2003- 2004 Breast Cancer Facts and Figures 2003- 2004 2003 American Cancer Society Cancer Facts and Figures 2004 Cancer Facts and Figures 2004 2004 American Cancer Society Aguilar M Manejo de los estadíos I y II del cáncer de mama entre los años 1990-1998 en el servicio de oncología del hospital San Juan de Dios Manejo de los estadíos I y II del cáncer de mama entre los años 1990-1998 en el servicio de oncología del hospital San Juan de Dios 1999 Bartels Rodríguez R Vargas R.M Muñoz G Incidencia y mortalidad del cáncer en Costa Rica 1994/1996 Incidencia y mortalidad del cáncer en Costa Rica 1994/1996 1999 San José Ministerio de Salud Chen C Weiss N Newcomb P Barlow W White E Hormone replacement therapy in relation to breast cancer JAMA 2002 287 Eastson D.F Ford D Bishop T Breast and ovarian cancer incidence in BRCA1-mutations carriers Am. J. Hum. Genet 1995 56 Friedwald V Buzdar A BoKulich M Cáncer de seno todo lo que usted debe saber Cáncer de seno todo lo que usted debe saber 1997 Bogotá Grupo editorial Norma Haber D Fearon E The promise of cancer genetics Lancet 1998 351 Hadjisavvas A Charalambous E Adamou A Chistodolou C Kyriacou K BRCA2 Germline mutations in Cypriot patients with familial Breast/Ovarian Cancer Hum. Mut 2003 21 Lawrence W Peshkin B Liang W Isaacs C Lerman C Mandelblatt J Cost of Genetic counseling for BRCA1 and BRCA2 Breast cancer susceptibility Mutations Can. Epidemiol. Biomak. Prev 2001 10 Llort G Yagüe C Peris M Blanco G Dermà J Bale A Alvarez M Low frequency or recurrent BRCA1 and BRCA2 Mutation in Spain Hum. Mut 2002 19 McPhearson K Steel C Dixon J Breast cancer-epidemiology, risk factors and genetics Brit. Med. J 2000 321 Peterson E Milliron K Lewis K Goold S Merajver S Health insurance and discrimination concerns and BRCA1/2 in a clinic population Can. Epidemiol. Biomak. Prev 2002 11 Ruiz P Sinilnikova O Badzioch M Calderon A Chopin S Fabrice O Gonzáles J Szabo C Lenoir G Goldgar D Barrera H BRCA1 and BRCA2 Mutation Analysis of Early onset and familial breast cancer cases in Mexico Hum. Mut 2002 20 Sierra R Rosero-Bixby L Antich D Muñoz G Cáncer en Costa Rica: Epidemiología Descriptiva Cáncer en Costa Rica: Epidemiología Descriptiva 1995 San José Universidad de Costa Rica Wooster R Neuhausen S Mangion J Localization of breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13 Science 1994 256 Global cancer rates could increase by 50% to 15 million by 2020 Global cancer rates could increase by 50% to 15 million by 2020 2003 World Health Organization Márquez A Trujillo R Cáncer de mama hereditario (I) MEDSPAIN. La nueva revista de Medicina y Salud en InternetCáncer de mama hereditario (I) 1999 Márquez A Trujillo R Cáncer de mama hereditario (II) MEDSPAIN. La nueva revista de Medicina y Salud en InternetCáncer de mama hereditario (II) 1999
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300015 Pasado, presente y futuro de la citogenética en Costa Rica Castro Volio Isabel ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 537 544

Past, present and future of cytogenetics in Costa Rica. This is an overview of the past, present and future of human Cytogenetics in Costa Rica. It started in 1965 at the University of Costa Rica where it has been developed slowly but steadily. There is only one overloaded clinical cytogenetic laboratory in the social security system. The tests currently performed are peripheral blood and blood marrow karyotypes, prenatal cytogenetic diagnosis (amniotic fluid and fetal blood) and less frequently skin biopsies. The task now is to standardize molecular cytogenetic techniques, we are actually working with PRINS in order to study submicroscopic subtelomeric rearrangements associated with mental retardation and other microdeletion syndromes as well. Rev. Biol. Trop. 52(3): 537-544. Epub 2004 Dic 15.

Esta es una breve descripción de lo que ha sido el desarrollo de la citogenética humana en Costa Rica, la situación actual y las expectativas a corto plazo. Esta ciencia- arte nació hace poco más de cuarenta años en la Facultad de Medicina de la Universidad de Costa Rica. Actualmente se desarrolla como un servicio diagnóstico-asistencial en el Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera" y con un componente adicional de investigación en el Instituto de Investigaciones en Salud de la misma universidad. Los ensayos que se ofrecen a la población son los cariotipos en sangre periférica y en médula ósea, el diagnóstico prenatal citogenético en muestras de líquido amniótico y de sangre fetal y con menos frecuencia en biopsias de piel.

 Cytogenetics karyotypes human genetics Costa Rica Citogenética cariotipos genética humana Costa Rica Análisis de la situación de la salud, documento preliminar, Mortalidad infantil por grupo de causas. Costa Rica, Período 1970-1994 Análisis de la situación de la salud, documento preliminar, Mortalidad infantil por grupo de causas. Costa Rica, Período 1970-1994 1996 INCIENSA/ MS Porcentaje de la mortalidad por anomalías congénitas con respecto al total de defunciones infantiles, Costa Rica 1990-1997 Porcentaje de la mortalidad por anomalías congénitas con respecto al total de defunciones infantiles, Costa Rica 1990-1997 1998 Dirección General de Estadística y Censos y Ministerio de Salud, Departamento Centro de Información, Sección Otros Programas Prioritarios Bonifacio S Centrone C Da Prato L Scordo M.R Estienne M Torricelli F Use of primed in situ labelling (PRINS) for the detection of telomeric deletions associated with mental retardation Cytogenet. Cell Genet 2001 93 Castro R Ramírez V Cuenca P Análisis de micronúcleos y otras anormalidades nucleares en el epitelio oral de mujeres expuestas ocupacionalmente a plaguicidas Rev. Biol. Trop 2004 52 3 Castro I Jiménez J Diagnóstico prenatal de aberraciones cromosómicas en Costa Rica Rev. Méd. Hosp. Nal. Niños (Costa Rica) 1985 20 Castro I Cuenca P Tamizaje de sitio frágil en el cromosoma X en una población de retardados mentales: Hallazgos preliminares Rev. Méd. Hosp. Nal. Niños (Costa Rica) 1987 1 Castro I Montero C Jiménez G Características cromosómicas asociadas con leucemias y otras hematopatías en Costa Rica Rev. Biol. Trop 1993 41 Castro I Escalante G Mora H Guerra D Sánchez L Peña C Cariotipo de células fetales en el diagnóstico prenatal en Costa Rica Rev. Biol. Trop 1995 43 Castro Volio I Cuenca Berger P Frecuencia del síndrome del cromosoma X frágil en la Escuela de Enseñanza Especial "Fernando Centeno Güell" Acta Ped. Cost 1996 10 Castro Volio I Sander Mangel K Vargas Prado M Sánchez Cháves L Escalante López G Cariotipos fetales en embarazos de alto riesgo genético provenientes de hospitales de la seguridad social y de la consulta privada, de 1993 a 1998 Acta Méd. Cost 2000 42 Castro Volio I Sander Mangel K Vargas Prado M Sánchez Cháves L Escalante López G Diagnóstico prenatal citogenético mediante amniocentesis durante los trimestres II y III de gestación en Costa Rica Rev. Biol. Trop 2001 49 Castro-Volio I Valle-Bourrette L Chromosomal defects in 34 male homosexuals, half of them with HIV antibodies Rev. Biol. Trop 2002 50 1 Castro Volio I Ortiz Morales F Cariotipos conyugales en infertilidad y pérdidas gestacionales en Costa Rica Toko-Gin Prac 2002 61 Castro Volio I Ortiz Morales F Cordocentesis para diagnóstico fetal citogenético en Costa Rica Progr. Diag. Trat. Prenat 2003 15 Castro Volio I El diagnóstico prenatal de defectos cromosómicos en Costa Rica Rev. Biol. Trop 2004 52 3 Cruz M Giovannetti A.E De Céspedes C Fernández R Relación entre síndrome de Down, edad materna y presencia de translocaciones cromosómicas Acta Méd. Cost 1983 26 Cuenca P Arias E Malformaciones congénitas en el Hospital Calderón Guardia: Frecuencia y estudio citogenético Rev. Med. Hosp. Nal. Niños (Costa Rica) 1985 20 Cuenca P Recién nacidos con malformaciones congénitas, citogenética y aspectos epidemiológicos: Hospital Dr. Rafael Angel Calderón Guardia, 1982- 1983 Recién nacidos con malformaciones congénitas, citogenética y aspectos epidemiológicos: Hospital Dr. Rafael Angel Calderón Guardia, 1982- 1983 1986 Cuenca P Untersuchung chromosomaler heteromorphismen bei unterschiedlichen ethnischen Gruppen Costa Ricas und ihre Bedeutung fur die Populationsgenetik Untersuchung chromosomaler heteromorphismen bei unterschiedlichen ethnischen Gruppen Costa Ricas und ihre Bedeutung fur die Populationsgenetik 1992 Cuenca P Ramírez V Castro R Schosínsky K Efectos genotóxicos de los pesticidas en una población costarricense con exposición ocupacional: Micronúcleos de linfocitos y mucosa oral, aberraciones cromosómicas, mecanismos de reparación y electroforesis de células únicas, controlando paralelamente los niveles de colinesterasa sérica y eritrocítica. Informe final ante PLAGSALUD/OPS Efectos genotóxicos de los pesticidas en una población costarricense con exposición ocupacional: Micronúcleos de linfocitos y mucosa oral, aberraciones cromosómicas, mecanismos de reparación y electroforesis de células únicas, controlando paralelamente los niveles de colinesterasa sérica y eritrocítica. Informe final ante PLAGSALUD/OPS 1997 Cuenca P Morales F Las mutaciones inestables, nuevo reto para el consejo genético de enfermedades hereditarias Rev. Biol. Trop 2004 52 3 Handal N Matamoros M.C Cruz M.E Barrantes R Estudio de sitios frágiles cromosómicos en una población de esquizofrénicos de Cartago, Costa Rica Acta Méd. Cost 1988 31 Knight S. J Flint J Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis J. Med. Genet 2000 37 Rivera J Cruz F Saborío M Sesín O Trisomía 18 Rev. Med. Hosp. Nal. Niños (Costa Rica) 1981 16 Rivera J Saborío M Cruz F Un síndrome cromosómico poco frecuente: trisomía 22 Rev. Med. Hosp. Nal. Niños (Costa Rica) 1984 19 Salazar L Vázquez L.F Rivera J Venegas P Estudio citogenético en médula ósea de 26 casos de leucemia mieloide crónica en pacientes del Hospital San Juan de Dios Rev. Cost. Cienc. Méd 1997 18 Sánchez M.A Venegas P Rivera J Hallazgo de una deleción en el brazo largo del cromosoma 22 en un paciente con problemas de lenguaje Rev. Med. Hosp. Nal. Niños (Costa Rica) 1995 30 Sánchez M.A Venegas P Inversión paracéntrica en el brazo corto del cromosoma 1, en un paciente con problemas de obesidad y aprendizaje Rev. Med. Hosp. Nal. Niños (Costa Rica) 1996 31 Solís V Aspectos genéticos en la patología de las leucemias: Monografía Aspectos genéticos en la patología de las leucemias: Monografía 1977 a Bucarest Universidad de Bucarest Solís V Métodos de bandeo y su aplicación en el estudio de las aberraciones cromosómicas: Monografía Métodos de bandeo y su aplicación en el estudio de las aberraciones cromosómicas: Monografía 1977 b Bucarest Universidad de Bucarest Solís V Estudio comparativo de las modificaciones cromosómicas en diferentes tipos de proliferaciones malignas (humanas y experimentales) Estudio comparativo de las modificaciones cromosómicas en diferentes tipos de proliferaciones malignas (humanas y experimentales) 1978 Solís V Estudio citogenético del tumor ascítico Guerin T8 después de diez años de pasajes en serie, utilizando hospederos homólogos Acta Méd. Cost 1982 25 Solís V Reaparición de una translocación no común implicada en la formación del cromosoma Philadelphia (Ph¹ ) Acta Méd. Cost 1983 26 Solís V Estudio citogenético de un caso de leucemia crónica linfocítica de células T Acta Méd. Cost 1984 27 Solís V Patrón de las asociaciones satelíticas en mujeres post-parto y en neonatos Rev. Biol. Trop 1985 33 Solís V Pritchard J Cowell J Cytogenetic changes in Willms’ tumours Canc. Genet. Cytogenet 1988 34 Solís V Alvarado M. de los A Ruiz E Carrillo J Navarrete M Sánchez G Jiménez E Citogenética y citoquímica de pacientes con leucemia en dos hospitales neotropicales Rev. Biol. Trop 2000 48 Solís V Bandeo de cromosomas humanos utilizando extracto crudo de frutas u hojas de papaya Rev. Biol. Trop 2001 49 Venegas P Rivera J Estudios citogenéticos en niños con leucemia linfocitica aguda-B en Costa Rica Rev. Biol. Trop 2004 52 3 Venegas P Fallas A.V Rivera J Sánchez M.A Frecuencia del síndrome del X frágil en la consulta de Genética Médica del Hospital Nacional de Niños Rev. Méd. Hosp. Nal. Niños (Costa Rica) 1997 32 Venegas P Sánchez M.A Rivera J Hallazgo de una translocación 1;16 en una paciente con aparente fenotipo de síndrome de Down Acta Ped. Cost 1997 11 Yock A J Contribución al estudio de las anormalidades de los cromosomas humanos Contribución al estudio de las anormalidades de los cromosomas humanos 1965
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300016 El diagnóstico prenatal de defectos cromosómicos en Costa Rica Castro Volio Isabel ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 545 549

Prenatal diagnosis of chromosomic defects in Costa Rica. This is an historical overview of prenatal cytogenetic diagnosis in Costa Rica. It started in 1984 at the Institute for Health Research of the University of Costa Rica. This is the only fetal cytogenetic diagnosis facility in the country and serves social security as well as private patients. Perinatologists send amniotic fluid and fetal blood samples from high risk pregnancies, mainly due to abnormal ultrasound assessment, sonographic markers of aneuploidy and advanced maternal age. Second and third trimester diagnosis allows the development of coping strategies for the families of affected fetuses, since pregnancy interruption is not permitted. Normal fetal cytogenetic results provide reassurance to the parents. Rev. Biol. Trop. 52(3): 545-549. Epub 2004 Dic 15.

Esta es una breve reseña histórica del diagnóstico prenatal citogenético en Costa Rica. Se realiza únicamente en el Instituto de Investigaciones en Salud de la Universidad de Costa Rica desde el año 1984. Sirve a los hospitales de la seguridad social y a la medicina privada. Trabajamos con muestras de líquido amniótico y de sangre fetal enviadas por los perinatólogos, provenientes de embarazos de alto riesgo, ya sea por presentar alteraciones en el ultrasonograma, marcadores sonográficos de aneuploidía o edad materna avanzada, entre otras indicaciones menos frecuentes. El diagnóstico se realiza en el segundo y en el tercer trimestre de gestación. Como la interrupción del embarazo no es permitida, el personal médico y la familia se prepara con tiempo para recibir de la mejor manera al neonato afectado. En los casos de cariotipo normal, esta información alivia la preocupación de los padres.

 amniocentesis percutaneous umbilical cord sample prenatal diagnosis fetal karyotypes Costa Rica amniosentesis cordón umbilical diagnóstico prenatal cariotipos fetal genética humana Costa Rica WHO working group: Fetal diagnosis of hereditary diseases Bull. WHO 1984 62 Castro I Mata L El diagnóstico prenatal de trastornos genéticos Acta Méd. Cost. (Costa Rica) 1985 28 Castro I Jiménez J Diagnóstico prenatal de aberraciones cromosómicas en Costa Rica Rev. Méd. Hosp. Nac. Niños (Costa Rica) 1985 20 Castro I Escalante G Mora H Guerra D Sánchez L Peña C Cariotipo de células fetales en el diagnóstico prenatal en Costa Rica Rev. Biol.. Trop 1995 43 Castro Volio I Sander Mangel K Vargas Prado M Sánchez Cháves L Escalante López G Cariotipos fetales en embarazos de alto riesgo genético provenientes de hospitales de la seguridad social y de la consulta privada, de 1993 a 1998 Acta Med. Cost 2000 42 Castro Volio I Sander Mangel K Vargas Prado M Sánchez Cháves L Escalante López G Diagnóstico prenatal citogenético mediante amniocentesis durante los trimestres II y III de gestación en Costa Rica Rev. Biol. Trop 2001 49 Castro Volio I Ortiz Morales F Cordocentesis para diagnóstico fetal citogenético en Costa Rica Prog. Diag. Trat. Prenat 2003 15 Nadler H.L Gerbie A.B Role of amniocentesis in the intrauterine detection of genetic disorders N. Engl. J. Med 1970 282 Randolph L.M Gersen S Keagle M Prenatal cytogenetics The Principles of Clinical Cytogenetics. Humana The Principles of Clinical Cytogenetics. Humana 1999 ^eNueva Jersey Totowa Romero R Ghidini A Santolaya J Milunsky A Fetal blood sampling Genetic disorders and the fetus Genetic disorders and the fetus 1992 Baltimore^eMaryland Johns Hopkins Serr D.M Sachs L Danon M Diagnosis of sex before birth using cells from amniotic fluid Bull. Res. Coun. Israel E 1955 5B Verp M.S Gerbie A.B Amniocentesis for prenatal diagnosis Clin. Obstet. Gynecol 1981 24 Wald N.J Kennard A Hackshaw A McGuire A Antenatal screening for Down syndrome J. Med. Screen 1997 4
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300017 Estudios citogenéticos en niños con Leucemia Linfocitica Aguda-B en Costa Rica Venegas Patricia Rivera Julio ,Caja Costarricense del Seguro Social San José Costa Rica 09 2004 2004 52 551 558

Cytogenetic studies in children with Acute Lymphocitic Leukemia-B in Costa Rica. Chromosome analyses were performed on bone marrow of 177 pediatric patients with Acute Lymphocitic Leukemia at the "Hospital Nacional de Niños". The standard cytogenetic techniques now belongs to the panel of mandatory analyses performed at diagnosis of our acute leukemia patients and represent a major advantage to be effective and independent prognostic factors, essential for therapeutic choices. Cytogenetic results were achieved in 83% of the bone marrow samples: normal karyotypes represented 29% and abnormal karyotypes 71% with the follow distribution: t(9;22) 3%; t(1;19) 5%; t(4;11) 3%, Hyperdiploidy 39%; other chromosomal abnormalities 21%. Systematic cytogenetic analyses are essencial to define morpho-immunologic sub-types of leukemia and to detect new translocations that allows to understand hematopoiesis and leukemogenesis. Rev. Biol. Trop. 52(3): 551-558. Epub 2004 Dic 15.

Se realizaron análisis cromosómicos en médulas oseas de 177 pacientes con Leucemia Linfocítica Aguda. Las técnicas citogenéticas convencionales forman parte del panel obligatorio de análisis realizados como diagnóstico a los pacientes con leucemia y representan una gran ventaja por ser factores efectivos e independientes de pronóstico, escenciales para la elección terapeútica. Los resultados citogenéticos fueron alcanzados en 83% de las muestras de médula osea: los cariotipos nomales representaron el 29% y los cariotipos anormales el 71% con la siguiente distribución: t(9;22) 3%; t(1;19) 5%; t(4;11) 3%, hiperdiploidía 39%; otras anormalidades cromosómicas 21%. El análisis citogenético sistemático es escencial para definir los subtipos morfo-inmunológicos de leucemia, y para detectar nuevas translocaciones que conduzcan a la comprensión de la génesis de la leucemia

 Acute Lymphocytic leukemia cytogenetics chromosomal abnormalities prognostic factors Costa Rica Leucemia Linfocítica Aguda citogenética aberraciones cromosómicas factores pronósticos Costa Rica Andreasson P Hoglund M Bekassy A.N Garwicz S Heldrup J Mitelman F Johansson B Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias Eur. J. Haematol 2000 65 Alter D Mark H.F Cytgenetics study of a patient with acute lymphobalstic leukemia using GTG-banding and chromosome painting Exp. Mol. Pathol 2000 69 Bhatia S Sather H.N Heerema N.A Trigg M.E Gaynon P.S Robison L.L Racial and ethnic differences in survival of Children with acute lymphoblastic leukemia Blood 2002 100 Boomer T Varella-Garcia M McGavran L Meltesen L Olsen A.S Hunger S.P Detection of E2A translocation in leukemias via fluorecense in situ hibridization Leukemia 2001 15 Castro Volio I Montero C Jiménez G Características cromosómicas asociadas con leucemias y otras hematopatías en Costa Rica Rev. Biol. Trop 1993 41 Castro Volio I Pasado, presente y futuro de la citogenética humana en Costa Rica Rev. Biol. Trop 2004 52 Chaves-Villalobos M Jiménez-Arce G Sandí-Díaz M Polimorfismo del gen de la banda 3 eritrocítica en grupos étnicos de Costa Rica Rev. Biol. Trop 2004 52 3 Dower D The epidemiology of Acute promyelocitic Leukemia: Best Pract Res Clin Haematol 2003 16 Forestier E Johansson B Borgstrom G Kerndrup G Johansson J Heim S Cytogenetics finding in a population-based series of 787 childhood acute lymphoblastic leukemias from the Nordic Countries. The NOPHO Leukemia Cytogenetic study Group. Eur. J. Haematol 2000 64 Groupe Francais de Cytogenetique Hematologique: collaborative study of Karyotypes in childhood acute lymphoblastic leukemias Leukemia 1993 7 Gisselbrecht S Oncogenes and leukemia: history and perspectives Med. Sci. (Paris). 2003 19 Harrison C.J The detection and significance of chromosomal abnormalities in childhood acute lymphoblastic leukaemia 2001 15 Hyakuna N Kaneko Y Katano N Iwai T Nagata T Sakashita K Takeda O Tanaka A Azuma H Sekine I Fujimoto T Prognosis significance of chromosome análisis in childhood acute lymphoblastic leukemia Children s cancer and leukemia study group (CCLSG). 2000 41 An International Sytem for Human Cytogenetic Nomenclature An International Sytem for Human Cytogenetic Nomenclature 1995 Basel Karger Jarosova M Holzerova M Jedlickova K Mihal V Zuna J Stary J Pospisilova D Zemanova Z Trka J Blazek J Pikalova Z Indrak K Importance of using comparative genomic hybridization to improve detection of chromosomal changes in childhood acute lymphoblastic leukemia Cancer Genet. Cytogenet 2000 123 Jiménez Bonilla R Historia de la investigación de la leucemia en Costa Rica Rev. Biol. Trop 2004 52 Koning M Reichel M Marschalex R Haas O.A Strehl S A highly specific and sensitive fluorescence in situ hybridization assay for the detection of t(4;11)(q21;q23) and concurrent submicroscopic deletions in acute leukaemias Br. J. Haematol 2002 116 Kurzrock R Kantarjian H.M Druker B.J Talpaz M Philadelphia Chromosome-positive leukemias: from basic mechanisms to molecular therapeutics Ann. Intern. Med 2003 138 10 Maloney K McGavran L Murphy J Odom L Stork L Wei Q Hunger S TEL-AML1 fusion identifies a subset of children with standard risk acute lymphoblastic leukemia who have excellent prognosis when a treated with therapy that includes a single delayed intensification Leukemia 1999 13 Lu X.Y Harris C.P Cooley L Margolin J Steuber P.C Sheldon M Rao P.H Lau C.C The utility of spectral Karyoting in the cytogenetic analysis of newly diagnosed pediatric acute lymphoblastic leukemia Leukemia 2002 16 Ma S.K Wan T.S Chan L.C Cytogenetics and molecular genetics of Childhood leukemia Hematol. Oncol 1999 17 3 Martín Ramos M Fernández Martínez F Barreiro Miranda E Cytogenetic abnormalities in acute lymphoblastic leukemia An. Esp. Pediatr 2001 55 1 Martínez-Ramírez A Urioste M Contra T Cantalejo A Tavares A Portero J.A Lopez-Ibor B Bernacer M Soto C Cigudosa J.C Benitez J Fluoresence in situ hybridization study of TEL/ AMLfusion and other abnormalities involving TEL and AML genes: Correlation with Cytogenetic finding and prognostic value in children with acute lymphoblastic leukemia Haematologica 2001 86 Mathew S Rao P.H Dalton J Downing J.R Raimondi S.C Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia Leukemia 2001 15 Morera B Marín-Rojas R Barrantes R Análisis de varios marcadores genéticos clásicos en la población de Costa Rica Rev. Biol. Trop 2001 49 Morera B Marín-Rojas R Barrantes R Gene Admixture in the Costa Rican Population Ann. Hum. Genet 2003 67 Nordgren A Heyman M Sahlen S Schoumans J Soderhall S Nordenskjold M Blennow E Spectral Karyotyping and intephase FISH reveal abnormalities not detected by conventional G-banding. Implications for treatment stratification of Childhood acute lympholastic leukemia: detailed analysis of 70 cases Eur. J. Haematol 2002 68 Patel A.S Hawkins A.L Griffin C.A Cytogenetics and cancer Curr. Opin. Oncol 2000 12 Perez-Vera P Mujica-Sanchez M Carnevale A Rivera- Luna R Paredes R Martinez A Frias Cytogenetic in acute lymphoblastic leukemia in Mexican Children: an Institutional experience Arch. Med. Res 2001 32 Pui C.-H Crist W.M Look T Biology and Clinical Significance of Cytogenetic Abnormalities in Childhood Acute Lymphoblastic Leukemia Blood 1990 76 Raimondi S.C Roberson P.K Pui C.H Behm F.G Rivera G.K Hyperdiploid (47-50) acute lymphoblastic leukemia in children Blood 1992 79 Raimondi S.C Pui C.H Hancock M.L Behm F.G Filatov L Rivera G.K Heterogeneity of hyperdiploid (51-67) childhood acute lymphoblastic leukemia Leukemia 1996 10 Rubin C.M Le Beau M.M Cytogenetic abnormalities in childhood acute lymphoblastic leukemia Am. J. Pediatr. Hematol. Oncol 1991 13 Rutherford M.N Bayly G.R Matthews B.P Okuda T Dinjens W.M Kondoh H LeBrun D.P The leukemogenic transcription factor E2a-Pbx1 induced expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells Leukemia 2001 15 Sattler M Scheijen B Weisberg E Griffin J.D Mutated tyrosine Kinases as therapeutic targets in myeloid leukemia Adv. Exp. Med. Biol 2003 532 Secker-Walker L.M on behalf of the European 11q23 Worshop Partricipants: General Report on the European Union Concerted Action Workshop on 11q23 Leukemia 1998 12 Silva M.L Ornellas de Souza M.H Ribeiro R.C Land M.G Boulhosa de Azevedo A.M Vasconcelos F Otero L Vasconcelos Z Bouzas L.F Abdelhay E Cytogenetic Analyisis of 100 consecutive newly diagnosed cases of Acute Lymphoblastic Leukemia in Rio de Janeiro Cancer Genet. Cytogenet 2002 137 Smith M.A Ries L.A.G Gurney J.G Ross J.A Ries L.A.G Smith M.A Gurney J.G Linet M Tamra T Young J.L Bunin G.R Leukemia Cancer Incidence and Survival Among Children and Adoldescents: United States SEER Program 1975-1995 Cancer Incidence and Survival Among Children and Adoldescents: United States SEER Program 1975-1995 1999 Bethesda Md: Cancer Statistics Branch, Cancer Surveillance Research Program, Division of Cncer Control and Population Sciences, National Cancer Instituve Solís V Alvarado M. de los A Ruiz E Carrillo J Navarrete M Sánchez G Jiménez E Citogenética y citoquímica de pacientes con leucemia en dos hospitales neotropicales Rev. Biol. Trop 2000 48 Chromosome in Leukemia.Cromosomal Abnormalities in acute Lymphoblastic leukemia Cancer. Genet. Cytogenet 1981 4 Thirman M.J Gill H.J Burnett R.C Rearrengement of MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocatios N. Engl. J. Med 1993 329 Uckun F.M Sensel M.G Sather H.N Gaynon P.S Arthur D.C Lange B.J Steinherz P.G Kraft P Hutchinson R Nachman J.B Reaman G.H Heerema N.A Clinical Significance of translocation t(1;19) in a childhood acute lymphoblastic leukemia in the context of comterporay therapies: a report from the children s cancer group J. Clin. Oncol 1998 16 van der Plas D.C Hahlen K Hagemeijer A Prognostic significance of karyotype at diagnosis in childhood acute lymphoblastic leukemia Leukemia 1992 6 Venegas P Interfase-FISH en un paciente con leukemia mielocítica crónica Rev. Méd. Hosp. Nac. de Niños 2001 a 36 Venegas P Translocación t(4;11) de infantes con leucemia linfocítica aguda Rev. Méd. Hosp. Nac. Niños 2001 b 36 Wu S.Q Weinberg K.I Joo W.J Quinn J.J Franklin J Siegel S.E Gaynon P.S Preponderant mitotic activity of nonleukemic cells plays an imprtant role in failures to detect abnormal clone in childhood acute lymphoblastic leukemia J. Pediatr. Hematol. Oncol 2003 25 Zemanova Z Michalova K Brezinova J Sindelarova L Kurkova S Smisek P Zuna J Trka J Stary J Fluorescent in situ Hybridization (FISH) in the diagnosis of acute childhood lymphatic leukemia (ALL) Cas. Lek. Cesk 2001 140
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300018 Historia e investigación de la leucemia en Costa Rica Jiménez Bonilla Rafael ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 559 569

History of leukemia research in Costa Rica. A review of leukemia worldwide is discussed, focusing on etiology, diagnosis and treatment. The history of research of this type of cancer in Costa Rica is presented through the first hospital diagnosis, the arrival of clinical and laboratory hematologists, the establishment of specialized laboratories, the local hematology teaching programs and the voluntary associations that help patients with leukemia. A brief review of Costa Rican publications in this area and the future of this problem in our country is also shown. Rev. Biol. Trop. 52(3): 559-569. Epub 2004 Dic 15.

Se hace inicialmente una revisión de la historia de la leucemia en el mundo, analizando sus principales causas etiológicas y las primeras formas de diagnóstico y tratamiento. Acontinuación se revisa la historia de la investigación de la leucemia en Costa Rica, puntualizando los diagnósticos iniciales en los hospitales, la llegada de los primeros hematólogos clínicos y de laboratorio, la creación de los laboratorios especializados en Hematología, la aplicación en nuestro país de los modernos tratamientos contra la leucemia y la importancia que para ello tuvieron las relaciones con centros del extranjero. También se presenta la secuencia de la implementación en Costa Rica de las modernas metodologías de ayuda diagnóstica y la importancia que tuvo en el manejo de la leucemia el hecho de que se empezaran a formar en el país nuevos profesionales especializados en la rama de la Hematología, así como la creación de las asociaciones de voluntarios. Por último se presentan algunas de las publicaciones nacionales en leucemia y unos comentarios acerca del futuro del tratamiento y el diagnóstico de los pacientes leucémicos.

 leukemia leukemia history hematology genetics Costa Rica leucemia investigación historia hematología genética Costa Rica Tumores malignos del tejido linfático y de los órganos hematopoyéticos Tumores malignos del tejido linfático y de los órganos hematopoyéticos 1980 Departamento de Estadística, Ministerio de Salud Ardashnikov S.N The genetics of leukemia in man J. Hyg 1937 37 Aur R.A.J Simone J.V Hustu H.O Walters T Borella L Pratt C Pinkel D Central nervous system therapy and combination chemotherapy of childhood lymphocytic leukemia Blood 1971 37 Barth C Altération du sang remarquable par la prédominance des globules blancs ou musqueux ; hypertrophie considérable de la rate Bull. Soc. Méd. 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Trop 2004 52 3 Virchow R Weisses Blut Notiz Geb Natur Heilk 1845 36 Virchow R Virchow R Die Leukäemie Gesammelte Abhandlungen zur Wiessenschaft lichen Medizin Gesammelte Abhandlungen zur Wiessenschaft lichen Medizin 1856 Frankfurt^eMeideinger Zuelzer W Cox D Genetic aspects of leukemia Semin. Hematol 1969 6
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300019 Epilepsia mioclónica progresiva tipo Lafora y los casos diagnosticados en Costa Rica Solís Virginia ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 571 584

Lafora’s progressive myoclonus epilepsy and diagnosed cases in Costa Rica. A review of the main clinical, pathologic and genetic aspects of progressive myoclonus epilepsy Lafora type was undertaken. The diagnosed cases of this disorder in Costa Rica are mentioned. Rev. Biol. Trop. 52(3): 571-584. Epub 2004 Dic 15.

Se presenta una revisión bibliográfica de los principales aspectos clínicos, patológicos y genéticos de la epilepsia mioclónica progresiva tipo Lafora. Se hace mención a los casos de esta enfermedad diagnosticados en Costa Rica.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300020 Mutagénesis ambiental y el uso de biomarcadores para predecir el riesgo de cáncer Cuenca Patricia Ramírez Vanessa ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 585 590

Environmental mutagenesis and use of biomarkers in cancer risk prediction. The field of environmental mutagenesis or toxicology genetics aims to study the genetic damage that leads to mutations produced by physical, chemical and biological agents, to identify these agents and analyze their interactions and ways of action. There are enough experimental and epidemiological evidences implicating mutations in oncogenes, tumor suppressor genes and DNA repair genes as determinants in the onset and progression of the neoplastic process. A valuable tool in public and occupational health is the monitoring of populations exposed to potentially hazardous agents. The objective is to protect the health and quality of life of high risk groups on account of the nature of the agents of exposure. Monitoring of genotoxic effects in exposed populations as well as the analysis of susceptibility polymorphism are visualized as key tools in the realm of future public and occupational health in order to prevent the occurrence of environmental and specially occupational origin of tumors. This paper reviews the main concepts concerning this issue and refers to studies on the subject in Costa Rica. Rev. Biol. Trop. 52(3): 585-590. Epub 2004 Dic 15.

La mutagénesis ambiental o genética toxicológica es una disciplina que tiene como objetivo estudiar el daño genético que conduce a mutaciones, producido por agentes físicos, químicos y biológicos, identificar estos agentes, analizar sus interacciones y mecanismos de acción. Existen suficientes evidencias experimentales y epidemiológicas que demuestran que el proceso cancerígeno se inicia y se favorece por la presencia de mutaciones en los oncogenes, los genes supresores de tumores y los que codifican para los sistemas de reparación del ADN. Una herramienta valiosa en salud pública y ocupacional es el monitoreo de grupos de población expuestos a agentes potencialmente dañinos para el ser humano. Tiene como objetivo preservar la salud y la calidad de vida en aquellos grupos que son de alto riesgo por la naturaleza de las sustancias a que están expuestos. Se vislumbra al monitoreo del efecto genotóxico en poblaciones expuestas, en conjunto con el análisis de polimorfismos de susceptibilidad, como herramientas clave en la salud pública y ocupacional del futuro, para prevenir la ocurrencia de tumores de origen ambiental y especialmente laboral. En este trabajo se revisan los principales conceptos sobre este tema y se hace referencia a los trabajos realizados sobre exposición laboral a potenciales cancerígenos y a la que existe en el monitoreo de poblaciones expuestas en Costa Rica.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300021 Polimorfismos en los genes de desintoxicación CYP1A1, CYP2E1, GSTT1 y GSTM1 en la susceptibilidad al cáncer gástrico González Auxiliadora Ramírez Vanessa Cuenca Patricia Sierra Rafaela ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 591 600

Polymorphisms in detoxification genes CYP1A1, CYP2E1, GSTT1 and GSTM1 in gastric cancer susceptibility. Cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes are involved in activation and detoxification of many potential carcinogens. Genetic polymorphisms in those enzymes have been found to influence the interindividual susceptibility to cancer. Some polymorphisms of those enzymes have been associated specifically with susceptibility to gastric cancer. We conducted a study in a Costa Rican population, where gastric cancer incidence and mortality rates are among the highest in the world. We investigated whether such variations affected the risk of developing gastric cancer. Subjects included 31 with gastric cancer, 58 controls with gastric injures others than cancer and 51 normal controls confirmed by X-rays (double-contrast) or endoscopic diagnostic. DNA from peripheral white blood cell was obtained from all subjects. Deletion of GSTT1 and GSTM1 was assessed by multiplex PCR and genotyping of CYP2E1 was performed using a PCR-based restriction fragment length polymorphism assay with the restriction enzyme PstI and the gene CYP1A1 using the restriction enzyme MspI. The prevalence of CYP1A1 MspI polymorphism, GSTT1 and GSTM1 null genotype was similar in the three groups of individuals (p=0.73, p=0.88 y p= 0.89 respectively). Our findings suggest that the polymorphism CYP2E1 PstI could be associated with a reduced risk of having gastric cancer (OR=0.09, IC95% :0.01 - 0.83). Rev. Biol. Trop. 52(3): 591-600. Epub 2004 Dic 15.

Las enzimas de las familias P450 y Glutation S-transferasa están relacionadas en la activación y desintoxicación de sustancias que podrían actuar como cancerígenas. Polimorfismos genéticos en estas enzimas han sido asociados con un incremento en el riesgo de desarrollar cáncer específicamente con un mayor riesgo de desarrollar cáncer gástrico. En esta investigación se estudió un grupo de costarricenses con alto riesgo de cáncer gástrico. Se estudiaron 31 individuos con cáncer gástrico, 51 controles normales confirmados por rayos X (serie gastroduenal de doble contraste) o por endoscopía y 58 individuos con otras lesiones gástricas. Se estudiaron los polimorfismos de desintoxicación química CYP1A1 MspI y CYP2E1 PstI, los cuales presentan una mayor expresión enzimática y los polimorfismos de los genes GSTT1 y GSTM1 que carecen de un producto proteínico funcional y su relación con lesiones gástricas leves y cáncer gástrico. El ADN de los pacientes fue aislado a partir de leucocitos de sangre periférica. Los polimorfismos de los genes GSTT1 y GSTM1 fueron evaluados mediante un PCR múltiple y para los polimorfismos CYP2E1 PstI y CYP1A1 MspI se realizó un PCR seguido por la digestión con las enzimas de restricción PstI y MspI respectivamente. La prevalencia del polimorfismo CYP1A1 MspI, y de los polimorfismos GSTT1 y GSTM1 sin actividad enzimática, fue similar en los tres grupos estudiados (p=0.73, p=0.88 y p= 0.89 respectivamente). Los resultados sugieren que el alelo CYP2E1 Pst1 podría actuar como factor protector contra el cáncer gástrico (OR=0.09, IC al 95%: 0.01-0.83).

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300022 Genotoxicidad de tres plaguicidas utilizados en la actividad bananera de Costa Rica Vindas Rebeca Ortiz Fernando Ramírez Vanessa Cuenca Patricia ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 601 609

Genotoxicity of three pesticides used in Costa Rican banana plantations. The in vitro genotoxicity of imazalil and thiabendazole fungicides and the insecticide chlorpyrifos, compounds used in Costa Rican banana plantations, was evaluated with the single-cell gel electrophoresis technique (comet assay). The comet assay is a simple, rapid and low cost technique for quantification of DNA damage. This assay detects DNA single- strand breaks and alkalilabile sites in individual cells. The effects were analyzed by using human lymphocytes exposed to doses of 0, 25, 50, 75 and 100 µg/ml of each pesticide for 30 min at 37°C. The cells were embedded in agarose, lysed, subjected to alkaline electrophoresis (pH> 13) for 20 min at 25V, neutralized and dehydrated to be stained with a fluorescent dye and later comets visualization with the epifluorescence microscope. Chlorpyrifos and imazalil induced significant DNA damage in a dose-dependent manner. Chlorpyrifos was the major inductor of DNA breaks. These results indicate that both are genotoxic compounds in vitro. Thiabendazole fungicide did not induced DNA damage using the comet assay for all concentrations tested. Rev. Biol. Trop. 52(3): 601-609. Epub 2004 Dic 15.

Se evaluó la genotoxicidad in vitro de los fungicidas imazalil y tiabendazol y del insecticida clorpirifos, formulaciones empleadas en las bananeras costarricenses, utilizando la técnica de electroforesis de células únicas (ensayo cometa). El ensayo cometa es una técnica simple, rápida y de bajo costo para la cuantificación de daños en el ADN, en términos de rupturas y sitios álcalilábiles, en la hebra simple del ADN de células individuales. Se expusieron linfocitos humanos a concentraciones de 0, 25, 50, 75 y 100 µg/ml de los plaguicidas, por 30 min a 37°C. Las células fueron embebidas en agarosa, se provocó la lisis de sus membranas citoplasmáticas y se sometieron a electroforesis alcalina durante 20 min a 25V. Por último, las preparaciones se neutralizaron y se deshidrataron, para el posterior teñido de las láminas con el fluorocromo y la visualización de los cometas en el microscopio de epifluorescencia. El clorpirifos y el imazalil inducen daños significativos en la hebra sencilla del ADN en forma dependiente de la concentración, siendo el clorpirifos el mayor inductor de rupturas en el material genético. Estos resultados indican que ambos se comportan como compuestos genotóxicos in vitro. El fungicida tiabendazol mostró resultados negativos en las concentraciones empleadas.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300023 Micronúcleos y otras anormalidades nucleares en el epitelio oral de mujeres expuestas ocupacionalmente a plaguicidas Castro Rocío Ramírez Vanessa Cuenca Patricia ,Universidad de Costa Rica ,Universidad de Costa Rica ,Universidad de Costa Rica 09 2004 2004 52 611 621

Micronuclei and other nuclear abnormalities in the oral epithelium of female workers exposed to pesticides. In order to study if banana fields labour exposure to pesticides produces some kind of DNA damage, we determine the presence of micronuclei in epithelial oral cells in working women in Guapiles and Siquirres, Costa Rica, as an effect biomarker. We also analyzed other abnormalities in the nucleus of those cells such as broken-egg, karyolysis or kariorrhexis, to see if there was some kind of genotoxicity or citotoxicity. The women group exposed to pesticides worked in packing bananas plant from different independent farms. The control group of women had never done any farming tasks; they did not live in the banana fields, neither their husband. We got information about the life style, medical and familial history of the participants through an interview. We did not found any significant increment in the frequency of micronuclei form the exposed group compared with the controls. The other nuclei abnormalities showed signs of citotoxicity or genotoxicity in the controls, associated with the intake of coffee and dental x-rays. These results do not rule out at that pesticides used in packing bananas are agents capable of producing damage to the DNA, but it seems that micronuclei from the oral epithelium is not the most adequate marker to measure it. Rev. Biol. Trop. 52(3): 611-621. Epub 2004 Dic 15.

Para determinar si la exposición laboral a plaguicidas produce daño al material genético se utilizó como biomarcador de efecto la presencia de micronúcleos en células del epitelio oral de trabajadoras de Guápiles y Siquirres, Costa Rica. También se analizaron otras anormalidades nucleares que pueden ser indicio de genotoxicidad o de citotoxicidad. El grupo de mujeres expuestas a plaguicidastrabajaban en plantas empacadoras de diferentes fincas bananeras independientes. El grupo de mujeres no expuestas nunca habían trabajado en labores agrícolas, no vivían dentro de una finca bananera, así como tampoco sus esposos o compañeros. Se obtuvo información acerca del estilo de vida, historia médica y familiar de las participantes mediante una entrevista. No se encontró un aumento significativo en la frecuencia de micronúcleos en el grupo de expuestas con respecto a las no expuestas. Las otras anormalidades nucleares mostraron indicios de citotoxicidad y genotoxicidad en el grupo de no expuestas, asociados a ingesta de café y a radiografías dentales. Estos resultados no descartan a los plaguicidas como agentes capaces de causar daño genético, sino que más bien los micronúcleos de la mucosa oral no parecen ser el biomarcador más adecuado para medirlo.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300024 Aberraciones cromosómicas en trabajadoras expuestas a plaguicidas Cuenca Patricia Ramírez Vanessa ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 623 628

Chromosomic aberrations in female workers exposed to pesticides. The purpose of this work was to determine if the occupational exposure to those pesticides used at banana plantations’ packaging plants produces genetic damage to somatic cells of female workers. Chromosomal aberrations were scored in lymphocytes of 20 women, 10 female exposed workers and 10 female controls. Workers were recruited from independent farms from two locations in Costa Rica, during January through June in 1996 and 1997. These females had a minimum of three months of work, had never received chemotherapy or radiotherapy and did some of these labors: sealing, spraying or weighting of bananas. Control unexposed females lived in the same area, were of similar age and neither them nor their husbands/mates had ever worked in pesticide related labors. For each female, 100 mitotic figures were scored. The kind of aberrations detected were acentric fragments, dicentric chromosomes, rings, gaps and breaks. Among workers, 16% of cells (n=1000) had one or more abnormalities, whereas control unexposed females had 6% of cells (n=1000) with comparable anomalies (p<0.05). In conclusion, the pesticide exposure is a risk factor for chromosome aberrations in female somatic cells. Rev. Biol. Trop. 52(3): 623-628. Epub 2004 Dic 15.

Con el objetivo de conocer si la exposición ocupacional a los plaguicidas utilizados en las plantas empacadoras de banano provoca daño genético en las células somáticas de las trabajadoras, se estudió la frecuencia de aberraciones cromosómicas en linfocitos de un grupo de diez trabajadoras expuestas y diez mujeres no expuestas. Las trabajadoras se captaron en fincas independientes de los cantones de Guácimo y Pococí, Costa Rica, entre enero y junio de los años 1996 y 1997. El grupo de expuestas tenían un mínimo de tres meses de trabajo, no habían recibido quimioterapia o radioterapia, y realizaban alguna de las siguientes labores: sellar, atomizar y/o pesar la fruta. El grupo de no expuestas estuvo formado por mujeres residentes de la misma zona, con edades similares; tanto ellas como sus esposos o compañeros no trabajaban en labores relacionadas con plaguicidas. Se analizaron 100 figuras mitóticas por persona y se registraron las aberraciones siguientes: fragmentos acéntricos, cromosomas dicéntricos, anillos, lagunas y fracturas cromosómicas. El 16% de las células (n = 1000) pertenecientes a las trabajadoras tenían una o más anormalidades contra el 6% (n = 1000) en el grupo de mujeres no expuestas (p <= 0.05).

 pesticides chromosomal aberrations Costa Rica banana parking pesticidas aberraciones cromosómicas Costa Rica empacado de banano Occupational cancer in developing countries Occupational cancer in developing countries 1994 129 Lyon Ashby J Angbar W Au W Massoud A Gentile J Genetic Toxicology in Developing Countries: Comments and recommendations Environ. Health Perspect 1993 101 Au W Monitoring human populations for effects of radiation and chemical exposures using cytogenetics techniques Ocupational Med 1991 6 Au W Walker D.M Ward J.B Whorton E Legator M Singh V Factors contributing to chromosome damage in lymphocytes of cigarette smokers Mut. Res 1991 260 Au W Sram R Second International Conference on Environmental Mutagens in Human Populations Environ Health Perspect 1996 104 ^sSuppl 3 Au W Sierra-Torres C.H Cajas-Salazar N Shipp B.K Legator M. S Cytogenetic effects from exposure to mixed pesticides and the infkuence from genetic susceptibility Environ. Health Perspect 1999 107 Bonassi S Au W.W Biomarkers in molecular epidemiology studies for health risk prediction Mutat. Res 2002 511 Carrano A.V Natarajan A.T Consideration for population monitoring using cytogenetic techniques. International Commision for Protection against environmental mutagens and carcinogens. Publication No 14 Mut. Res 1988 204 Castro R Ramírez V Cuenca P Análisis de micronúcleos y otras anormalidades nucleares en el epitelio oral de mujeres expuestas ocupacionalmente a plaguicidas Rev. Biol. Trop 2004 52 Cuenca P Ramírez V Mutagénesis ambiental y el uso de biomarcadores para predecir y prevenir el riesgo de cáncer 2004 52 Dulout F.N Pastori M.C Olivero A.O González Cid M Loría D Matos E Sobel N de Buján E.C Albiano N Sisterchromatid exchanges and chromosomal aberrations in a population exposed to pesticides Mut. Res 1985 143 Fear N.T Childhood cancer and paternal employment in agriculture: the role of pesticides Br. J. Cancer 1998 77 García J Plaguicidas: Problemática y opciones de solución, con énfasis en Costa Rica. Foro Latinoamericano Acta Académica 2003 33 Hagmar L Brogger A Hansteen I.L Heim S Högstedt B Knudsen L Lambert B Linnainmaa K Mitelman F Nordenson I Reuterwall Ch Salomaa S Skerfving S Sorsa M Cancer risk in human predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic Study Group on the Health Risk of Chromosome Damage Cancer Res 1994 54 Hagmar L Bonassi S Stromberg U Brogger A Knudsen L Norppa H Reuterwall C Chromosomal aberrations in lymphocytes predict human canmcer: A report from the European Study Group on Cytogenetics Biomarkers and Health (ESCH) Cancer Res 1998 58 Hernández O Bolaños R.L SPSS/PC + básico SPSS/PC + básico 1993 San José Editorial de la Universidad de Costa Rica Nordenson I Beckman L Liden S Stjernberg N Chromosomal Aberration and Cancer Risk Hum. Hered 1984 34 Pearce N Matos E Vainio H Boffetta P Kogevinas M Occupation cancer in developing countries Occupation cancer in developing countries 1994 Lyon IARC Scientific Publication Preston R.J McGregor D.B Rice J.M Venitt S Chromosomal changes The use of short- and medium-term test for carcinogens and data on genetic effects in carcinogenic Hazard evaluation The use of short- and medium-term test for carcinogens and data on genetic effects in carcinogenic Hazard evaluation 1999 146 Lyon Ramírez A.L Ramírez C.M Esterilidad masculina causada por la exposición laboral al nematicida 1,2-Dibromo- 3-Cloropropano Act. Méd. Cost 1980 23 Ramírez V Cuenca P Micronuclei frecuency in lymphocytes of individuals occupationally exposed to pesticides Rev. Biol. Trop 2001 49 Ramírez V Cuenca P Daño del ADN en trabajadoras bananeras expuestas a plaguicidas en Limón, Costa Rica Rev. Biol. Trop 2002 50 Savitz D.A Sonnenfeld N.L Olshan A.F Review of Epidemiologic Studies of Paternal Occupational Exposure and Spontaneous Abortion Am. J. Industrial Med 1994 25 Sorsa M Wibourn J Vainio H Vainio H Magee P.N McGregor D.B Mc Michael A.J Human Cytogenetic damage as a predict of cancer risk Mechanism of carcinogénesis in risk identification Mechanism of carcinogénesis in risk identification 1992 Lyon IARC Scientific Publications Vaquerano B Establecimiento de controles normativos (restricciones y prohibiciones) a los plaguicidas sintéticos. Memoria del foro sectorial: "El uso de plaguicidas y su relación con el desarrollo en Costa Rica". Proyecto PLAGSALUD, OPS / OMS, Rel-UITA, Foro Emaús Establecimiento de controles normativos (restricciones y prohibiciones) a los plaguicidas sintéticos. Memoria del foro sectorial: "El uso de plaguicidas y su relación con el desarrollo en Costa Rica". Proyecto PLAGSALUD, OPS / OMS, Rel-UITA, Foro Emaús 2001 San José Wesseling C Ahlbom A Antich D Rodriguez A.C Castro R Cancer in banana plantation workers in Costa Rica Int. J. Epidemiol 1996 24
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300025 Is the Central Valley of Costa Rica a genetic isolate? Morera Bernal Barrantes Ramiro ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica 09 2004 2004 52 629 644

In the last decade, the Costa Rican Central Valley population (CRCV), has received considerable scientific attention, attributed in part to a particularly interesting population structure. Two different and contradictory explanations have emerged: (1) An European-Amerindian-African admixed population, with some regional genetic heterocigosity and moderate degrees of consanguinity, similar to other Latin-American populations. (2) A genetic isolate, with a recent founder effect of European origin, genetically homogeneous, with a high inter-marriage rate, and with a high degree of consanguinity. Extensive civil and religious documentation, since the settlement of the current population, allows wide genealogy and isonymy studies useful in the analysis of both hypotheses. This paper reviews temporal and spatial aspects of endogamy and consanguinity in the CRCV as a key to understand population history. The average inbreeding coefficients ?(alpha ) between 1860 and 1969 show a general decrease within time. The consanguinity in the CRCV population is not homogeneous, and it is related to a variable geographic pattern. Results indicate that the endogamy frequencies are high but in general it was not correlated with alpha ?values. The general tendency shows a consanguinity decrease in time, and from rural to urban communities, repeating the tendencies observed in other countries with the same degree of development, and follows the general Western World tendency. Few human areas or communities in the world can be considered true genetic isolates. As shown, during last century, the CRCV population has had consanguinity values that definitively do not match those of true genetic isolates. A clear knowledge of the Costa Rican population genetic structure is needed to explain the origin of genetic diseases and its implications to the health system. Rev. Biol. Trop. 52(3): 629-644. Epub 2004 Dic 15.

En la última década, la población del Valle Central de Costa Rica (CRCV) ha recibido una considerable atención científica, lo que puede ser atribuido en parte a su estructura poblacional, la cual es singularmente interesante. Dos explicaciones diferentes y contradictorias han surgido: por un lado, (1) una población mezclada europea-amerindia- africana, con alguna heterogenidad genética regional y moderados grados de consanguinidad, similar a otras poblaciones de América Latina. Por otro lado, (2) un aislado genético, con un efecto fundador reciente, que es particularmente de origen europeo, genéticamente homogenea, con alta endogamia y con un alto grado de consanguinidad. La extensa documentación civil y religiosa, desde el establecimiento de la población multiétnica actual, permite hacer amplios estudios genealógicos y de isonimia útiles para el análisis de ambas hipótesis. Este trabajo tiene por objetivo revisar los aspectos temporales y espaciales de la endogamia y la consanguinidad en el Valle Central como una clave para la comprensión de la historia poblacional. Los coheficientes medios de endocruzamiento &#61480;a) entre 1860 y 1969 muestran una reducción en el tiempo. La consanguinidad en el Valle Central no es homogenea, ya que un patrón de variación geográfico fue observado. Los resultados indican que la frecuencia de endogamia es alta pero en general no está correlacionada con los valores de a. La tendencia general muestra que la consanguinidad y la endogamia decrecen en el tiempo, y desde las comunidades rurales a las urbanas, repitiendo las tendencias observadas en otros países con el mismo grado de desarrollo, y siguen la tendencia general de la sociedad occidental. Pocas áreas y comunidades humanas en el mundo pueden ser consideradas aislados genéticos. Como se muestra, durante el último siglo, la población del Valle Central ha tenido valores de consanguididad que definitivamente no concuerdan con los verdaderos aislados genéticos. Un preciso conocimiento de la estructura poblacional en términos de consanguinidad es necesario debido a sus implicaciones para el sistema de salud costarricense.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300026 The STR polymorphism (AAAAT)n within the intron 1 of the tumor protein 53 (TP53) locus in 17 populations of different ethnic groups of Africa, America, Asia and Europe Azofeifa Jorge Hahn Meinhard Ruiz Edward Hummerich Lars Morales Ana I Jiménez Gerardo Barrantes Ramiro ,Universidad de Costa Rica ,Institut für Biochemie Heidelberg Germany ,Organismo de Investigaciones Judiciales Costa Rica ,Universidad de Costa Rica 09 2004 2004 52 645 657

The STR (AAAAT)n within intron 1 of the TP53 locus was screened in 17 populations from 3 main ethnic groups: Europeans, Asiatics, and Africans, and from the hybrid population of Costa Rica (1968 samples). Three alleles, 126/7 (bp/copies of the repeat), 131/8 and 136/9 were the most prevalent in all populations. Other alleles rarely reached frequencies of 10% or higher. Observed heterozygosities ranged between 0.351 and 0.829. Patterns of diversity fit well with both the geographic origin of the samples and the history of the populations screened. A statistical test suggests that single-step mutational events have been the main mechanism producing new alleles at this locus. Fixation indexes (R ST ) for this marker showed an effect of population subdivision on divergence only within the Asiatic group; they were insensitive at the level of major ethnic groups as well as within Africans and within Europeans. Rev. Biol. Trop. 52(3): 645-657. Epub 2004 Dic 15.

Se estudió el polimorfismo del microsatélite (AAAAT)n del intrón 1 del gene TP53 en 17 poblaciones de 3 grupos étnicos: europeos, asiáticos, y africanos subsaharianos, así como de la población híbrida de Costa Rica (en total 1968 muestras). Tres alelos, 126/7 (pares de bases/ copias de la repetición), 131/8 y 136/9 fueron los más frecuentes en todas las poblaciones, aunque se observaron otros alelos usualmente a frecuencias menores al 10%. Las heterocigosis observadas variaron de 0.351 a 0.829. La distribución de la diversidad parece concordar con el origen geográfico de las muestras y con la historia de las poblaciones estudiadas. Una prueba estadística indica que el evento mutacional que más alelos nuevos produce en este marcador es el de un solo paso (expansión o contracción de una sola copia de la repetición). El índice de fijación R ST mostró los efectos de la subdivision de poblaciones sólo dentro del grupo de los asiáticos y mostró falta de sensibilidad cuando los grupos comparados eran de niveles superiores de clasificación (europeos, asiáticos, y africanos) o cuando la comparación se hizo entre los grupos más antiguos (africanos y europeos).

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Genet 1999 78 Fix A.G Migration and Colonization in Human Microevolution Migration and Colonization in Human Microevolution 1999 Cambridge Cambridge University Futreal P.A Barret J.C Wiseman R.W An Alu polymorphism intragenic to the TP53 gene Nucl. Acids Res 1991 19 Gaspar P.A Hutz M.H Salzano F.M Weimer T.A TP53 polymorphisms and haplotypes in South Amerindians and neo-Brazilians Ann. Hum. Biol 2001 28 Gaspar P.A Hutz M.H Salzano F.M Hill K Hurtado A.M Petz-Erler ML Tsuneto L.T Weimer T.A Polymorphisms of CYP1A1, CYP2E1, GSTM1, GSTT1, and TP53 genes in Amerindians Am. J. Phys. Anthrop 2002 119 Griffiths R.C Tavare S Simulating probability distributions Theor. Pop. Biol 1994 46 Guo S Thompson E Performing the exact test of the Hardy-Weinberg proportion for multiple alleles Biometrics 1992 48 Gusmão L Prata M. J Amorim A Silva F Bessa I Characterization of four short tandem repeat loci (THO1, VWA31/A, CD4, and TP53) in Northern Portugal Hum. 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A software for population genetic data analysis. Genetic and Biometry Laboratory, Department of Anthropology Arlequin version 1.1. A software for population genetic data analysis. Genetic and Biometry Laboratory, Department of Anthropology 1997 University of Geneva Själander A Birgander R Kivelä A Beckman G p53 Polymorphisms and haplotypes in different ethnic groups Hum. Hered 1995 45 Själander A Birgander R Saha N Beckman L Beckman G p53 polymorphisms and haplotypes show distinct differences between major ethnic groups Hum. Hered 1996 46 Slatkin M A measure of population subdivision based on microsatellite allele frequencies Genetics 1995 139 Wehrhan C.F The evolution of selectively similar electrophoretically detectable alleles in finite natural populations Genetics 1975 80 Zerylnick C Torroni A Sherman S.L Warren S.T Normal variation at the myotonic dystrophy locus in global human populations Am. J. Hum. 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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300027 Polimorfismo del gen de la banda 3 eritrocítica en grupos étnicos de Costa Rica Chaves-Villalobos M Jiménez-Arce G Sandí-Díaz M ,Universidad de Costa Rica ,Hospital Nacional de Niños Dr. Carlos Sáenz Herrera 09 2004 2004 52 659 663

Polymorphism of the erythrocyte band 3 gene (EPB3) in ethnic groups of Costa Rica. Band 3 (AE1) is one of the most abundant proteins in the membrane of the human erythrocyte. This protein works as an anionic CI - and HCO3- exchanger and it also functions as an anchor for several proteins of the erythrocyte's cytoesqueleton. Several mutations have been described and many polymorphic variants have been associated to hereditary spherocytosis. The identification of a genetic marker at position 5' of the AE1 gene could be associated to several molecular defects of the erythrocyte. This genetic marker is a restriction fragment length polymorphism (RFLP) produced by restriction enzime Pst I. For this polymorphism a total of 216 individuals belonging to seven different populations were analyzed: one from the Central Valley, two African descendants (Limón and Guanacaste) and four Amerindians (Bribri, Cabecar, Maleku and Guaymi). The most frequent allele in the Amerindian population was no 1. No significant differences were found with respect to the Hardy-Weinberg equilibrium in six of the populations, although the Guaymi group does present significative differences. Rev. Biol. Trop. 52(3): 659-663. Epub 2004 Dic 15.

Banda 3 (AE1) es una de las proteínas más abundantes de la membrana del eritrocito humano. Ésta funciona como un intercambiador aniónico cloruro / bicarbonato y es el punto de anclaje de varias proteínas del citoesqueleto del eritrocito. Se han descrito varias mutaciones y muchas variantes polimórficas se han asociado a esferocitosis hereditaria. La identificación de un marcador genético en el extremo 5’ del gene AE1 podría asociarse a varios defectos moleculares del eritrocito. Este marcador genético es un fragmento de restricción de longitud polimórfica "RFLP" producido por la endonucleasa de restricción Pst I. Se analizaron para este polimorfismo un total de 216 individuos de siete poblaciones: una hispanomestiza (Valle Central), dos afrodescendientes (Limón y Guanacaste) y cuatro amerindias (bribri, cabecar, maleku y guaymí). El alelo más frecuente en la población hispanomestiza fue el 2, mientras en los grupos afrodescendientes y amerindios se encontró el 1. No se observaron diferencias significativas con respecto al equilibrio de Hardy-Weinberg en seis de las poblaciones, sin embargo, el grupo Guaymí si presenta diferencias significativas con respecto al equilibrio de Hardy-Weinberg.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300028 A phylogeny of howler monkeys (Cebidae: Alouatta) based on mitochondrial, chromosomal and morphological data Villalobos Federico Valerio Alejandro A Retana Axel P ,Instituto Centroamericano para la Investigación en Biología y Conservación (ICIBC) San Pedro de Montes de Oca San José Costa Rica ,Instituto Centroamericano para la Investigación en Biología y Conservación (ICIBC) 09 2004 2004 52 665 677

The current taxonomic status of the species and subspecies belonging to the genus Alouatta is addressed by combined phylogenetic analysis using morphological, kariotipyc and molecular data (mitochondrial genes cytocrome oxidase II and cytochrome B). Our result demonstrated that Alouatta palliata is the most basal taxon for the genus in concordance with previous studies, as well as showing the validity of the taxon Alouatta sara as a species. Also our analysis shows that the sex chromosome has evolved from a XY/XX system to a X1X2Y1Y2/X1X1X2X2 system within the genus, as well as an increase in the size and complexity of the hioideal bone. Rev. Biol. Trop. 52(3): 665-677. Epub 2004 Dic 15.

El estado taxonómico actual de las especies y subespecies del genero Alouatta (Lacépède, 1799) fue estudiado empleando un análisis filogenético combinado de datos morfológicos, cariotipicos y moleculares (genes mitocontridales del Citocromo Oxidasa II y el Citocromo B). Nuestros resultados demuestran que Alouatta palliata (Gray 1949) es la especie mas basal del genero en concordancia con propuestas previas para el grupo, también muestran la valides de Alouatta sara (Elliot 1910) como una especie. Nuestros análisis también muestra que los cromosomas sexuales evolucionaron de un sistema XY/XX a un sistema X1X2Y1Y2/X1X1X2X2 dentro del genero así como también un incremento en el tamaño y complejidad del hueso hioideo.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300029 Distribution, ecology, life history, genetic variation, and risk of extinction of nonhuman primates from Costa Rica Zaldívar María E Rocha Oscar Glander Kenneth E Aguilar Gabriel Huertas Ana S Sánchez Ronald Wong Grace ,Universidad de Costa Rica San José Costa Rica ,Kent State University Cunningham Hall OH USA ,Duke University Durham NC U.S.A ,Universidad de Costa Rica San Ramón de Alajuela Costa Rica ,Universidad Nacional de Costa Rica Heredia Costa Rica 09 2004 2004 52 679 693

We examined the association between geographic distribution, ecological traits, life history, genetic diversity, and risk of extinction in nonhuman primate species from Costa Rica. All of the current nonhuman primate species from Costa Rica are included in the study; spider monkeys (Ateles geoffroyi), howling monkeys (Alouatta palliata), capuchins (Cebus capucinus), and squirrel monkeys (Saimiri oerstedii). Geographic distribution was characterized accessing existing databases. Data on ecology and life history traits were obtained through a literature review. Genetic diversity was characterized using isozyme electrophoresis. Risk of extinction was assessed from the literature. We found that species differed in all these traits. Using these data, we conducted a Pearson correlation between risk of extinction and ecological and life history traits, and genetic variation, for widely distributed species. We found a negative association between risk of extinction and population birth and growth rates; indicating that slower reproducing species had a greater risk of extinction. We found a positive association between genetic variation and risk of extinction; i.e., species showing higher genetic variation had a greater risk of extinction. The relevance of these traits for conservation efforts is discussed. Rev. Biol. Trop. 52(3): 679-693. Epub 2004 Dic 15.

Se estudió la asociación entre la distribución geográfica, algunos rasgos ecológicos, las historias de vida, la diversidad genética y el riesgo de extinción, en primates no humanos de Costa Rica. Se incluyen todas las especies de primates no humanos del país: los monos araña (Ateles geoffroyi), congo (Alouatta palliata), cara blanca (Cebus capucinus), y tití (Saimiri oerstedii). La distribución geográfica se caracterizó utilizando principalmente bases de datos existentes. Se obtuvo información acerca de sus características ecológicas y de historias de vida mediante una revisión bibliográfica. Se estudió su diversidad genética utilizando electroforesis de isoenzimas. El riesgo de extinción se evaluó usando información bibliográfica. Se encontró que las cuatro especies presentaban variación en todos estos rasgos. Con estos datos, se realizó una correlación de Pearson entre el riesgo de extinción y las variables indicadoras de la distribución geográfica, los rasgos ecológicos, las historias de vida y la diversidad genética, para aquellas especies con una amplia distribución geográfica. Se encontró una asociación entre el riesgo de extinción y la natalidad y la tasa de crecimiento poblacional; las especies con menor natalidad y menor tasa de crecimiento poblacional tenían mayor riesgo de extinción. Se encontró una asociación positiva entre la diversidad genética y el riesgo de extinción; las especies con mayor diversidad genética tenían mayor riesgo de extinción. Se discute la importancia de estos rasgos para la conservación de estas especies.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300030 La implementación forense de la tecnología del ADN en Costa Rica: Un análisis retrospectivo Morales C Ana Isabel Morera Bernal Jiménez-Arce Gerardo ,Poder Judicial Heredia Costa Rica ,Universidad de Costa Rica ,Universidad de Costa Rica 09 2004 2004 52 695 712

Forensic implementation of DNA technology in Costa Rica: a retrospective analysis. La reciente utilización de la tecnología del ADN para la identificación individual a traído consigo una revolución en las ciencias forenses, que ha alcanzado también a la America Latina. El análisis histórico muestra que en Costa Rica se han logrado importantes avances y en la actualidad se encuentra consolidado el trabajo con los STRs, y se están en proceso de implementación los marcadores de ADNmt y del cromosoma Y. Sin embargo, la incorporación de las innovaciones de la genética forense se ha venido realizando, cíclicamente, de 5 a 10 años tarde respecto a los paises desarrollados en este campo. Se espera un cambio de actitud en el futuro, al estar disponibles nuevas generaciones de marcadores de ADN, que permitan explotar a corto plazo todo el potencial de esta útil herramienta al servicio de la justicia. Rev. Biol. Trop. 52(3): 695-712. Epub 2004 Dic 15.

La reciente utilización de la tecnología del ADN para la identificación individual a traído consigo una revolución en las ciencias forenses, que ha alcanzado también a la America Latina. El análisis histórico muestra que en Costa Rica se han logrado importantes avances y en la actualidad se encuentra consolidado el trabajo con los STRs, y se están en proceso de implementación los marcadores de ADNmt y del cromosoma Y. Sin embargo, la incorporación de las innovaciones de la genética forense se ha venido realizando, en forma cíclica, de 5 a 10 años tarde respecto a los paises desarrollados en este campo. Se espera un cambio de actitud en el futuro, al estar disponible una nueva generación de marcadores de ADN, que permita así utilizar en forma pronta, todo el potencial de esta útil técnología.

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Legal Med 1996 109 Olaisen B Bar W Brinkmann B Budowle B Carracedo A Gill P Lincoln P Mayr W.R Rand S DNA recommendations 1997 of the International Society for Forensic Genetics Vox Sang 1998 74 Oliveira R.N Nunes F.D Anzai E.K Daruge E Mesquita R.A Ozaki A.N Hirata R.D Hirata MH Population studies of the Y-chromosome of loci DYS390, DYS391 and DYS393 in Brazilian subjects and its use in human identification J. Forensic Odontostomatol 2002 20 1 Padula R.A Gangitano D.A Juvenal G.J Budowle B Allele frequency in the population of Buenos Aires (Argentina) using AmpliType PM + DQA1 J. Forensic Sci 1999 44 Pagano S Alvarez J.C Entrala C Lorente J.A Lorente M Budowle B Villanueva E Uruguayan population data for eight STR loci (using the PowerPlex 1.2 kit) J. Forensic Sci 2001 46 Pawlowski R Paszkowska R Hauser R Brinkmann B Population studies of three AMPFLPs systems in a north Polish population Int. J. Legal Med 1996 109 Pena S Chakraborty R Paternity testing in the DNA era Trends Genet 1994 10 Pepinski W Skawronska M Janica J Human population genetics of the VNTR locus D1S80 in the north-eastern Poland Rocz. Akad. Med. Bialymst 1996 a 41 Pepinski W Skawronska M Janica J DNA locus HLA-DQ alpha polymorphism in human population of the north-eastern Poland Rocz. Akad. Med. Bialymst 1996 b 41 Perez L Hau J Garcia O HLA-DQA1 and polymarker allele frequencies in Peru J. Forensic Sci 2003 48 Perez-Lezaun A Calafell F Clarimon J Bosch E Mateu E Gusmao L Amorim A Benchemsi N Bertranpetit J Allele frequencies of 13 short tandem repeats in population samples from the Iberian Peninsula and northern Africa Int. J. Legal Med 2000 113 Pestoni C Garcia-Ribero A Bellas S Lareu M.V Rodriguez-Calvo M.S Barros F Muñoz I Carracedo A Allele frequency distribution of 15 PCR-based DNA polymorphisms in the population of Galicia (NW Spain) Advance. Forensic Haemogenet 1996 6 Peterson B.L Su B Chakraborty R Budowle B Gaensslen R.E World population data for the HLA-DQA1, PM and D1S80 loci with least and most common profile frequencies for combinations of loci estimated following NRC II guidelines J. Forensic Sci 2000 45 Pinheiro M.F Pontes ML The distribution of HLA DQA1 alleles in the population of the North of Portugal Advance. Forensic Haemogenet 1994 5 Pinheiro M.F Pontes M.L Huguet E Gene M da Costa J.P Moreno P Study of three AMPFLPs (D1S80, 3’ApoB and YNZ22) in the population of the north of Portugal Forensic Sci. Int 1996 79 Pontes M.L Pinheiro MF Study of D1S80 locus polymorphism in the North of Portugal Advance. Forensic Haemogenet 1994 5 Prieto V Andres M.I Flores I.C Sanz P Southern Spain population frequencies of the loci LDLR, GYPA, HBGG, D7S8 and GC. Acomparison between Andalusian and Canary Islands frequencies Advance. Forensic Haemogenet 1996 6 Pushkarev V.P Novikov P.I Population study of D1S80 locus in Caucasians living in the Ural region of Russia by capillary electrophoresis Sud. Med. Ekspert 2001 44 2 Pushkarev V.P Novikov P.I Population study of HLA DQA1, LDLR, GYPA, HBGG, D7S8, and GC loci in Caucasians living in the Ural region of Russia Sud. Med. Ekspert 2002 45 2 Quevedo A Genes en tela de juicio Genes en tela de juicio 1997 Madrid McGraw-Hill Rangel-Villalobos H Jaloma-Cruz A.R Cerda-Aguilar L Rios-Angulo C.D Mendoza-Carrera F Patino-Garcia B Sandoval-Ramirez L Figuera-Villanueva L.E The genetic DNA trace in men: chromosome Y haplotypes in a Mexican population, analyzing 5 STRs Rev. Invest. Clin 2001 53 Rangel-Villalobos H Rivas F Torres-Rodriguez M Jaloma-Cruz A.R Gallegos-Arreola M.P Lopez-Satow J Cantu J.M Figuera L.E Allele frequency distributions of six Amp-FLPS (D1S80, APO-B, VWA, TH01, CSF1PO and HPRTB) in a Mexican population Forensic Sci. Int 1999 105 Robinson S.L Gutowski S.J van Oorschot R.A Fripp Y Mitchell J Genetic diversity among selected ethnic subpopulations of Australia: evidence from three highly polymorphic DNA loci Hum. Biol 1996 68 Rodriguez-Calvo M.S Bellas S Souto L Vide C Valverde E Carracedo A Population data on the loci LDLR, GYPA, HBGG, D7S8 and GC in three Southwest European populations J. Forensic Sci 1996 41 Rodriguez-Calvo M.S Bellas S Souto L Vide C Valverde E Carracedo A Population data on the loci LDLR, GYPA, HBGG, D7S8 and GC in three Southwest European populations J. Forensic Sci 1996 41 Rojas Incera E Análisis de marcadores polimórficos de ADN para pruebas de identidad Análisis de marcadores polimórficos de ADN para pruebas de identidad 1995 Rojas E Lobo J León P Análisis de doce marcadores polimórficos en el ADN de una muestra poblacional del Valle Central costarricense Acta Méd. Cost 1999 41 3 Rose G De Luca M Falcone E Spadafora P Carrieri G De Benedictis G Allele frequency distributions at seven DNA hypervariable loci in a population sample from Calabria (southern Italy) Gene Geogr 1996 10 2 Sanchez-Molina I Calvet R Allelic frequencies for the HLA-DQA1, D1S80, HUMTH01, HUMT-POX, HUMCSF1PO and HUMVWA loci in Cantabria (Middle North Spain) J. Forensic Sci 2000 45 Santos S.M Simoes F Armada A Clemente A Correia M.C HLA-DQA1 polymorphism in two Portuguese population samples from Lisbon and the South of Portugal Advance Forensic Haemogenet 1996 a 6 Santos S.M Simoes F Armada A Clemente A Correia M.C D1S80 locus polymorphism in a population sample from Lisbon Advance. Forensic Haemogenet 1996 b 6 Satoh K Takahashi K Itoh Y Kobayashi R Typing of DNA using the primer extension preamplification (PEP) method-studies of reliability of typing and detection limits [Japanese] Nippon Hoigaku Zasshi 1998 52 Scholl S Budowle B Radecki K Salvo M Navajo, Pueblo, and Sioux population data on the Loci HLA-DQA1, LDLR, GYPA, HBGG, D7S8, Gc, and D1S80 J. Forensic Sci 1996 41 Sebetan I.M Hajar H.A HLA DQ alpha genotype and allele frequencies in Qatari population Forensic Sci. Int 1997 90 Sebetan I.M Hajar HA Isobe E Frequency distribution of D1S80 (MCT118) locus polymorphism in a Qatari population Hum. Biol 1998 70 Shapiro R La impronta humana La impronta humana 1993 Madrid Acento Editorial Sirchia S.M Garagiola I De Andreis C Gazzoli I Gramegna M Colucci G Characterization of four microsatellites in an Italian population and their application to paternity testing Mol. Cell Probes 1996 10 Soares-Vieira J.A Billerbeck A.E.C Iwamura E.S.M Muñoz D.R Otto P.A Allele and genotype frequencies for D1S80 locus in a Brazilian population sample J. Forensic Sci 2000 45 Soares-Vieira J.A Billerbeck A.E.C Iwamura E.S.M Otto P.A Muñoz D.R Gene and genotype frequencies for HLA-DQA1 in Caucasians and mulattoes in Brazil J. Forensic Sci 1999 44 Soares-Vieira J.A Munoz D.R Iwamura E.S Billerbeck A.E Otto PA Allele frequency distribution of three STR loci (CSF1PO, TPOX, and TH01) in a Brazilian population sample J. Forensic Sci 2001 46 Spinella A Marsala P Biondo R Montagna P Italian population allele and genotype frequencies for the AmpliType PM and the HLA-DQ-alpha loci J. Forensic Sci 1997 42 Sueblinvong T Sirisup N Anomasiri W Kongsrisook U Sueblinvong T Population genetic data on loci LDLR, GYPA, HBGG, D7S8 and GC in the Bangkok population compared with rural Thais from Trat province J. Med. Assoc. Thai 1999 82 Tagliabracci A Giorgetti R Agostini A Buscemi L Cingolani M Ferrara S.D Frequency of HLA DQA1 alleles in an Italian population Int. J. Legal Med 1992 105 Tagliabracci A Buscemi L Cerri N Cucurachi N Lombardi R Mignola R Neri T.M Vecchiotti C De Ferrari F Masotti G Rodriguez D Umani Ronchi G Italian population data on the loci LDLR, GYPA, HBGG, D7S8 and GC Int. J. Legal Med 1996 109 Tahir M.A al Khayat A.Q al Shamali F Budowle B Novick G.E Distribution of HLA-DQA1 alleles in Arab and Pakistani individuals from Dubai, United Arab Emirates Forensic Sci. Int 1997 a 85 Tahir M.A Caruso J Budowle B Aziz N Novick G.E Distribution of HLA-DQ alpha and polymarker (LDLR, GC, GYPA, HBGG, and D7S8) alleles in Arab and Pakistani populations living in Abu Dhabi, United Arab Emirates J. Forensic Sci 1997 b 42 Tahir M.A Herrera R.J Khan A.A Kashyap V.K Duncan G Barna C Budowle B Rowold D.J Amjad M Sinha S Distribution of HLA-DQA1, polymarker, CSF1PO, vWA, TH01, TPOX, D16S539, D7S820, D13S317, and D5S818 alleles in East Bengali and West Punjabi populations from Indo-Pak Subcontinent J. Forensic Sci 2000 45 Trabetti E Galavotti R Casartelli A Magalini G De Leo D Pignatti P.F Allele and genotype frequencies of eight DNA polymorphisms in the Italian population Mol. Cell Probes 1995 9 Trivedi R Chattopadhyay P Kashyap V.K A new improved method for extraction of DNA from teeth for the analysis of hypervariable loci Am. J. Forensic Med. Pathol 2002 23 Tomsey C.S Basten C.J Budowle B Giles B.A Ermlick S Gotwald S Use of combined frequencies for RFLP and PCR based loci in determining match probability J. Forensic Sci 1999 44 Turowska B Sanak M Data on the loci LDLR, GYPA, HBGG, D7S8 and GC in a south Polish population Int. J. Legal Med 1998 111 Uinuk-Ool T.S Takezaki N Sukernik R.I Nagl S Klein J Origin and affinities of indigenous Siberian populations as revealed by HLA class II gene frequencies Hum. Genet 2002 110 Ulkuer M.K Ulkuer U Kesici T Menevse A Data on the PCR Turkish population based loci: LDLR, GYPA, HBGG, D7S8, and Gc J. Forensic Sci 1999 44 Vural B Atlioglu E Kolusayin O Togan I Buyukdevrim S Ozcelik T Turkish population data on the HLA-DO alpha, LDLR, GYPA, HBGG, D7S8, and GC loci Int. J. Legal Med 1998 111 Walkinshaw M Strickland L Hamilton H Denning K Gayley T DNA profiling in two Alaskan Native populations using HLA-DQA1, PM, and D1S80 loci J. Forensic Sci 1996 41 Watanabe Y Yamada S Nagai A Takayama T Hirata K Bunai Y Ohya I Japanese population DNA typing data for the loci LDLR, GYPA, HBGG, D7S8, and GC J. Forensic Sci 1997 42 Wolfarth R Nhari L.T Budowle B Kanoyangwa S.B Masuka E Polymarker, HLA-DQA1 and D1S80 allele data in a Zimbabwean Black sample population Int. J. Legal Med 2000 113 Woller J Budowle B Furedi S Padar Z Hungarian population data on the loci HLA-DQ alpha, LDLR, GYPA, HBGG, D7S8 and GC Int. J. Legal Med 1996 108 Woo K.M Budowle B Korean population data on the PCR-based loci LDLR, GYPA, HBGG, D7S8, Gc, HLA-DQA1, and D1S80 J. Forensic Sci 1995 40 Yamamoto T Uchihi R Kojima T Nozawa H Huang X.L Tamaki K Katsumata Y Maternal identification from skeletal remains of an infant kept by the alleged mother for 16 years with DNA typing J. Forensic Sci 1998 43 3 Yasin S.R Hamad M el Karmi A Jordanian population data on the PCR-based loci: LDLR, GYPA, HBGG, D7S8 and GC Forensic Sci. Int 1999 104 Yunis J.J Garcia O Baena A Arboleda G Uriarte I Yunis E Population frequency for the short tandem repeat loci D18S849, D3S1744, and D12S1090 in Caucasian-Mestizo and African descent populations of Colombia Forensic. Sci. Int 2000 a 45 Yunis J.J Garcia O Uriarte I Yunis E.J Population data on 6 short tandem repeat loci in a sample of Caucasian-Mestizos from Colombia Int. J. Legal Med 2000 b 113 Yunis J.J Garcia O Uriarte I Yunis E.J Population data on D16S539, D7S820, D13S317, LPL, F13B and D1S80 loci in a sample of Caucasian-Mestizos from Colombia Forensic Sci. Int 2001 115 Zehner R Mebs D Bratzke H Population genetic study of the simultaneously amplified loci HLA DQA1, LDLR, GYPA, HBGG, D7S8, and GC in a German population sample J. Forensic Sci 1998 43
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300031 Genotype profiles for the Costa Rican population at 7 PCR-based loci Morera Bernal Morales C Ana Isabel Jiménez-Arce G ,Poder Judicial Heredia Costa Rica ,Universidad de Costa Rica ,Universidad de Costa Rica Costa Rica 09 2004 2004 52 713 715

Complete electronic DNA profiles of 2006 randomly selected Costa Ricans, typed for 7 PCR-based loci, are presented. Such data may prove valuable for anthropological and forensic studies of the Costa Rican population. Rev. Biol. Trop. 52(3): 713-715. Epub 2004 Dic 15.

Se presenta una versión electrónica de los perfiles genéticos completos de 2006 individuos de Costa Rica seleccionados al azar, quienes fueron caracterizados para loci 6 basados en PCR. Tales datos podrían ser valiosos para estudios antropológicos y forenses de la población costarricense.

 Forensic electronic communication DNA profiles PCR-based loci Costa Rica Ciencias Forenses datos electrónicos ADN PCR Costa Rica Aler M Salas A Sanchez-Diz P Murcia E Carracedo A Gisbert M Y-chromosome STR haplotypes from a Western Mediterranean population sample Forensic Sci. Int 2001 119 Bosch E Lee A.C Calafell F Arroyo E Henneman P de Knijff P Jobling M.A High resolution Y chromosome typing: 19 STRs amplified in three multiplex reactions Forensic Sci. Int 2002 125 Berardi G Toscanini U Raimondi E STR data for the PowerPlex 16 loci system from Buenos Aires population, Argentina Forensic Sci. Int 2003 134 Budowle B Shea B Niezgoda S Chakraborty R CODIS STR loci data from 41 sample populations J. Forensic Sci 2001 46 Budowle B Moretti T. R Genotype Profiles for Six Population Groups at the 13 CODIS Short Tandem Repeat Core Loci and Other PCRBBased Loci Forensic Science Communications 1999 Vol.1 2 Chiurillo M.A Morales A Mendes A.M Lander N Tovar F Fuentes A Ramirez J.L Genetic profiling of a central Venezuelan population using 15 STR markers that may be of forensic importance Forensic Sci. Int 2003 136 Cifuentes L Acuna M Sepulveda D Allele frequencies for six STR in a Chilean population J. Forensic Sci 2002 47 Gómez J Carracedo A The 1998-1999 collaborative exercises and proficiency testing program on DNA typing of the spanish and portuguese working group of the international society for forensic genetics (GEP-ISFG) Forensic Sci. Int 2000 114 Gonzalez-Andrade F Sanchez D Martinez-Jarreta B Genetic profile of the Ecuadorian mestizo population (Ecuador-South America) by using the PowerPlex 16 loci system kit Forensic Sci. Int 2003 135 Grattapaglia D Schmidt A.B Costa e Silva C Stringher C Fernandes A.P Ferreira ME Brazilian population database for the 13 STR loci of the AmpFlSTR Profiler Plus and Cofiler multiplex kits Forensic Sci. Int 2001 118 Gusmao L Sanchez-Diz P Alves C Lareu M.V Carracedo A Amorim A Genetic diversity of nine STRs in two northwest Iberian populations: Galicia and northern Portugal Int. J. Legal Med 2000 114 Jobling M.A Y-chromosomal SNP haplotype diversity in forensic analysis Forensic Sci. Int 2001 118 Luna-Vazquez A Vilchis-Dorantes G Paez-Riberos L.A Muñoz-Valle F Gonzalez-Martin A Rangel-Villalobos H Population data of nine STRs of Mexican-Mestizos from Mexico City Forensic Sci. Int 2003 136 Morales J.A Monterrosa J.C Alvarez J.C Entrala C Lorente J.A Lorente M Budowle B Villanueva E Population data on nine STR loci in an El Salvadoran (Central American) sample population J. Forensic Sci 2002 47 Morales C A.I Morera B Jiménez-Arce G Proyecto Implantar en Costa Rica la detección de huellas genéticas humanas para la identificación individual en casos criminalisticos y de paternidad. Informe Final Rev. Latinoam. Der. Méd. y Med. Legal 1997 8 2 Morales-Cordero A.I Morera B Jiménez-Arce G Sánchez-Rivera G Calafell F Barrantes R Allele frequencies of the markers LDLR, GYPA, HBGG, D7S8, Gc, HLA-DQA1, and D7S80 in the general and minority populations of Costa Rica Forensic Sci. Int 2001 124 Morales C A.I Morera B Jiménez-Arce G La implementación forense de la tecnología del ADN en Costa Rica: Un análisis retrospectivo Rev. Biol. Trop 2004 52 Morera B Análisis del Polimorfismo del ADNmt en la Población General de Costa Rica: Un Asunto Pendiente Rev. Latinoam. Der. Méd. y Med. Legal 2001 /2 6/7 Morera B Jiménez-Arce G Identificación de restos óseos mediante análisis de ADN Med. Legal Costa Rica 1998 15 Morera B Marín-Rojas R Barrantes R Análisis de varios marcadores genéticos clásicos en la población de Costa Rica Rev. Biol. Trop 2001 a 49 Morera B Sánchez-Rivera G Jiménez-Arce G Calafell F Morales-Cordero A.I Nicaraguan population data on LDLR, GYPA, HBGG, D7S8, Gc, and HLA-DQA1 loci Rev. Biol. Trop 2001 b 49 Morera B Marín-Rojas R Barrantes R Gene Admixture in the Costa Rican Population Ann. Hum. Genet 2003 67 Olaisen B Bar W Brinkmann B Budowle B Carracedo A Gill P Lincoln P Mayr W.R Rand S DNA recommendations 1997 of the International Society for Forensic Genetics Vox Sang 1998 74 Pagano S Alvarez J.C Entrala C Lorente J.A Lorente M Budowle B Villanueva E Uruguayan population data for eight STR loci (using the PowerPlex 1.2 kit) J. Forensic Sci 2001 46 Paredes M Galindo A Bernal M Avila S Andrade D Vergara C Rincon M Romero R.E Navarrete M Cardenas M Ortega J Suarez D Cifuentes A Salas A Carracedo A Analysis of the CODIS autosomal STR loci in four main Colombian regions Forensic Sci. Int 2003 137 Perez L Hau J Izarra F Ochoa O Zubiate U Garcia O Allele frequencies for the 13 CODIS STR loci in Peru Forensic Sci. Int 2003 132 Perez-Lezaun A Calafell F Clarimon J Bosch E Mateu E Gusmao L Amorim A Benchemsi N Bertranpetit J Allele frequencies of 13 short tandem repeats in population samples from the Iberian Peninsula and northern Africa Int. J. Legal Med 2000 113
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300032 Comparación de tres métodos de extracción de ADN a partir de restos óseos Del Valle Christian Rodríguez Anayanci Espinoza Marta ,Organismo de Investigación Judicial Heredia Costa 09 2004 2004 52 717 725

Comparison of three methods for DNA extraction from bone remains. Extraction of amplifiable DNAis a frequent problem when working with degraded specimens like bone samples. The possibility of obtaining as much information as possible from these samples has a particular significance in many forensic investigations. The present investigation was aimed to assess the efficiency of three organic extraction methods for purifying amplifiable DNA from bone samples. The amount of nucleic acids obtained, the success rate in the amplification of DNA microsatellite (STR) markers and amelogenin by PCR, the influence of PCR inhibitors and environmental conditions, and where the samples were found before their processing in the laboratory, were all evaluated in this investigation for the three methods. Results showed that method A (a modification of FBI method for DNA extraction) performed better in producing not a higher amount but a better quality amplifiable DNA, in comparison with the other two methods evaluated. It was also demonstrated that the quality of the DNA to be amplified by PCR was influenced by the presence of inhibitors and/or contaminants and the environmental conditions where the bone sample was taken from. The worst conditions were observed from aquatic environments. The results suggest that the implementation of some specific modifications in the method A (use of purification columns, reliable quantification methods and different dilutions) would help to obtain better DNA extracts intended to be used in different molecular identification tests. Rev. Biol. Trop. 52(3): 717-725. Epub 2004 Dic 15.

Diferentes investigaciones han demostrado que la posibilidad de llevar a cabo estudios de marcadores genéticos está muchas veces limitada por la capacidad de obtener ácidos desoxirribonucleicos (ADN) a partir de muestras degradadas como los restos óseos. Asu vez, la información que de allí se derive resulta de suma importancia en diferentes situaciones médico-legales. El presente estudio se diseñó para comparar la eficiencia de tres métodos orgánicos de extracción de ADN amplificable por la técnica de Reacción en cadena de la Polimerasa (PCR) a partir de muestras de hueso. En esta investigación se procedió a evaluar, comparativamente, la cantidad de ácidos nucleicos obtenidos, el éxito en la amplificación de marcadores microsatélites (STR) y amelogenina por PCR, la posible presencia de inhibidores y el contexto de donde provenían las muestras para los tres métodos. Una modificación del método de extracción utilizado por el FBI (Federal Bureau of Investigation) de los Estados Unidos, denominado método A, aunque no produjo la mayor cantidad de ADN, mostró el mejor rendimiento en cuanto a la calidad requerida para la amplificación por PCR. A la vez, se demostró que dicho rendimiento es influenciado por la posible presencia de inhibidores o contaminantes y por el contexto en el cual permanecieron las muestras previo a su análisis en el laboratorio. Los hallazgos sugieren que la introducción de algunas modificaciones específicas al método A (la incorporación de columnas de purificación, la cuantificación específica de ADN humano en los extractos y el uso de diluciones) podría mejorar sustancialmente el rendimiento de este método de extracción para que pueda ser utilizado con mayor éxito en diferentes investigaciones médico-legales que requieran la disponibilidad de ADN en calidad y cantidad adecuadas.

 DNA extraction PCR STRs bones inhibitors Costa Rica Extracción ADN PCR hueso STRs inhibidores Costa Rica GenePrint &trade; STR Systems(Silver Stain Detection). Technical Manual GenePrint &trade; STR Systems(Silver Stain Detection). Technical Manual 1994 -1 99 ^eWI Promega Co. Madison Buttler J Forensic DNA Typing; Biology & Technology behind STR Markers Forensic DNA Typing; Biology & Technology behind STR Markers 2001 ^eCalifornia Academic Cattaneo C. Craig James O Sokol, R N Comparison of Three DNA Extraction Methods on Bone and Blood Stains up to 43 years old and Amplification of Three Different Gene Frequencies J. Forensic Sci 1997 42 Fawcett D Tratado de Histología Tratado de Histología 1990 Nueva Editorial Interamericana, S.A Higuchi R Von Beroldingen C.H Sensabaugh GF Erlich HA DNA typing from single hairs Nature 1988 332 Hochmeister M.N Bodowle B Borer U.V Rudin O Bohnert M Dirnhofer R Confirmation of the identity of human skeletal remains using multiplex PCR amplification and typing kit J. Forensic Sci 1995 40 Hochmeister M.N Budowle B Borer UV Eggman U Comey C.E Dirnhofer R Typing of deoxyrribonucleic acid (DNA) extracted from compact bone from human remains J. Forensic Sci 1991 36 Jiménez-Arce G Morera B Revisión sobre la extracción de ADN a partir de huesos humanos Med. Legal Costa Rica 1999 16 1/2 Lassen C Hummel S Herrman B PCR Based Sex Identification of Ancient Human Bones by Amplification of X- and Y- Chromosomal Sequences: A Comparison Ancient Biomolecules. (Netherlands) 1996 1 1 Lindahl T Instability and decay of the primary structure of DNA Nature 1993 362 Maniatis T Fritsch EF Sambrook J Molecular cloning: a laboratory manual Molecular cloning: a laboratory manual 1982 ^eNew York Cold Spring Harbor Lab Matamoros M Frecuencias alélicas de los loci de repeticiones cortas en tandem en la población hondureña: su aplicación forense Frecuencias alélicas de los loci de repeticiones cortas en tandem en la población hondureña: su aplicación forense 1999 Morales C A.I Morera B Jiménez-Arce G La implementación forense de la tecnología del ADN en Costa Rica: Un análisis retrospectivo Rev. Biol. Trop 2004 52 3 Miesfeld R Applied Molecular Genetics Applied Molecular Genetics 1999 John WileyNew York Morera B Jiménez-Arce G Identificación de restos óseos mediante análisis de ADN Med. Legal Costa Rica 1998 15 1/2 Morera B Marín R Barrantes R Análisis de varios marcadores genéticos clásicos en la población de Costa Rica Rev. Biol. Trop 2001 49 Nakamura Y Variable number of tandem repeats (VNTR) markers for human gene mapping Science 1987 235 Rojas E Análisis de marcadores polimórficos de ADN para pruebas de identidad Análisis de marcadores polimórficos de ADN para pruebas de identidad 1995 Schultz D.J Craig R Cox-Foster D.L Mumma R.O Medford J.I RNA isolation from recalcitrant plant tissue Plant Mol. Biol. Rep 1994 12
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300033 Relación de los cultivos modificados genéticamente con el ambiente y la salud de la población costarricense Espinoza Ana M Arrieta-Espinoza Griselda Sittenfeld Ana ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 727 732

Relationship of genetically modified crops with the environment and health of the Costa Rican human population. Genetic engineering and the food derived from genetically modified crops (GMCs) have been the center of debate worldwide, as has occurred historically with the advent of new technologies. Questions are derived from the potential impact of GMCs to the environment and the safety of the products to the consumers. In relation to the first inquiry, practice has been oriented to a case-by-case-study, according to the own characteristics of the GMC, in order to minimize its impact in the environment. Scientific studies in diverse latitudes of the world have demonstrated that GMCs in the market showed no adverse effects related to this issue. In relation to food derived from the GMCs, rigorous evaluation protocols have been developed and approved by FAO and WHO to guarantee the innocuousness of these products. Up to the moment, no contraindications for human health have been pointed out for the products that are available today in the market. In the particular case of Costa Rica, the country has established since the 90s a regulatory biosafety framework for the management of the GMCs, safeguarding the biodiversity of the country and the health of consumers. At the same time the country has made significant public and private investments in the field that allowed the country to obtain a leading position in biosafety in the region and genetic engineering research at national research centers. Any attempt to restrict or prohibit these activities in the country, will put in risk the previously described investment, will affect the generation of new knowledge for decision making and the leadership in the field, preventing the benefits derived from this promising technology. Rev. Biol. Trop. 52(3): 727-732. Epub 2004 Dic 15.

La ingeniería genética y los alimentos derivados de los cultivos genéticamente modificados (CGMs) han sido objeto de debate a escala mundial, como ocurre históricamente con el surgimiento de tecnologías novedosas. Se cuestiona si los CGMs son seguros al ambiente y si los productos derivados de ellos son inocuos para los consumidores. Sobre la primera de esas inquietudes, la práctica se ha orientado a estudiar caso por caso, según las propias características del CGM, para minimizar su impacto en el ambiente. Estudios científicos en diversas latitudes han demostrado que no ha habido efectos dañinos en este particular. En cuanto a los alimentos derivados de los CGMs se han desarrollado sistemas de evaluación rigurosa para permitir su consumo y comercialización, y hay protocolos aprobados por la FAO y la OMS para garantizar su inocuidad. Hasta el momento, en ningún caso se han detectado contraindicaciones para la salud humana en los productos disponibles hoy en el mercado. Por su parte, Costa Rica estableció desde los años 90 un marco regulatorio en bioseguridad que se encarga de garantizar la seguridad para la salud y el ambiente en el manejo de los CGMs. Asimismo, se ha hecho una gran inversión estatal y privada en esta área, lo que le permitió a Costa Rica posicionarse en la región como uno de los primeros países con fortalezas en materia de bioseguridad y de investigación en ingeniería genética en centros de investigación nacionales. Cualquier intento de restringir o prohibir dicha actividad pondría en riesgo esa inversión, afectaría la generación de nuevo conocimiento para la toma de decisiones y el liderazgo alcanzado en el campo y nos privaría de los beneficios de esta prometedora tecnología.

 transgenics GMCs Costa Rica biosafety regulatory framework transgénicos OGMs Costa Rica bioseguridad marco regulatorio Arrieta G Quesada T Gamboa E Sánchez E Espinoza A.M Roseland C.R Transgenic rice and gene flow assessment to wild and weedy rice species in Costa Rica Abstracts of the OECD International Conference LMOS and the Environment, held in Raleigh, North Carolina, USA Abstracts of the OECD International Conference LMOS and the Environment, held in Raleigh, North Carolina, USA 2002 Arrieta-Espinoza G Sánchez E Vargas S Lobo J Quesada T Espinoza A.M The weedy rice complex in Costa Rica. I. Morphologic study and relationship with comercial rice varieties and wild Oryza relatives Genet. Resources Crop Evol 2004 Atanassov A Bahieldin A Brink J Burachik M Cohen J.I Dhawan V Ebora R.V Falck-Zepeda J Herrera-Estrella L Komen J Low F. C Omaliko E Odiambo B Quemada H Peng Y Sampaio M.J Sithole-Niang I Sittenfeld A Smale M Valyasevi R Zafar Y Zambrano P To Reach the Poor - Results from the ISNAR-IFPRI Next Harvest Study on Genetically Modified Crops, Public Research, and Policy Implications. EPTD Discussion Paper No. 116 To Reach the Poor - Results from the ISNAR-IFPRI Next Harvest Study on Genetically Modified Crops, Public Research, and Policy Implications. EPTD Discussion Paper No. 116 2004 ^eWashington D.C International Food Policy Research Institute IFPRI Borlaug N.E Ending world hunger. The promise of biotechnology and the threat of antiscience zealotry Plant Physiol 2000 124 Burke J.M Rieseberg L.H Fitness effects of transgenic disease resistance in sunflowers Science 2003 300 Conner A.J Glare T.R Nap J-P The release of genetically modified crops into the environment. Part II. Overview of ecological risk assessment Plant J 2003 33 Conway G Toenniessen G Feeding the world in the twenty-first century Nature 1999 402 Daniell H New tools for chloroplast genetic engineering Nat. Biotech 1999 17 Ellstrand N.C Prentice H.C Hancock J.F Gene flow and introgression from domesticated plants into their wild relatives Ann. Rev. Ecol. Syst 1999 30 Espinoza A.M Sittenfeld A Salazar S Developing transgenic rice at the University of Costa Rica: perspectives and considerations for managing intellectual property rights Interciencia 2003 28 Safety aspects of genetically modified foods of plant origin. Report of a joint FAO/WHO expert consultation on foods derived from biotechnology, WHO, Geneva, Switzerland, (Geneva: WHO) Safety aspects of genetically modified foods of plant origin. Report of a joint FAO/WHO expert consultation on foods derived from biotechnology, WHO, Geneva, Switzerland, (Geneva: WHO) 2000 Hails R.S Assessing the risks associated with new agricultural practices Nature 2002 418 Haslberger A.G GM food: The risk assessment of immune hypersensitivity reactions covers more than allergenicity Food Agr. Environ 2003 1 Huang J Pray C Roselle S Enhancing the crops to feed the poor Nature 2002 418 Kuiper H.A Kleter G.A Noteborn H.P.J.M Kok E.J Assesment of the food safety issues related to genetically modified foods Plant J 2001 27 Kuiper H.A Comparative safety assessment for biotech crops Trends Biotechnol 2003 21 The use of genetically modified crops in developing countries. A follow- up discussion paper The use of genetically modified crops in developing countries. A follow- up discussion paper 2004 Qaim M Zilberman D Yield effects of genetically modified crops in developing countries Science 2003 299 Quesada T Lobo J Espinoza A.M Genetic diversity and mating system of the wild rice species Oryza Latifolia Desv. Genet. Resources Crop Evol 2002 49 Ramón D Presente y futuro de los alimentos transgénicos Sistema 2004 179-180 Sittenfeld A Espinoza A. M Muñoz M Zamora A Presley G.J MacIntyre L.R Costa Rica Agricultural Biotechnology: Country Case Studies-A Decade of Development Agricultural Biotechnology: Country Case Studies-A Decade of Development 2001 CABI Valdez M López R Jiménez L Estado actual de la biotecnología en Costa Rica Rev. Biol. Trop 2004 a 52 Valdez M Madriz K Ramírez P Establecimiento de un método de transformación genética de maíz para conferirle resistencia ulterior a enfermedades virales Rev. Biol. Trop 2004 b 52 Valdez M Rodríguez I Sittenfeld A Percepción de la biotecnología en estudiantes universitarios de Costa Rica Rev. Biol. Trop 2004 c 52 Zamora-Meléndez A González P Espinoza A.M Wild rice (Poaceae: Oryza) species of Costa Rica: diversity and distribution Genet. Resources Crop Evol 2003 50 Arjona R May A Desarrollo de un Marco Nacional en Bioseguridad para Costa Rica Proyecto UNEP-GEF Proyecto UNEP-GEF 2004 BIO’s Editors’ and Reporters’ Guide to Biotechnology. 2002-2003 BIO’s Editors’ and Reporters’ Guide to Biotechnology. 2002-2003 2002 New genetics, food and agriculture: Scientific Discoveries-Societal Dilemas (France: ICSU) New genetics, food and agriculture: Scientific Discoveries-Societal Dilemas (France: ICSU) 2003 James C Preview-global starus of commercialized transgenic crops. (ISAAA Briefs No 30) Preview-global starus of commercialized transgenic crops. (ISAAA Briefs No 30) 2003 Gerencia Técnica de Biotecnología Gerencia Técnica de Biotecnología 2004 Plant biotechnology: current and potential impact or improving pest management in U.S. agriculture: An analysis of 40 case studies Plant biotechnology: current and potential impact or improving pest management in U.S. agriculture: An analysis of 40 case studies 2002 20 questions on genetically modified (GM) foods 20 questions on genetically modified (GM) foods 2003
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300034 Estado actual de la biotecnología en Costa Rica Valdez Marta López Rebeca Jiménez Luis ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica 09 2004 2004 52 733 743

Current estate of biotechnology in Costa Rica. Astudy was carried out on the construction of indicators in biotechnology in Costa Rica as part of the project "SYMBIOSIS, Cooperative Program for the Construction of Indicators in Biotechnology adapted to Latin American and Caribbean countries, to motivate the application and transference of industrial technologies". The study focused on two units: researchers and research projects developed in Costa Rica, between 1998 and 2002. For researchers, information was collected about indicators related to sex, age, teaching activities, number of projects, academic degree, area of speciality and number of publications. For research projects we obtained information about: speciality, sector of application, duration of projects and number of researchers per project. Very interesting results include the high participation of the women in this area of investigation (54%); the low participation of young researchers (13% younger than 30), and a high proportion of the investigators that are responsible for 4 or more projects (42%). With relation to the specialities of the projects, the majority are in the category Bio-Agro (39%) whereas in Acuaculture only 1 % was found. The sectors of application with the most number of projects are: Agriculture and Livestock (37%) and Human Health (35%). The main strengthts and limitatations for the development of biotechnology in Costa Rica are discussed. Rev. Biol. Trop. 52(3): 733-743. Epub 2004 Dic 15.

Se realizó un estudio del estado de la biotecnología en Costa Rica como parte del proyecto "SIMBIOSIS: Programa Cooperativo para la Construcción de Indicadores en Biotecnología adaptados a los países de América Latina y el Caribe, para motivar la aplicación y transferencia de tecnologías industriales". El estudio se enfocó en dos ítemes: "investigadores" y "proyectos de investigación", desarrollados en Costa Rica entre 1998 y 2002. Se construyó una base de datos a partir de la cual se obtuvieron indicadores para los investigadores, relacionados con aspectos como género, edad, desempeño como docentes, número de proyectos, funciones, grado académico, área de especialidad y número de publicaciones. Los indicadores determinados para los proyectos de investigación se vinculan con los temas de: especialidades, sector socioecónomico de aplicación, duración y número de investigadores por proyecto. Entre las principales conclusiones obtenidas a nivel nacional cabe mencionar la alta participación de las mujeres en esta área de investigación (54%); la baja participación de recursos humanos jóvenes como investigadores (13% menores de 30 años), y que la mayoría de los investigadores, con altos grados académicos, tienen 4 o más proyectos a su cargo (42%). Con relación a las especialidades de los proyectos, la mayoría se clasifican en la categoría Bio-Agro (39%) mientras que en Acuicultura sólo se encontró un 1% del total. Los sectores de aplicación con el mayor número de proyectos son: Agropecuario (37%) y Salud Humana (35%). Se discuten las principales fortalezas y limitaciones para el desarrollo de la biotecnología en Costa Rica, para contribuir a una mejor definición de políticas de desarrollo científico y tecnológico del país.

 Costa Rica Biotechnology Agricultural biotechnology Human health Indicators Costa Rica Biotecnología Indicadores Biotecnología agrícola Salud humana Arias O Komen J Falconi C Hernández H Addressing market needs through biotechnology: the example of Agribiotecnología de Costa Rica Agricultural Biotechnology Policy Seminar Agricultural Biotechnology Policy Seminar 1999 Intermediary Biotechnology Service/CamBioTec Arjona R May A Desarrollo de un Marco Nacional en Bioseguridad para Costa Rica Proyecto UNEP-GEF Proyecto UNEP-GEF 2004 Estado de la Nación en Desarrollo Humano Sostenible Estado de la Nación en Desarrollo Humano Sostenible 2003 Gerencia Técnica de Biotecnología Gerencia Técnica de Biotecnología 2004 Programa BID II. Biotecnología, justificación de subáreas. Costa Rica, Febrero de 2003 Programa BID II. Biotecnología, justificación de subáreas. Costa Rica, Febrero de 2003 2003 Sasson A Les biotechnologies: defis et promesses Les biotechnologies: defis et promesses 1985 Paris U.N.E.S.C.O Sasson A Biotechnologies and development Biotechnologies and development 1988 Paris UNESCO, Technical Centre for Agricultural and Rural Cooperation (CTA) Sasson A Biotechnologies in perspective: Socioeconomic implications for developing countries Biotechnologies in perspective: Socioeconomic implications for developing countries 1991 UNESCO, Presses Universitaires de France Serageldin I Biotechnology and food security in the 21st century Science 1999 285 Solleiro J. L Castañón R Verástegui J La Biotecnología en América Latina: panorama al año 2002 CamBioTec, Iniciativa Canadiense- Latinoamericana en Biotecnología para el Desarrollo Sustentable CamBioTec, Iniciativa Canadiense- Latinoamericana en Biotecnología para el Desarrollo Sustentable 2002 IDRC Testa P Indicadores de las capacidades de investigación en biotecnología: análisis comparativo de Colombia, Costa Rica, México y Venezuela. Programa Cooperativo para la Costrucción de Indicadores en Biotecnología y Tecnología de Alimentos: Taller de Indicadores en Biotecnología, Bogotá, Colombia, Noviembre de 2003 Indicadores de las capacidades de investigación en biotecnología: análisis comparativo de Colombia, Costa Rica, México y Venezuela. Programa Cooperativo para la Costrucción de Indicadores en Biotecnología y Tecnología de Alimentos: Taller de Indicadores en Biotecnología, Bogotá, Colombia, Noviembre de 2003 2003 Programa Institucional de Biotecnología: 2001-2004 Programa Institucional de Biotecnología: 2001-2004 2001 San José Comisión Institucional de Biotecnología, Vicerrectoría de Investigación Valdez M Sittenfeld A Current State of Modern Agricultural Biotechnology in Costa Rica Current State of Modern Agricultural Biotechnology in Costa Rica 2002 Paris OECD Global Forum on Knowledge Economy - Biotechnology Ver van Beuzekom B Biotechnology Statistics in OECD Member Countries: Compendium of Existing National Statistics Biotechnology Statistics in OECD Member Countries: Compendium of Existing National Statistics 2001 Organisation for Economic Cooperation and Development, Directorate for Science, Technology and Industry STI Working Papers Zeledón R Significado de la nueva biotecnología para América Latina y el Caribe. La nueva biotecnología en agricultura y salud Significado de la nueva biotecnología para América Latina y el Caribe. La nueva biotecnología en agricultura y salud 1988 San José Instituto Interamericano de Cooperación para la Agricultura, (IICA)
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300035 Percepción de la biotecnología en estudiantes universitarios de Costa Rica Valdez Marta Rodríguez Iris Sittenfeld Ana ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 745 756

Perception about biotechnology in university students in Costa Rica. A survey was carried out to determine the perception and knowledge about biotechnology and genetically modified organisms (GMOs) in a sample (n = 750) of university students from three public universities in Costa Rica: Universidad de Costa Rica, Universidad Nacional and Instituto Tecnológico de Costa Rica. The study revealed that 88% of the students showed a satisfactory level of knowledge about modern biotechnology and 79% of them reported a favorable opinion and good acceptance of this technology. Students would accept some risks associated to biotechnology if it represents an improvement to the competitiveness of Costa Rica. Some differences were detected in the opinions from students of the three universities that can be associated to the area of study. Students from social disciplines showed a higher percentage of negative acceptances to biotechnology and GMOs when their opinions were compared with those of students from life sciences and technologies. Rev. Biol. Trop. 52(3): 745-756. Epub 2004 Dic 15.

Se llevó a cabo una encuesta para estudiar la percepción y el grado de conocimiento sobre biotecnología y organismos modificados genéticamente (OMGs), en una muestra de estudiantes (n=750) de tres universidades públicas de Costa Rica: Universidad de Costa Rica (UCR), Universidad Nacional (UNA) e Instituto Tecnológico de Costa Rica (ITCR). Se encontró que un 88% mostraron un conocimiento satisfactorio de la biotecnología moderna, y que un 79% expresaron una posición favorable y una buena aceptación de esa tecnología. Además, los estudiantes encuestados aceptarían ciertos riesgos asociados a la biotecnología, siempre y cuando, ésta mejore la capacidad competitiva de Costa Rica. El área de estudio de los estudiantes entrevistados parece estar relacionada con el grado de aceptación debido a que los estudiantes de disciplinas sociales mostraron una mayor percepción negativa hacia los productos biotecnológicos y OMGs, si se compara con la percepción expresada por los estudiantes encuestados de disciplinas de ciencias naturales y de áreas tecnológicas.

 Costa Rica biotechnology university students genetically modified organisms GMOs public perception Costa Rica biotecnología estudiantes universitarios organismos modificados geneticamente OMGs percepción pública Aerni P Assessing stakeholder attitudes to agricultural biotechnology in developing countries Biotechnol. Dev. Monitor 2001 47 Albertazzi F.J Scientific publications about DNA structure-function and PCR technique in Costa Rica: A historic view 1953-2003 Rev. Biol. Trop 2004 52 Cochran W. G Sampling techniques Sampling techniques 1963 ^eNew York Wiley Durant J Eurobarometer Proceedings of the international conference of the Council of Europe on ethical issues arising from the application of biotechnology. Oviedo, Spain, 16-19 May 1999 Proceedings of the international conference of the Council of Europe on ethical issues arising from the application of biotechnology. Oviedo, Spain, 16-19 May 1999 2000 Strasbourg Cedex Council of Europe Publishing Espinoza A.M Sittenfeld A Salazar S Developing transgenic rice at the University of Costa Rica: perspectives and considerations for managing intellectual property rights Interciencia 2003 28 Fritz S Husmann D Wingenbach G Rutherford T Egger V Wadhwa P Awareness and acepptance of biotechnology issues among youth, undergraduates, and adults AgBioForum 2003 6 Garita-Bonilla N Araya Incera M La Opinión pública como un espacio de diálogo Estado de la opinión pública costarricense: un análisis de los principales temas de conflicto Estado de la opinión pública costarricense: un análisis de los principales temas de conflicto 2001 San José CIMPA Gaskell G Allum N Bauer M Durant J Allansdottir A Bonfadelli H Boy D Cheveigné S Fjaestad B Gutteling J. M Hampel J JelsØe E Correia-Jesuino J Kohring M Kronberger N Midden C Nielsen T.H Przestalski A Rusanen T Sakellaris G Torgersen H Twardowsky T Wagner W Biotechnology and the European public Nat. Biotechnol 2000 18 Gaskell G Allum N Stares S Europeans and biotechnology in 2002. Eurobarometer 58.0. Areport to the EC Directorate General for Research from the project "Life Sciences in European Society" QLG7- CT-1999-00286 Europeans and biotechnology in 2002. Eurobarometer 58.0. Areport to the EC Directorate General for Research from the project "Life Sciences in European Society" QLG7- CT-1999-00286 2003 Gómez-Barrantes M Elementos de estadística descriptiva Elementos de estadística descriptiva 1998 San José Huete-Pérez J.A Orozco-González D Percepciones sobre biotecnología en Nicaragua ENCUENTRO 2001 58 Lang J. T O’Neill K.M Hallman W.K Expertise, trust and communication about food biotechnology AgBioForum 2003 6 Priest S.H US public opinion divided over biotechnology? Nat. Biotechnol 2000 18 Sasson A Les biotechnologies: defis et promesses Les biotechnologies: defis et promesses 1985 París U.N.E.S.C.O Sittenfeld A Espinoza A. M Costa Rica: revealing data on public perception of GM crops Trends Plant Sci 2002 7 Solleiro J.L Castañón R La Biotecnología en América Latina: panorama al año 2002. CamBioTec, Iniciativa Canadiense-Latinoamericana en Biotecnología para el Desarrollo Sustentable La Biotecnología en América Latina: panorama al año 2002. CamBioTec, Iniciativa Canadiense-Latinoamericana en Biotecnología para el Desarrollo Sustentable 2002 IDRC Trewavas A.J The population/biodiversity paradox. Agricultural efficiency to save wilderness Plant Physiol 2001 125 BIO’s Editors’ and Reporters’ Guide to Biotechnology. 2002-2003 BIO’s Editors’ and Reporters’ Guide to Biotechnology. 2002-2003 2002 James C Preview-global starus of commercialized transgenic crops. (ISAAA Briefs No 30) Preview-global starus of commercialized transgenic crops. (ISAAA Briefs No 30) 2003
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300036 Diversity of Bacillus thuringiensis strains isolated from coffee plantations infested with the coffee berry borer Hypothenemus hampei Arrieta Glen Hernández Alejandro Espinoza Ana M ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 757 764

The coffee berry borer Hypothenemus hampei Ferrari (Coleoptera: Scolytidae) was first reported infecting Costa Rican coffee plantations in the year 2000. Due to the impact that this plague has in the economy of the country, we were interested in seeking new alternatives for the biological control of H. hampei, based on the entomopathogenic bacteria Bacillus thuringiensis. Atotal of 202 B. thuringiensis isolates obtained from Costa Rican coffee plantations infested with H. hampei were analyzed through crystal morphology of the crystal inclusions and SDS-PAGE of d-endotoxins, while 105 strains were further evaluated by PCR for the presence cry, cyt and vip genes. Most of the Bt strains showed diverse crystal morphologies: pleomorphic (35%), oval (37%), bipyramidal (3%), bipyramidal and oval (12%), bipyramidal, oval and pleomorphic (10%) and bipyramidal, oval and cubic (3%). The SDS-PAGE analyses of the crystal preparations showed five strains with delta -endotoxin from 20 to 40 kDa, six from 40 to 50 kDa, seven from 50 to 60 kDa, 19 from 60 to 70 kDa, 29 from 70 to 100 kDa and 39 from 100-145 kDa. PCR analyses demonstrated that the collection showed diverse cry genes profiles having several genes per strain: 78 strains contained the vip3 gene, 82 the cry2 gene, 45 the cry1 and 29 strains harbored cry3-cry7 genes. A total of 13 strains did not amplified with any of the cry primers used: cry1, cry2, cry37, cry5, cry11, cry12 and cry14. Forty-three different genetic profiles were found, mainly due to the combination of cry1A genes with other cry and vip genes. The genetic characterization of the collection provides opportunities for the selection of strains to be tested in bioassays against H. hampei and other insect pests of agricultural importance. Rev. Biol. Trop. 52(3): 757-764. Epub 2004 Dic 15.

En el año 2000 se reportó por primera vez la principal plaga del cafeto, conocida como broca (Hypothenemus hampei Ferrari) (Coleoptera: Scolitidae) en plantaciones de este cultivo en Costa Rica. Debido al impacto que esta plaga tiene en la economía del país, surgió la necesidad de encontrar una alternativa para el control biológico de esta plaga, basadas en la bacteria entomopatógena Bacillus thuringiensis. El objetivo de este trabajo fue aislar y caracterizar cepas de Bacillus thuringiensis a partir de plantaciones de café infestadas con H. hampei. Se aislaton 202 cepas que se analizaron mediante la morfología del cristal, SDS-PAGE de las delta -endotoxinas, mientras que 105 cepas se evaluaron mediante PCR para determinar la presencia de genes cry, cyt y vip. La mayoría de las cepas presentaron diversas morfologías del cristal: pleomórficos (35%), ovalados (37%), bipiramidales (3%), bipiramidales y ovalados (12%), bipiramidales, ovalados y pleomórficos (10%) y bipiramidales, ovalados y cúbicos (3%). El análisis electorforético de las proteínas mostró que 5 cepas contenían delta -endotoxinas con pesos moleculares entre los 20 y 40 kDa, 6 entre los 40 y 50 kDa, 7 entre los 50 y 60 kDa, 19 cepas entre los 60 y 70 kDa, 29 entre los 70 y 100 kDa y 39 cepas entre los 100 y 145 kDa. Los análisis mediante PCR mostró que la colección presenta una gran diversidad de genes cry, observándose varios genes por cepa: 78 cepas presentaron el gen vip3, 82 el gen cry2, 45 el gen cry1 y 29 cepas los genes cry3 y cry7. Un total de 13 cepas no amplificaron con los iniciadores cry1, cry2, cry3-7, cry5, cry11cry12 y cry14. Se encontraron 43 perfiles genéticos diferentes, detectándose principalmente la combinación de genes cry1A con otros genes cry o vip. La caracterización genética de esta colección provee información importante para la selección de cepas de Bacillus thuringiensis que se evaluarán mediante bioensayos contra Hypothenemus hampei u otras plagas de importancia económica.

 Bacillus thuringiensis crystals cry genes delta -endotoxins Hypothenemus hampei coffee Bacillus thuringiensis cristales genes cry delta -endotoxinas Hypothenemus hampei café Apoyolo C.I Drif L Vassal J.M Debarjac H Bossy J.P Leclant F Frutos R Isolation of multiple subspecies of Bacillus thuringiensis from a population of the European sunflower moth, Homoeosoma nebulella Appl. Environ. Microbiol 1995 61 Arrieta G Caracterización molecular de las delta -endotoxinas de una colección de Bacillus thuringiensis aislada a partir de ecosistemas silvestres y agrícolas de Costa Rica Caracterización molecular de las delta -endotoxinas de una colección de Bacillus thuringiensis aislada a partir de ecosistemas silvestres y agrícolas de Costa Rica 2003 Bechtel D. B Bulla L.A Electron microscopic study of sporulation and parasporal formation in Bacillus thuringiensis J. Bacteriol 1976 127 Ben-Dov E Zaritsky A Dahan E Barak Z Sinai R Manasherob R Khamraev A Troitskaya E Dubitsky A Berezina N Margalith Y Extended screening by PCR for seven cry-group genes from field-collected strains of Bacillus thuringiensis Appl. Environ. Microbiol 1997 63 Bernhard K Studies on the delta-endotoxin of Bacillus thuringiensis var. Tenebrionis FEMS Microbiol. Lett 1986 33 Bernhard K Jarret P Meadows M Butt J Ellis D.J Roberts G.M Pauli S Rogers P Burges H.D Natural isolates of Bacillus thuringiensis: worldwide distribution, characterization and activity against insect pest J. Invertebr. Pathol 1997 70 Brun L.O Marcillaud C Gaudichon V Suckling D.M Endosulfan resistance in Hypothenemus hampei (Coleoptera: Scolytidae) in New Caledonia J. Econ. Entomol 1989 82 Bravo A Sarabia S López L Ontiveros H Abarca C Ortiz A Ortiz M Lina L Villalobos J Peña G Noez V Soberón M Quintero R Characterization of cry genes in a Mexican Bacillus thuringiensis strain collection Appl. Environ. Microbiol 1998 64 Carozzi N. B Kramer V.C Warren G. W Evola S Koziel M.G Prediction of insecticidal activity of Bacillus thuringiensis strains by polymerase chain reaction product profiles Appl. Environ. Microbiol 1991 57 Chen W Kuo T A simple and rapid method for the preparation of gram-negative bacterial genomic DNA Nucleic Acid Research 1993 21 Estruch J.J Warren G.W Mullins M.A Nye G.J Craig J.A Koziel M.G Vip3A, a novel Bacillus thuringiensis vegetative insecticidal protein with a wide spectum of activities against lepidopteran insects Proc. Natl. Acad. Sci 1996 93 Ferrandis M. D Juárez-Pérez V. M Frutos R Bel Y Ferré J Distribution of cry1, cryII and cryV genes within Bacillus thuringiensis isolates from Spain Syst. Appl. Microbiol 1999 22 Gustafson M.E Clayton R.A Lavrik P.B Jonhson G.V Leimgruber R.M Sims S.R Bartnicki D.E Large-scale production and characterization of Bacillus thuringiensis subsp. tenebrionis insecticidal protein from Escherichia coli Appl. Microbiol. Biotech 1997 47 Hatanaka T Choi Y Kusano T Sano H Transgenic plants of coffee Coffea arabica from embryogenic callus via Agrobacterium tumefaciens-mediated transformation Plant Cell Reports 1999 19 Kim H.S Lee D.W Woo S.D Yu Y.M Kang S.K Distribution, serological identification, and PCR analysis of Bacillus thuringiensis isolated from soils of Korea Curr. Microbiol 1998 37 Le Pelley R.H Pest of coffee Pest of coffee 1968 Longman Méndez-López I Basurto-Ríos R Ibarra J Bacillus thuringiensis serovar israelensis is highly toxic to the coffee berry borer, Hypothenemus hampei Ferr. (Coleoptera: Scolytidae) FEMS Microbiol. Lett 2003 11131 Porcar M Juárez-Pérez V PCR-based identification of Bacillus thuringiensis pesticidal crystal genes FEMS Microbiol. Rev 2003 26 Samsonov P Padrón R.I Pardo C Cabrera J De al Riva G.A Bacillus thuringiensis from biodiversity to biotechnology J. Ind. Microbiol. Biotech 1997 19 Sanchis V Lereclus D Menou G Chaufaux J Lecadet M.M Multiplicity of delta -endotoxin genes with different specificities in Bacillus thuringiensis aizawai Mol. Microbiol 1988 2 Schnepf H.E Crickmore N Van Rie N Dereclus J Baum J Feitelson J Zeigler D.R Dean D.H Bacillus thuringiensis and its pesticidal crystal proteins Microbiol. Mol. Biol. Rev 1998 62 Travers R. S Martin P.A.W Reichelderfer C.F Selective process for efficient isolation of soil Bacillus spp Appl. Environ. Microbiol 1987 53
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300037 Expression of the rice hoja blanca virus (RHBV) non-structural protein 3 (NS3) in Escherichia coli and its in situ localization in RHBV-infected rice tissues Muñoz Miguel Bolaños Isela Arrieta-Espinoza Griselda Espinoza Ana M ,Universidad de Costa Rica ,Universidad de Costa Rica 09 2004 2004 52 765 775

The non-structural NS3 protein gene from the rice hoja blanca virus (RHBV) was fused to the glutathione- S-transferase carboxilic end and expressed in Escherichia coli strain JM83. Large quantities of fusion protein were produced in insoluble form. The fusion protein was fractionated in SDS-PAGE and purified by electroelution, polyclonal antibodies were raised in rabbit and the antiserum was absorbed with bacterial crude extract. A band of similar size as that of NS3 protein was observed in Western blots using extracts from RHBV-infected rice plants. Immunoelectron microscopy with colloidal gold-labeled antibodies against NS3 protein and the viral nucleocapsid protein revealed in situ accumulation of NS3 protein in the cytoplasm but not in the viral inclusion bodies, vacuoles or chloroplasts of RHBV-infected plants, following the same pattern of distribution as the RHBV nucleocapsid protein. Rev. Biol. Trop. 52(3): 765-775. Epub 2004 Dic 15.

El gen que codifica por la proteína no estructural NS3 del virus de la hoja blanca de arroz (RHBV) se fusionó al extremo carboxilo del gen de la glutationa-S-transferasa y se expresó en la cepa JM83 de Escherichia coli. Se obtuvieron altas concentraciones de la proteína de fusion (GST-NS3) en forma insoluble. La proteína de fusión se fraccionó en geles de SDS-PAGE, se purificó por electroelución, y se utilizó para producir anticuerpos policlonales en conejo . El antisuero producido se absorbió con extractos crudos de E. coli. Extractos crudos de plantas de arroz sanas e infectadas con el RHBV se evaluaron por Western blots detectándose una banda de peso molecular similar al estimado para la proteína NS3 (23KDa) en las plantas infectadas con el virus. Los tejidos provenientes de plantas infectadas con el RHBV se analizaron por medio de microscopia inmunoelectrónica con oro colloidal marcado con anticuerpos contra la proteína NS3 y la nucleoproteína viral N. Se observó una acumulación in situ de la proteína NS3 en el citoplasma, pero no se detectó en los cuerpos de inclusion, vacuolas o cloroplastos. Se demostró que la proteína NS3 sigue el mismo patron de distribución que el de la nucleoproteína viral N del RHBV.

 Rice hoja blanca virus RHBV NS3 polyclonal antibodies immunoelectron microscopy Virus hoja blanca arroz RHBV NS3 anticuerpos policlonales inmunoelectro microscopía Amann E Brosius J Ptashne M Vectors bearing a hybrid trp-lac promoter useful for regulated expression of cloned genes in Escherichia coli Gene 1983 25 Citovsky V Zambrisky P Transport of nucleic acids through membrane channels: snaking through small holes Ann. Rev. Microbiol 1995 47 de Miranda J Hernández M Hull R Espinoza A Sequence analysis of rice hoja blanca virus RNA-3 J. Gen. Virol 1994 75 de Miranda J Hull R Espinoza A.M Sequence of the PV2 gene of rice hoja blanca tenuivirus RNA-2 Virus Genes 1995 10 de Miranda J Muñoz M Wu R Espinoza A.M Sequence of the Rice hoja blanca tenuivirus RNA-2 Virus Genes 1996 12 Dean P Affinity chromatography: a practical approach Affinity chromatography: a practical approach 1991 Oxford IRL Espinoza A.M Hernández M Pereira R Falk B Medina V In situ immunogold labeling analysis of the Rice hoja blanca virus nucleoprotein and major non-capsid protein Virology 1992 191 Espinoza A.M Pereira R Macaya-Lizano A Hernández M Goulden M Rivera C Comparative light and electron microscopic analyses of tenuivirus major non-capsid protein (NCP) inclusion bodies in infected plants and of the NCP in vitro Virology 1993 195 Huiet L Klaassen V Tsai J Falk B Nucleotide sequence and RNA hybridization analyses reveal an ambisense coding strategy for maize stripe virus RNA3 Virology 1991 182 Jennings P Estimating yield loss in rice caused by hoja blanca Phytopathology 1963 53 Kakutani T Hayano Y Hayashi T Minobe Y Ambisense segment 3 of rice stripe virus: the first instance of a virus containing two ambisense segments J. Gen. Virol 1991 72 Laemmli U Cleavage of structural proteins during the assembly of the head of the bacteriophage T4 Nature 1970 227 Lucas W Gilbertson R Plasmodesmata in relation to viral movement within leaf tissues Annu. Rev. Phytopathol 1994 32 Marston F Glover D.M The Purification of eukaryotic polypeptides expressed in Escherichia coli DNA cloning: a Practical approach. Volume III DNA cloning: a Practical approach. Volume III 1987 Oxford IRL Nault L Ammar E Leafhopper and planthopper transmission of plant viruses Annual Review of Entomology 1989 34 Nguyen M Ramírez B Goldbach R Haenni A Characterization of the in vitro activity of the RNA-dependent RNA polymerase associated with the ribonucleoproteins of rice hoja blanca tenuivirus J. Gen. Virol 1997 71 Ramírez B Macaya G Calvert L Haenni A Rice hoja blanca virus genome. Characterization and expression in vitro J. Gen. Virol 1992 73 Ramírez B Haenni A Molecular biology of tenuiviruses, a remarkable group of plant virases J. Gen. Virol 1994 75 Ramírez B Lozano I Constanino L Haenni A Calvert L Complete nucleotide sequence and coding strategy of rice hoja blanca virus RNA-4 J. Gen. Virol 1993 74 Sambrook J Fritsch E Maniatis T Molecular cloning: a laboratory manual Molecular cloning: a laboratory manual 1989 3 Cold Spring Harbor Laboratory Schoumacher F Erny C Verna A Godefroy-Colburn T Stussi-Garaud C Nucleic acid binding properties of the alfalfa mosaic virus protein produced in yeast Virology 1992 188 Smith D Corcoran L Ausubel F Brent R Kingston R Moore D Seidman J Smith J Struhl K Expression and purification of glutathione-S-transferase fusio N-proteins Current Protocols in Molecular Biology, vol II Current Protocols in Molecular Biology, vol II 1992 6th ^eNew York John Wiley Smith D Daver K Board P Tiu W García E Mitchell G Mr 26000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite Glutatione S-transferase Proc. Natl. Acad. Sci., U.S.A 1986 38 Smith D Johnson K Single step purification of polypeptides expressed in Escherichia coli as fusions with Glutatione S-transferase Gene 1988 67 Thomas C Maule A Identification of the cauli-flower mosaic virus movement protein RNA-binding domains Virology 1995 206 Toriyama S Takahashi M Sano Y Shimizu T Nucleotide sequence of RNA-1, the largest genomic segment of rice stripe virus, the prototype of the tenuiviruses J. Gen. Virol 1994 75 Volkin D Klibanov A Creighton T.E Minimizing protein inactivation Protein function: a practical approach Protein function: a practical approach 1989 Oxford IRL, Oxford University
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300038 Phylogenetic position of the yeast-like symbiotes of Tagosodes orizicolus (Homoptera: Delphacidae) based on 18S ribosomal DNA partial sequences Xet-Mull Ana M Quesada Tania Espinoza Ana M ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 777 785

Tagosodes orizicolus Muir (Homoptera: Delphacidae), the endemic delphacid species of tropical America carries yeast-like symbiotes (YLS) in the abdominal fat bodies and the ovarial tissues, like other rice planthoppers of Asia. These YLS are obligate symbiotes, which are transmitted transovarially, and maintain a mutualistic relationship with the insect host. This characteristic has made in vitro culture and classification of YLS rather difficult using conventional methods. Nevertheless, microorganisms of similar characteristics have been successfully classified by using molecular taxonomy. In the present work, the YLS of Tagosodes orizicolus(YLSTo) were purified on Percoll® gradients, and specific segments of 18S rDNA were amplified by PCR, cloned and sequenced. Sequences were aligned by means of the CLUSTAL V (DNASTAR) program; phylogenetic trees were constructed with the Phylogeny Inference Package (PHYLIP), showing that YLSTo belong to the fungi class Pyrenomycetes, phylum Ascomycota. Similarities between 98% and 100% were observed among YLS of the rice delphacids Tagosodes orizicolus, Nilaparvata lugens, Laodelphax striatellus and Sogatella furcifera, and between 89.8% and 90.8% when comparing the above to YLS of the aphid Hamiltonaphis styraci. These comparisons revealed that delphacid YLS are a highly conserved monophyletic group within the Pyrenomycetes and are closely related to Hypomyces chrysospermus. Rev. Biol. Trop. 52(3): 777-785. Epub 2004 Dic 15.

Tagosodes orizicolus Muir (Homoptera: Delphacidae) es una especie endémica de América tropical que al igual que otros saltahojas de Asia, tiene simbiontes levaduriformes (YLS, por sus siglas en Inglés) en los cuerpos grasos del abdomen y en los tejidos de los ovarios. Los YLS son simbiontes obligados que se transmiten transovarialmente y que mantienen relaciones mutualística con el insecto hospedero. Esta característica ha hecho muy difícil su cultivo in vitro y por ende su clasificación utilizando métodos convencionales. Sin embargo, otros microorganismos de características similares se han clasificado con éxito utilizando taxonomía molecular. El presente trabajo tiene como objetivo caracterizar los YLS del delfácido Tagosodes orizicolus (YLSTo). Para ello se purificaron los YLSTo en gradientes de Percoll® y el ADN extraído se amplificó por PCR utilizando iniciadores específicos para secuencias parciales del ADN ribosomal 18S. Dichos fragmentos se clonaron y secuenciaron posteriormente. Las secuencias se alinearon mediante el programa CLUSTAL V DNASTAR) y se construyeron árboles filogenéticos con el programa Phylogeny Inference Package (PHYLIP). Se encontró que los YLSTo pertenecen a la clase de hongos Pyrenomycetes, phylum Ascomycota. Se observaron índices de similaridad entre 98% y 100% entre los YLS de Tagosodes orizicolus, Nilaparvata lugens, Laodelphax striatellus and Sogatella furcifera (todos delfácidos de arroz), e índices de similaridad entre 89.8% y 90.8% al compararse con los YLS del áfido Hamiltonaphis styraci. Estas comparaciones revelaron que los YLS de los delfácidos constituyen un grupo monofilético altamente conservado dentro de los Pyrenomycetes y que se relacionan cercanamente con Hypomyces chrysospermus.

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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300039 Un método de transformación genética de maíz para conferirle resistencia ulterior a enfermedades virales Valdez Marta Madriz Kenneth Ramírez Pilar ,Universidad de Costa Rica San José Costa Rica ,Universidad de Costa Rica San José Costa Rica 09 2004 2004 52 787 793

A method for genetic transformation of maize for resistance to viral diseases. A system for the genetic transformation of maize was developed for two Costa Rican varieties: CR-7 and Diamantes 8843, that can allow the subsequent transfer of viral-derived genes in order to confer resistance to the disease caused by maize rayado fino virus (MRFV). The method is based on particle bombardment of organogenic calli derived from shoot tips. On the other hand, the molecular construction pRFcp-bar, containing the coat protein gene of MRFV and the marker gene bar, was elaborated. For the visual selection of the transformed material was used also the plasmid pDM803 that contains the reporter gene uidA (GUS).The results indicate that devices evaluated: the PIG (" Particle Inflow Gun ") and the Bio-Rad &trade; are both enough efficient to transfer foreign genes to the genome of the maize. Rev. Biol. Trop. 52(3): 787-793. Epub 2004 Dic 15.

Se desarrolló un sistema de transformación genética para dos variedades costarricenses de maíz: CR-7 y Diamantes 8843, que permita la transferencia ulterior de genes de origen viral a su genoma, y conferirles resistencia a la enfermedad ocasionada por el virus del rayado fino del maíz (MRFV). El método se basa en el bombardeo de microproyectiles en callos organogénicos derivados de ápices de jóvenes vitrogerminaciones. Por otro lado, se elaboró la construcción molecular pRFcp-bar que contiene el gen de la cubierta proteica del MRFV y el gen marcador bar. Para la selección visual del material transformado, se utilizo también el plásmido pDM803 que contiene el gen reportero uidA (GUS). Los resultados indican que los dos aceleradores de partículas evaluados: el PIG ("Particle Inflow Gun") y el Bio-Rad&trade; son igualmente eficientes para transferir genes foráneos al genoma del maíz.

 Zea mays Biotechnology Genetic Transformation Biolistics maize rayado fino virus (MRFV) Zea mays Biotecnología Transformación Genética Biobalística virus del rayado fino del maíz (MRFV) Beachy R.N Loesch-Fries S Tumer N.E Coat protein-mediated resistance against virus infection Annu. Rev. Phytopathol 1990 28 Bevan MW Flavell R.B Chilton M.D Structure and transcription of the nopaline synthase gene region of the T-DNA Nucl. Ac. Res 1983 11 Christensen A.H Sharrock R.A Quail P.H Maize polyubiquitin genes: Structure, thermal perturbation of expression, transcript splicing, and promoter activity following transfer to protoplasts by electroporation Plant Mol. Biol 1992 18 Finner J Vain P Jones M.W McMullen M.D Development of the Particle Inflow Gun for AND delivery to plant cells Plant Cell Rep 1992 11 White maize: a traditional food grain in developing countries White maize: a traditional food grain in developing countries 1997 Fromm M.E Morrish F Armstrong C Williams R Thomas J Klein T.M Inheritance and expression of chimeric genes in the progeny of transgenic maize plants Bio Technol 1990 8 Gallagher S GUS protocols: Using the GUS gene as a reporter of gene expression GUS protocols: Using the GUS gene as a reporter of gene expression 1992 Academic Gámez R A new Leafhopper-borne virus of corn in Central America Plant Dis. Rep 1969 53 Gámez R Transmission of rayado fino virus of maize (Zea mays) by Dalbulus maidis Ann. Appl. Biol 1973 73 Gámez R Rayado Fino Virus disease of maize in the American tropics Trop. Pest Manage 1980 26 Gámez R Plum R.T Thresh J.M The ecology of maize rayado fino virus in the American tropics Plant Virus Epidemiology Plant Virus Epidemiology 1983 Oxford Blackwell Scientific Gloria C Broglie R Edward C Chua N-H Tissue specif and light-regulated expression of a pea nuclear gene encoding the small subunit of ribulose-1,5- bisphosphate carboxylase Eur. Mol. Biol. Org. J 1984 3 Gordon-Kamm W.J Spencer T.M Manganno M.L Adams T.R Daines R.J Willets N.G Rice T.B Mackey C.J Krueger R.W Kaush A.P Lamaux P.G Transformation of maize cells and regeneration of fertile transgenic plants Plant Cell 1990 2 Hammond R.W Ramirez P Molecular characterization of the genome of Maize Rayado Fino Virus, the Type member of the Genus Marafivirus Virol 2001 282 Jefferson R.A Assaying chimeric genes in plants: the GUS gene fusion system Plant Mol. Biol 1987 6 Kogel R Hammond R.W Ramirez P Incidence and geographic distribution of maize rayado fino virus (MRFV) Plant Dis 1996 80 Lomonossoff G.P Pathogen-derived resistance to plant viruses Annu. Rev. Phytopathol 1995 33 Madriz-Ordeñana K Molecular studies of the defence responses of maize (Zea mys L.) in interaction with Maize Rayado Fino Marafivirus (MRFV) Molecular studies of the defence responses of maize (Zea mys L.) in interaction with Maize Rayado Fino Marafivirus (MRFV) 1999 McElroy D Blowers A.D Jenes B Wu R Construction of expression vectors based on the rice actin 1(Act1) 5_region for use in monocot transformation Mol. Gen. Genet 1991 231 Murashige T Skoog F A revised medium for rapid growth and bioassays with tobacco tissue cultures Physiol. Plant 1962 15 O’Connor-Sánchez A Cabrera-Ponce J.L Valdez-Melara M Téllez-Rodríguez P Pons-Hernández J.L Herrera-Estrella L Transgenic maize plants of tropical and subtropical genotypes obtained from calluses containing organogenic and embryogenic-like structures derived from shoot tips Plant Cell Rep 2002 21 Rhodes C.A Pierce D.A Mettler J.L Mascarenhas D Detmer J.J Genetically transformed maize plants from protoplasts Science 1988 240 Sanford J.C Johnston S.A The concept of parasite- derived resistance: deriving resistance genes from the parasites own genome J. Theor. Biol 1985 115 Sanford J.C Klein T.M Wolf E.D Allen N Delivery of sustances into cells and tissues using a particle bombardment process Part. Sci. Technol 1987 5 Spencer T.M Gordon-Kamm W.J Daines R.J Lemaux P.G Bialaphos selection of stable transformants from maize cell cultures Theor. Appl. Genet 1990 79 Thomson C.J Nova N.R Tizzard R Crameri R Davis J.E Lauwerys M Botterman J Characterization of the herbicide resistance gene bar from Streptomyces hygroscopicus Eur. Mol. Biol. Org. J 1987 6 Valdez M Cabrera-Ponce J.L Sudhakar D Herrera-Estrella L Christou P Transgenic Central American, West African and Asian elite rice varieties resulting from particle bombardment of foreign DNA into mature seed-derived explants utilizing three different bombardment devices Ann. Bot 1998 82 Vasil I Thorpe T Plant cell and tissue culture Plant cell and tissue culture 1994 Kluwer Academics
S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300040 Genetic diversity of Costa Rican populations of the rice planthopper Tagosodes orizicolus (Homoptera: Delphacidae) Hernández Myriam Quesada Tania Muñoz Claudia Espinoza Ana M ,Universidad de Costa Rica Sabanilla de Montes de Oca San José Costa Rica ,Universidad de Costa Rica San Pedro San José Costa Rica 09 2004 2004 52 795 806

Tagosodes orizicolus (Homoptera: Delphacidae) is one of the main constraints of the rice production in the Neotropics. This planthopper produces severe damages as a phloem feeder, causes mechanical injury during oviposition and vectors the rice hoja blanca virus (RHBV). The main objective of this study was to determine the genetic diversity of T. orizicolus populations from three rice growing regions of Costa Rica, using RAPDs. Individuals from Guanacaste, Parrita, San Carlos and Cali-Colombia, as outgroup, were analyzed using the random primers. Phenetic relationships revealed that the Costa Rican populations were clearly separated from Cali-Colombia, sharing less than 25% similarity. Costa Rican populations were divided into two main branches separated at 30% similarity. The first branch included Guanacaste and San Carlos and the second displayed Parrita. In relation to similarity indexes within groups, the Guanacaste cluster showed the highest (over 50%) and Cali-Colombia was the most diverse (28%). The correspondence analysis confirmed the clusters of the phenogram and showed close interactions between the Parrita and San Carlos populations. The genetic separation observed could be the result of the geographic isolation among populations, but it could also be explained by the infection with the rickettsia Wolbachia pipientis. This bacterium causes cytoplasmic incompatibility in its host, which results in non-viable progeny when infected males mate with non-infected females, or when insects hosting different strains of Wolbachia mate. Then, a search for Wolbachia in previously described populations of T. orizicolus was initiated. The presence of the bacteria was analyzed by PCR with 16S rDNA-specific primers for Wolbachia. The PCR analyses revealed infections of 86% in the population of San Carlos, 96% in Guanacaste, 37% in Parrita and 100% in Cali-Colombia. Crosses between individuals of T. orizicolus from Parrita and Guanacaste were performed for testing cytoplasmic incompatibility. When infected males were crossed with non-infected females within the same population, a significant reduction in progeny number was obtained as well as when crosses between infected individuals belonging to different populations were performed. These experiments showed cytoplasmic incompatibility not only caused by the presence of Wolbachia within the population, but also by the presence of different strains of the bacteria between populations. Rev. Biol. Trop. 52(3): 795-806. Epub 2004 Dic 15.

Tagosodes orizicolus (Homoptera: Delphacidae) es uno de las principales plagas de arroz en el Neotrópico, ya que se alimenta de la savia del floema, realiza incisiones durante la oviposición que dañan los haces vasculares de las hojas y es el vector del virus de la hoja blanca del arroz (RHBV). El objetivo de esta investigación es determinar la diversidad genética de las poblaciones de T. orizicolus de las principales zonas arroceras del Costa Rica. Para ello se analizaron mediante RAPDs individuos de las población de Guanacaste, Parrita y San Carlos y como grupo externo Cali-Colombia. El fenograma mostró que los individuos agruparon de acuerdo a su localidad, observándose que las tres poblaciones costarricenses se separaron de la Colombiana, compartiendo menos del 25% de similaridad. Las poblaciones costarricenses se separaron en dos brazos principales a un 30% de similaridad: el primero incluyó Guanacaste y San Carlos, mientras que el segundo lo constituyó Parrita. El conglomerado de Guanacaste mostró un índice de similaridad del 50% entre individuos mientras que la población de Cali-Colombia fue la más diversa (28%). Finalmente, el análisis de correspondencia confirmó los conglomerados observados en el fenograma y mostró una interacción cercana entre las poblaciones de Parrita y San Carlos. La separación genética observada podría ser el resultado del aislamiento geográfico entre poblaciones pero también podría explicarse por la infección con la rickettsia Wolbachia pipientis. Esta bacteria causa incompatibilidad citoplasmática en sus hospederos, lo cual resulta en una progenie no viable en los cruces entre machos infectados con hembras no infectadas, o cuando ocurren cruces entre insectos infectados con diferentes cepas de Wolbachia. Otro objetivo de esta invsetigación fue determinar por PCR la presencia de Wolbachia en las poblaciones antes mencionadas, utilizando iniciadores específicos para el rADN 16S. Dicho análisis reveló infecciones del 86% en la población de San Carlos, un 96% en Guanacaste, un 37% en Parrita y un 100% en Cali-Colombia. Con el fin de determinar si se presenta incompatibilidad citoplasmática, se llevaron a cabo cruces entre individuos de T. orizicolus de Parrita y Guanacaste. Se observó una reducción significativa en la progenie en los cruces entre machos infectados y hembras no infectadas de una misma población, así como, en los cruces entre individuos infectados pertenecientes a poblaciones diferentes. Estos resultados mostraron incompatibilidad citoplasmática, no sólo causada por la presencia de Wolbachia, sino también por la presencia de diferentes cepas de la bacteria entre poblaciones de T. orizicolus.

 Tagosodes orizicolus delphacid genetic diversity Wolbachia RAPDs cytoplasmic incompatibility Tagosodes orizicolus delfácido diversitdad genética Wolbachia RAPDs incompatibilidad citoplasmática Bordenstein S.R O’Hara F.P Werren J.H Wolbachia-induced incompatibility precedes other hybrid incompatibilities in Nasonia Nature 2001 409 Boyle L O’Neill S Robertson M.H Karr T.L Interspecific and intraspecific horizontal transfer of Wolbachia in Drosophila Science 1993 260 Denno F.R Perfect J.T Denno F.R Perfect T.J Planthoppers as models for ecological study and effective pest management Planthoppers: Their ecology and management Planthoppers: Their ecology and management 1994 Chapman & Hall Espinoza A.M Xet-Mull A.M Mora R Sánchez E Morphologic characterization of yeast-like symbiotes of Tagosodes orizicolus (Homoptera: Delphacidae) by light and electron microscopy Rev. Biol. 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S0034-774420040003 Revista de Biología Tropical Rev. biol. trop 0034-7744 Universidad de Costa Rica S0034-77442004000300041 In vitro antiviral activity of Chamaecrista nictitans (Fabaceae )against herpes simplex virus: Biological characterization of mechanisms of action Herrero Uribe Libia Chaves Olarte Esteban Tamayo Castillo Giselle ,Universidad de Costa Rica ,Universidad de Costa Rica Costa Rica 09 2004 2004 52 807 816

We have previously identified a crude extract of the plant Chamaecrista nictitans (Fabaceae)with antiviral activity against herpes simplex virus.The main objectives of this research were to identify the step of the replication cycle of herpes simplex inhibited by the extract,and to attempt to characterize the chemical characteristics of this extract.The crude extract from Chamaecrista nictitans (Fabaceae)was extracted with a mixture of diclorometane/methanol,and further fractionated following a bioassay-guided protocol using a combination of preparative thin layer and column chromatography.Toxicity and bioassay experiments were carried out in monolayers of Vero cells.The antiviral activity of the extract was assessed by total inhibition of cytopathic effect after three-day incubation.The highest concentration of the extract which was not toxic to the cells was 200 mu g/ml. Western blot and immunofluorescence techniques were used to elucidate the antiviral mechanism of the extract by infecting Vero cells with the virus at different times and monitoring the synthesis of viral proteins.A 60 kDa protein was detected at 2 hr and 8 hr post-infection but no additional proteins were synthesized at later time intervals,and cytopathic effect was not observed after 24 hr.This result indicates that the extract acts at the intracellular level in order to inhibit late transcription.However,it does not inhibit transcription/translation of early viral proteins.These results were confirmed by immunofluorescence experiments.A strong fluorescent signal was observed in control cell monolayers at 24 hr post infection,accompanied with a clear cytopathic effect.In contrast,in the presence of acyclovir or the extract,cells showed very discrete immunofluorescence,characterized by a punctuated pattern, and no cytopathic effect was observed.Neutralization assays were performed using pre-incubation of virus with either specific herpes simplex-1 antiserum,200 mu g/ml of the extract or 20 mu g /ml of acyclovir.After 1 hr incubation,cells were infected and monitored for cytopathic effect.Only the virus treated with acyclovir showed viral activity,while no cytopathic effect was induced by samples of virus incubated with the extract.It is concluded that the extract inhibits both the attachment of the virus to the cell and the secondary transcription of the virus within the cells.Chemical characterization of the extract showed the presence of tannins.Rev.Biol.Trop.52(3):807-816. Epub 2004 Dic 15.

Previamente se había identificado un extracto crudo a partir de Chamaecrista nictitans (Fabaceae)con actividad antiviral contra el virus herpes simplex.Los objetivos de esta investigación fueron determinar el paso en el ciclo de replicación del herpes simplex inhibidos por el extracto y caracterizar la naturaleza química de dicho extracto.El extracto crudo de la planta se obtuvo con una mezcla de diclorometano/metanol y fraccionado,utilizando la guía de un bioensayo,mediante cromatografía preparativa de capa fina y cromatografía en columna.Los ensayos se llevaron a cabo en monocapas de células Vero.La actividad antiviral exhibida por el extracto fue determinada mediante la inhibición total del efecto citopático después de tres días de incubación.La concentración máxima de la fracción positiva que no presentó citotoxicidad fue 200 µg/ml.Se utilizaron técnicas inmunoquímicas y de inmunofluorescencia para elucidar el mecanismo antiviral ejercido por el extracto; con este propósito,se infectaron células Vero con el virus herpes simplex y se determinó la producción de proteínas virales a diferentes tiempos después de la infección.Se detectó la producción de una proteína de aproximadamente 60 kDa a las 2 hr y 8 hr luego de la infección;sin embargo no se detectó producción de ningún tipo de proteína tardía, hecho correlacionado con la ausencia de efecto citopático a las 24 hr.Este resultado indica que el extracto actúa intracelularmente siendo capaz de inhibir la transcripción secundaria.Sin embargo,el extracto permite la transcripción y traducción de proteínas tempranas.Estos resultados fueron confirmados mediante inmunofluorescencia.En células control no tratadas con el extracto,se observó una fuerte señal fluorescente acompañada de la aparición del efecto citopático característico 24 hr después de la infección con el virus herpes simplex.Por el contrario,células en presencia de acyclovir o del extracto desarrollaron un patrón muy discreto de inmunofluorescencia sin presencia de efecto citopático.Se realizaron adicionalmente ensayos de neutralización utilizando preincubaciones con un antisuero específico contra herpes simplex 1,200 µg/ml del extracto o 20 µg/ml de acyclovir.Solamente el virus tratado con acyclovir fue capaz de producir un efecto citopático,mientras que el extracto inhibió el virus y no se detectó efecto citopático. Se concluye que el extracto inhibe la adherencia inicial del virus a las células y los eventos de transcripción secundaria del virus.La caracterización química del extracto demostró la presencia de taninos en el mismo.

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