[Programa de detección del alelo APOE-E4 en adultos mayores mexicanos con deterioro cognitivo].

INTRODUCTION: In Mexico, the prevalence of neurocognitive disorders (NCDs) has increased in parallel with the increase in life expectancy. The E4 allele of the gene that encodes apolipoprotein E (APOE) is the main genetic risk factor for cognitive impairment. OBJECTIVE: To replicate the association of APOE-E4 allele with neurocognitive impairment in a Mexican population, as well as to implement a genetic risk-detection program with the APOE-E4 allele. METHOD: A program was structured for the detection of APOE-E4 allele risk in different recruiting centers from the central zone of the Mexican Republic, with three stages: recruitment and selection of candidates for the detection of the risk-allele, genetic risk analysis and delivery of results. RESULTS: In the genetic-association study to replicate the association with neurocognitive disorders by means of multivariate logistic models, the APOE-E4 allele increased the risk for cognitive impairment in the Mexican populations by approximately 6 % (OR: 5.83, p = 0.0025). In addition, 367 genetic risk results were delivered. CONCLUSIONS: The present program is the first one to be implemented in Mexico with the purpose to inform on a genetic risk factor for neurocognitive disorders in several centers of the country.

INTRODUCCIÓN: En México, la prevalencia de los trastornos neurocognitivos (TNC) han aumentado a la par del incremento en la esperanza de vida. El alelo E4 del gen que codifica la apolipoproteína E (APOE) es el principal factor de riesgo genético para deterioro neurocognitivo. OBJETIVO: Reproducir la asociación en población mexicana entre APOE-E4 y el deterioro neurocognitivo, así como implementar un programa de detección de riesgo genético con el alelo APOE-E4. MÉTODO: Se estructuró un programa de detección de riesgo basado en APO-EA en diferentes centros de reclutamiento en la zona centro de la República Mexicana, con tres etapas: reclutamiento y selección de los candidatos para la detección del alelo de riesgo, análisis del riesgo genético y entrega del resultado. RESULTADOS: El análisis de asociación genética para replicar la asociación con trastornos neurocognitivos mediante modelos logísticos multivariados mostró que el alelo E4 de APOE incrementó aproximadamente 6 % el riesgo en población mexicana (RM = 5.83, p = 0.0025). Se entregaron 367 resultados de riesgo genético. CONCLUSIONES: El presente programa es el primero en México implementado para dar a conocer un factor de riesgo genético para trastornos neurocognitivos en varios centros del país.

[Prevalence study of the genetic markers associated with slow progression of human inmunodefiency virus type 1 in the Galician population (Northwest of Spain)]. / Estudio de la prevalencia de marcadores genéticos asociados a la lenta progresión del virus de la inmunodeficiencia humana tipo 1 en la población gallega.

INTRODUCTION: The deletion in the CCR5 gene (CCR5Δ32), the HLA-B*27:05, and polymorphisms rs2395029 and rs9264942 have been associated with slower progression of HIV-1. METHODS: An analysis was performed on 408 patients on follow-up. The analysis of viral load, CD4+ Tlymphocytes and other clinical variables since the diagnosis of the infection were collected. RESULTS: The prevalence of the genetic markers rs9264942, CCR5wt/Δ32, rs2395029, HLA-B*27:05 was 17.9%, 11.5%, 7.6%, and 6.4%, respectively. Of all the patients, 354 were classified as progressors and 46 as long-term non-progressors (LTNPs). Except for the HLA-B*27:05 allele, other genetic markers were associated with slower progression: CCR5wt/Δ32 (P=.011) and SNPs rs2395029 and rs9264942 (P<.0001), as well as their association (P<.0001). CONCLUSION: The prevalence of the HLA-B*57:01 allele was higher than described nationally. No association could be found between the HLA-B*27:05 allele and the presence of slower disease progression.

[Isocitrate dehydrogenase type I mutation as a prognostic factor in glioblastoma and a literature review]. / Importancia de la mutación de la isocitrato deshidrogenasa tipo I como factor pronóstico en pacientes con glioblastomas y revisión de la literatura.

OBJECTIVE: Treatment response and prognosis in glioblastoma (GBM) tumours can differ among patients, highlighting the growing relevance of genetic biomarkers to differentiate glioblastoma sub-types. The biomarker isocitrate dehydrogenase (IDH1) is currently receiving considerable attention. The objective of this work was to analyse the clinical and prognostic differences between glioblastomas with and without the IDH1 mutation. METHODS: A retrospective study was performed on patients with GBM who underwent surgery between 2007 and 2012. The inclusion criteria were: patient age between 18-85 years who underwent surgery for the first time with complete macroscopic resection, complete adjuvant treatment with chemotherapy and radiotherapy, and a Karnofsky performance score>70. RESULTS: A total of 61 patients (36 males/25 famales) were included and with a mean age of 62.3 years. An IDH1mutation was found in 14 patients (23%). Median survival in patients with the IDH1 mutation (IDH1-m) was 23.6 months compared with 11.9 months in those with the wild type IDH1 (IDH1-wt) (P=.028). Disease onset in IDH1-m patients tended to be at a younger age, 58.7 vs. 63.4 years, but this difference was not statistically significant. CONCLUSION: Glioblastomas with IDH1-m should be considered a different entity from the IDH1-wt, as their natural history and prognosis differ. In the near future we should be classified glioblastomas based on the presence of the IDH1 mutation.

[The value of genetics in the era of hepatitis C triple therapy]. / Valor de la genética en la era de la terapia triple frente al virus de la hepatitis C.

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients.

Absence of Reliable Screening Methods That Prove the Use of Gene Doping in Sports / Ausencia de métodos de tamizaje fiables que demuestren el uso del dopaje genético en el deporte / Falta de métodos de triagem confiáveis para provar o uso de doping genético no esporte

Abstract: Sport raises the level of human physical activity within the limits of genetic traits. The results of gene therapy have attracted some to think of using its technologies to create an "indomitable athlete." World Anti-Doping Agency (WADA) applies uncertain genetic testing procedures to establish cases of this type of doping. Yet, if the results of these procedures are doubtful, then doubt must be interpreted in favor of the athlete concerned.

Resumen: El deporte eleva el nivel de actividad física humana dentro de los límites de los rasgos genéticos. Los resultados de la terapia génica han atraído a algunos a pensar en utilizar sus tecnologías para crear un 'atleta indomable'. La Agencia Mundial Antidopaje (AMA) aplica procedimientos de pruebas genéticas inciertos para establecer casos de este tipo de dopaje. Sin embargo, si los resultados de estos procedimientos son dudosos, entonces la duda debe interpretarse a favor del atleta en cuestión.

Resumo: O esporte eleva o nível da atividade física humana dentro dos limites dos traços genéticos. Os resultados da terapia genética têm atraído alguns a pensar em usar suas tecnologias para criar um "atleta indomável". A Agência Mundial Antidoping (WADA) aplica procedimentos incertos de testes genéticos para estabelecer casos deste tipo de dopagem. Entretanto, se os resultados desses procedimentos forem incertos, então a incerteza deve ser interpretada em favor do atleta em questão.

La evidencia científica de las consecuencias de la modernidad / Scientific evidence of the consequences of modernity

Resumen La prevalencia de diabetes tipo 2 (DT2) en México es del 14.4%. La enfermedad se caracteriza por un estado de hiperglucemia e inflamación crónica secundaria a la resistencia y la secreción inadecuada de insulina. Dentro de sus factores de riesgo destacan la obesidad, el sedentarismo, las dietas hipercalóricas y las variantes genéticas. Durante décadas, diferentes grupos de investigación básica y aplicada han trabajado de forma interdisciplinaria para ofrecer evidencia científica que ha ayudado a entender los mecanismos implicados en la fisiopatología de la DT2 en pacientes mexicanos. Sin embargo, hoy en día la urgencia de conseguir mejores propuestas de prevención y manejo del paciente con DT2 hace necesario el uso de la medicina traslacional, que integra el conocimiento científico con el uso de tecnologías innovadoras para brindar una atención integral. El presente documento describe de forma concisa y con un enfoque traslacional las implicaciones de la interacción de factores de riesgo ambientales y genéticos en el desarrollo de obesidad infantil y DT2 en México.

Abstract The prevalence of type 2 diabetes (T2D) in Mexico is 14.4%. This disease is characterized by a state of hyperglycemia and chronic inflammation secondary to inadequate insulin secretion and its resistance. Among its risk factors for metabolic diseases development, the interaction between obesity, sedentary lifestyle, hypercaloric diets and genetic variants play an important role. For decades, different basic and applied research groups have worked in an interdisciplinary way to provide scientific evidence that has helped to understand the mechanisms involved in the pathophysiology of T2D in Mexicans. However, today the urgency of the advance and better proposals for prevention and management of patients with T2D makes it necessary to use translational medicine, which integrates scientific knowledge with the use of innovative technologies to provide comprehensive health care. In this sense, the present document concisely describes, with a translational approach, the implications of the interaction of environmental and genetic risk factors in the development of childhood obesity and T2D in Mexico.

Analysis of the genetic diversity of Dragon fruit based on ISSR markers in Colombia

Abstract Selenicereus megalanthus H. is a tropical fruit belonging to the family Cactaceae, is rich in essential nutrients, antioxidants and bioactive components. It presents wide variability in different characteristics and a great demand in the market; however, genetic studies in Colombia are scarce. The main of this study was to characterize the genetic diversity of 76 yellow pitahaya genotypes with eight ISSR markers. Genetic parameters expected average heterozygosity (He), percentage of polymorphic loci, genetic distances and Fst were estimated with TFPGA. The analysis of the population genetic structure was carried out with the STRUCTURE 2.3.4. As a result, 225 alleles were generated and the number of polymorphic loci ranged 85 (CT, AG) to 90 (GT). High genetic diversity was found, with an average value of heterozygosity was 0.34 with a genetic differentiation coefficient (Fst) of 0.26, indicating that there was a great genetic diversity, similar values than those reported in other studies of pitahaya genetic diversity in Colombia. The 76 genotypes were grouped into K=3 according to geographic location, however, in some groups a mixture of individuals from different origins was observed. The analysis of molecular variance (AMOVA) showed higher variation (75%) within groups than among groups (25%). These results provide information that can be used to develop conservation strategies for dragon fruit and breeding programs to obtain more productive pitahaya genotypes with superior quality, high yield and with resistance to biotic and abiotic factors.

Resumo Selenicereus megalanthus H. é uma fruta tropical pertencente à família Cactaceae, rica em nutrientes essenciais, antioxidantes e componentes bioativos. Apresenta grande variabilidade em diferentes características e uma grande demanda no mercado; no entanto, os estudos genéticos na Colômbia são escassos. O principal deste estudo foi caracterizar a diversidade genética de 76 genótipos de pitahaya amarela com oito marcadores ISSR. Parâmetros genéticos esperados de heterozigosidade média (He), porcentagem de locos polimórficos, distâncias genéticas e Fst foram estimados com TFPGA. A análise da estrutura genética da população foi realizada com a ESTRUTURA 2.3.4. Como resultado, 225 alelos foram gerados e o número de loci polimórficos variou de 85 (CT, AG) a 90 (GT). Foi encontrada alta diversidade genética, com um valor médio de heterozigosidade de 0,34 com coeficiente de diferenciação genética (Fst) de 0,26, indicando que havia uma grande diversidade genética, valores semelhantes aos relatados em outros estudos de diversidade genética de pitahaya na Colômbia. Os 76 genótipos foram agrupados em K = 3 de acordo com a localização geográfica, porém, em alguns grupos foi observada uma mistura de indivíduos de diferentes origens. A análise de variância molecular (AMOVA) mostrou maior variação (75%) dentro dos grupos do que entre os grupos (25%). Esses resultados fornecem informações que podem ser utilizadas para desenvolver estratégias de conservação da fruta do dragão e programas de melhoramento para a obtenção de genótipos de pitahaya mais produtivos, com qualidade superior, alto rendimento e com resistência a fatores bióticos e abióticos.

Frequência alélica e potencial regulatório de polimorfismosno gene NELL1 em uma população da Bahia ­ Brasil / Allele frequency and regulatory potential of polimorphisms in NELL1 gene in a population of Bahia ­ Brazil

Introdução: o gene NELL1 codifica a proteína semelhante ao fator de crescimento epidérmico (do inglês Epidermal Growth factor (EGF)-like). GWASs e estudos de associação com genes candidatos têm sido utilizados para estabelecer a conexão entre polimorfismos de nucleotídeo único (SNP) no NELL1 e diversas doenças. Objetivo: descrever a frequência alélica e o potencial regulatório dos polimorfismos do gene NELL1, estudados em uma população de Salvador (Bahia, Brasil) e descrever a frequência desses polimorfismos e a associação com diversas doenças, em populações africana, ameríndia, asiática e europeia. Metodologia: 1094 participantes foram recrutados através do Programa de Controle da Asma e da Rinite Alérgica no Estado da Bahia (ProAR). Os indivíduos tiveram o DNA genômico extraído e genotipado, utilizando-se a plataforma Illumina. Os SNP foram consultados através da plataforma SeattleSec Annotation. As bases de dados NCBI, RegulomeDB e Haploview 4.2 foram utilizadas para as análises. Resultados: foram analisados 346 SNPs do gene NELL1. Desses, 53 SNPs tiveram o MAF variando entre 50% e 40% e função intrônica. Os SNPs rs10833465 (alelo A), rs908944 (alelo C), rs1516766 (alelo A), rs10766739 (alelo G) e rs11025878 (alelo G) apresentam uma pontuação de 3, de acordo com o banco do RegulomeDB. O SNP rs7117671, com pontuação 2b, pode ter impacto regulatório e funcional. 101 SNPs apresentaram o MAF entre 39% e 20%. Dos polimorfismos menos frequentes nessa população, 192 apresentaram um MAF entre 19% e 2%. Discussão: alguns SNPs, com diferentes frequências, apresentaram alta probabilidade de impacto funcional. Foram encontrados, na literatura, estudos de associação dos SNPs e osteoporose, doenças metabólicas, condições inflamatórias, doenças neuropsiquiátricas e tumores malignos. Conclusão: ospolimorfismos do gene NELL1 estudados apresentaram diferentes frequências na população desse estudo e tiveram seus alelos associados a doenças em diferentes populações. Sugere-se que sejam realizados mais estudos.

Introduction: the NELL1 gene encodes the epidermal growth factor (EGF)-like protein. GWASs and association studies with candidate genes have been used to establish the connection between single nucleotide polymorphisms (SNP) in NELL1 and various diseases. Objective: to describe the allele frequency and regulatory potential of NELL1 gene polymorphisms studied in a population from Salvador, Bahia, Brazil; and to describe the frequency of these polymorphisms, and the association with various diseases, in African, Amerindian, Asian and European populations. Methodology: one thousand and ninety-four (1094) participants were recruited through the Program for the Control of Asthma and Allergic Rhinitis in the State of Bahia (ProAR). Individuals had their genomic DNA extracted and genotyped using the Illumina platform. The SNPs were consulted through the SeattleSec Annotation platform. The NCBI, RegulomeDB and Haploview 4.2 databases were used for the analyses. Results: four hundred and seventy-three (346) NELL1 gene SNPs were analyzed. Of these, 53 SNPs had MAF ranging between 50% and 40% and intronic function. The SNPs rs10833465 (A allele), rs908944 (C allele), rs1516766 (A allele), rs10766739 (G allele) and rs11025878 (G allele) showed a score of 3, according to the RegulomeDB database. SNP rs7117671, with score 2b, may have regulatory and functional impact. One hundred and eighteen (101) SNPs presented MAF between 39% and 20%. Of the less frequent polymorphisms in this population, 192 had a MAF between 19% and 2%. Discussion: some SNPs, with different frequencies, presented a high probability of functional impact. Studies on the association of SNPs and osteoporosis, metabolic diseases, inflammatory conditions, neuropsychiatric diseases and malignant tumors were found in the literature. Conclusion: the NELL1 gene polymorphisms studied showed different frequencies in the population of this study and had their alleles associated with diseases in different populations. It is suggested that further studies be carried out.

Analysis of the genetic diversity of Dragon fruit based on ISSR markers in Colombia / Análise da diversidade genética da fruta do dragão com base em marcadores ISSR na Colômbia

Selenicereus megalanthus H. is a tropical fruit belonging to the family Cactaceae, is rich in essential nutrients, antioxidants and bioactive components. It presents wide variability in different characteristics and a great demand in the market; however, genetic studies in Colombia are scarce. The main of this study was to characterize the genetic diversity of 76 yellow pitahaya genotypes with eight ISSR markers. Genetic parameters expected average heterozygosity (He), percentage of polymorphic loci, genetic distances and Fst were estimated with TFPGA. The analysis of the population genetic structure was carried out with the STRUCTURE 2.3.4. As a result, 225 alleles were generated and the number of polymorphic loci ranged 85 (CT, AG) to 90 (GT). High genetic diversity was found, with an average value of heterozygosity was 0.34 with a genetic differentiation coefficient (Fst) of 0.26, indicating that there was a great genetic diversity, similar values than those reported in other studies of pitahaya genetic diversity in Colombia. The 76 genotypes were grouped into K=3 according to geographic location, however, in some groups a mixture of individuals from different origins was observed. The analysis of molecular variance (AMOVA) showed higher variation (75%) within groups than among groups (25%). These results provide information that can be used to develop conservation strategies for dragon fruit and breeding programs to obtain more productive pitahaya genotypes with superior quality, high yield and with resistance to biotic and abiotic factors.

Selenicereus megalanthus H. é uma fruta tropical pertencente à família Cactaceae, rica em nutrientes essenciais, antioxidantes e componentes bioativos. Apresenta grande variabilidade em diferentes características e uma grande demanda no mercado; no entanto, os estudos genéticos na Colômbia são escassos. O principal deste estudo foi caracterizar a diversidade genética de 76 genótipos de pitahaya amarela com oito marcadores ISSR. Parâmetros genéticos esperados de heterozigosidade média (He), porcentagem de locos polimórficos, distâncias genéticas e Fst foram estimados com TFPGA. A análise da estrutura genética da população foi realizada com a ESTRUTURA 2.3.4. Como resultado, 225 alelos foram gerados e o número de loci polimórficos variou de 85 (CT, AG) a 90 (GT). Foi encontrada alta diversidade genética, com um valor médio de heterozigosidade de 0,34 com coeficiente de diferenciação genética (Fst) de 0,26, indicando que havia uma grande diversidade genética, valores semelhantes aos relatados em outros estudos de diversidade genética de pitahaya na Colômbia. Os 76 genótipos foram agrupados em K = 3 de acordo com a localização geográfica, porém, em alguns grupos foi observada uma mistura de indivíduos de diferentes origens. A análise de variância molecular (AMOVA) mostrou maior variação (75%) dentro dos grupos do que entre os grupos (25%). Esses resultados fornecem informações que podem ser utilizadas para desenvolver estratégias de conservação da fruta do dragão e programas de melhoramento para a obtenção de genótipos de pitahaya mais produtivos, com qualidade superior, alto rendimento e com resistência a fatores bióticos e abióticos.

Behavior of the Genetic Markers at Screening during the First Trimester of Pregnancy in Euploid Fetuses / Comportamento dos marcadores genéticos na triagem durante o primeiro trimestre de gravidez em fetos euploides

Abstract Objective This study aims to describe the behavior of chromosomopathy screenings in euploid fetuses. Methods This is a prospective descriptive study with 566 patients at 11 to 14 weeks of gestation. The associations between ultrasound scans and serological variables were studied. For the quantitative variables we used the Spearman test; for the qualitative with quantitative variables the of Mann-Whitney U-test; and for qualitative variables, the X2 test was applied. Significance was set at p ≤ 0.05. Results We have found that gestational age has correlation with ductus venosus, nuchal translucency, free fraction of β subunit of human chorionic gonadotropin, pregnancy-associated plasma protein-A and placental growth factor; there is also a correlation between history of miscarriages and nasal bone. Furthermore, we correlated body mass index with nuchal translucency, free fraction of β subunit of human chorionic gonadotropin, and pregnancy-associated plasma protein-A. Maternal age was associated with free fraction of β subunit of human chorionic gonadotropin and pregnancy-associated plasma protein-A. Conclusion Our study demonstrates for the first time the behavior of the biochemical and ultrasonographic markers of chromosomopathy screenings during the first trimester in euploid fetuses in Colombia. Our information is consistent with international reference values. Moreover, we have shown the correlation of different variables with maternal characteristics to determine the variables that could help with development of a screening process during the first trimester with high detection rates.

Resumo Objetivo Este estudo tem como objetivo descrever o comportamento do rastreamento de cromossomopatias em fetos euploides. Métodos Trata-se de um estudo prospectivo descritivo com 566 pacientes, entre 11 e 14 semanas de gestação. A associação entre a ultrassonografia e as variáveis sorológicas foi estudada. Para as variáveis quantitativas foi utilizado o teste de Spearman; para as qualitativas com variáveis quantitativas foi utilizado o teste U de Mann-Whitney e para as variáveis qualitativas foi aplicado o teste X2. A significância foi fixada em p ≤ 0,05. Resultados Constatou-se que a idade gestacional tem correlação com o ducto venoso, translucência nucal, fração livre da subunidade β da gonadotrofina coriônica humana, proteína plasmática A associada à gravidez e fator de crescimento placentário; há também correlação entre a história de abortos e o osso nasal. Além disso, correlacionamos o índice de massa corporal com translucência nucal, fração livre da subunidade β da gonadotrofina coriônica humana e proteína plasmática A associada à gravidez. A idade materna foi relacionada com fração livre da subunidade β da gonadotrofina coriônica humana e proteína plasmática A associada à gravidez. Conclusão Nosso estudo demonstra pela primeira vez o comportamento dos marcadores bioquímicos e ultrassonográficos de triagem de cromossomas durante o primeiro trimestre em fetos euploides na Colômbia. Nossa informação é consistente com a referência de valores internacionais. Além disso, mostram-se as relações das diferentes variáveis com as características maternas para determinar as variáveis capazes de ajudar no desenvolvimento de um processo de rastreamento durante o primeiro trimestre com alta taxa de detecção.

Genetic determinants and stroke in children with sickle cell disease.

OBJECTIVE: To verify genetic determinants associated with stroke in children with sickle cell disease (SCD). METHODS: Prospective cohort with 110 children submitted to neonatal screening by the Neonatal Screening Program, between 1998 and 2007, with SCD diagnosis, followed at a regional reference public service for hemoglobinopathies. The analyzed variables were type of hemoglobinopathy, gender, coexistence with alpha thalassemia (α-thal), haplotypes of the beta globin chain cluster, and stroke. The final analysis was conducted with 66 children with sickle cell anemia (SCA), using the chi-squared test in the program SPSS® version 14.0. RESULTS: Among children with SCD, 60% had SCA. The prevalence of coexistence with α-thal was 30.3% and the Bantu haplotype (CAR) was identified in 89.2%. The incidence of stroke was significantly higher in those with SCA (27.3% vs. 2.3%; p=0.001) and males (24.1% vs. 9.6%; p=0.044). The presence of α-thal (p=0.196), the CAR haplotype (p=0.543), and socioeconomic factors were not statistically significant in association with the occurrence of stroke. CONCLUSION: There is a high incidence of stroke in male children and in children with SCA. Coexistence with α-thal and haplotypes of the beta globin chain cluster did not show any significant association with stroke. The heterogeneity between previously evaluated populations, the non-reproducibility between studies, and the need to identify factors associated with stroke in patients with SCA indicate the necessity of conducting further research to demonstrate the relevance of genetic factors in stroke related to SCD.

Genomics and animal production / Genómica y producción animal

Abstract Developing countries have the challenge of achieving food security in a world context that is affected by climate change and global population growth. Molecular Genetics and genomics are proposed as technologies that will help to achieve sustainable food security. Technologies that have been developed in the last decade such as the development of genetic markers, genetic maps, genomic selection, next-generation sequencing, and DNA editing systems are discussed. Examples of some discoveries and achievements are provided.

Resumen Los países en vías de desarrollo tienen el reto de alcanzar seguridad alimentaria en un contexto mundial afectado por el cambio climático y crecimiento poblacional global. La genética molecular y la genómica son propuestas como tecnologías que ayudarán a alzanzar una seguridad alimentaria sostenible. Tecnologías que han sido desarrolladas en la última década como el desarrollo de marcadores moleculares, mapeo genético, selección genómica, secuenciamiento de próxima generación y sistemas de edición de ADN son discutidos. Se proveen ejemplos de algunos descubrimientos y logros.

Implicaciones éticas de la identificación del potencial atlético infantil mediante pruebas genéticas / Ethical implications of the identification of children´s athletic potential through genetic testing

Introducción: La irrupción de la investigación genética en la esfera del deporte ha permitido la localización en el genoma de un considerable número de genes implicados en el rendimiento deportivo y, con ello, el desarrollo de tecnologías genéticas orientadas a la identificación del potencial atlético en niños, cuya aplicación, dada su relativa juventud, debe ser sometida al escrutinio de la comunidad científica desde el prisma de la ética. Objetivo: Evaluar, desde una perspectiva ética, el uso de tecnologías genéticas en la identificación del potencial atlético en niños. Material y métodos: Para la elaboración de la presente revisión, además de la consulta de publicaciones no seriadas, se efectuó una pesquisa en la base de datos Scopus. Resultados: En la actualidad se conocen más de 200 marcadores genéticos relacionados con la predisposición para la aptitud física y al menos 120 vinculados directamente con el rendimiento atlético de élite, información que ha sido utilizada por numerosas compañías para desarrollar los llamados Tests Directos al Consumidor, que pretenden identificar el potencial atlético en niños a partir de su genotipo, sin necesidad de consultar a un especialista. Conclusiones: El uso de tecnologías genéticas en la determinación del potencial atlético en niños no solo viola el espíritu del deporte, sino que también tiene el potencial de causar efectos nocivos en el individuo a nivel psicológico y social; razones por las que es éticamente inadmisible su uso en futuros atletas(AU)

Introduction: The emergence of genetic research in the field of sports has allowed the location of the genome of a considerable number of genes involved in sports performance and thus, the development of genetic technologies aimed at the identification of the athletic potential in children whose application, given its relative youth, should be subject to the review of the scientific community through the prism of ethics. Objective: To evaluate, from an ethical perspective, the use of genetic technologies in the identification of the athletic potential in children. Materials and methods: A search in Scopus database and the consultation of non-serial publications were carried out for the development of this review. Results: Currently, there are more than 200 genetic markers related to the predisposition for physical fitness and, at least, 120 of them are directly linked to elite athletic performance. This information has been used by many companies to develop the so-called Direct-to-Consumer Tests, which aim to identify the athletic potential in children from their genotype, without any need to consult a specialist. Conclusions: The use of genetic technologies in the determination of athletic potential in children not only violates the spirit of sport, but also has the potential to cause harmful effects on the individual at psychological and social levels, reasons why their use is ethically inadmissible in future athletes(AU)

¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal? / Is it clinically worthwhile to evaluate the state of the KRAS, NRAS, BRAF, PTEN, and HER2 genes in patients with colorectal cancer?

En la última década han surgido los tratamientos guiados por el perfil molecular del tumor, con beneficio clínico para los pacientes con cáncer colorrectal avanzado o metastásico. Esta estratificación molecular permite agrupar o individualizar a los pacientes para un óptimo tratamiento de su enfermedad. Basada en información relevante y actualizada, se presenta una revisión de genes y biomoléculas de las vías de señalización intracelular del receptor del factor de crecimiento epidérmico, involucradas en la carcinogénesis del cáncer colorrectal. Además, se pretende identificar evidencia que soporte el beneficio de utilizar biomarcadores en pacientes con cáncer colorrectal, como factores pronósticos o predictivos para tratamientos biológicos. Se concluye que existe evidencia científica y, además, aceptación por parte de asociaciones internacionales de oncología clínica, para utilizar la evaluación del estado de los genes KRAS y BRAF en la práctica clínica, por su valor predictivo en el tratamiento del cáncer colorrectal avanzado; mientras que, para los genes NRAS, PIK3CA, PETEN y HER2, la aceptación por consenso de expertos de Europa y Estados Unidos aún no es unánime, para recomendar la evaluación rutinaria de estos biomarcadores predictivos en el cáncer colorrectal avanzado

Therapies guided by the molecular profile of the tumor have emerged in the last decade, with clinical benefit for patients with advanced or metastatic colorectal cancer. This molecular stratification allows patients to be grouped or individualized for optimal treatment of their disease. Based on relevant and up-to-date information, a mini-review of genes and biomolecules of epidermal growth factor receptor intracellular signaling pathways involved in the carcinogenesis of colorectal cancer is presented. In addition, we intend to identify evidence supporting the benefit of using biomarkers in clinical scenarios of colorectal cancer as prognostic or predictive factors for biological therapies. It is concluded that there is scientific evidence and also acceptance by international associations of clinical oncology to use the evaluation of the state of the KRAS and BRAF genes in clinical scenarios because of its predictive value in the treatment of advanced colorectal cancer, while for the NRAS, PIK3CA, PETEN and HER2 genes the consensus of experts from Europe and the United States of America to recommend the routine evaluation of these predictive biomarkers in advanced colorectal cancer has not yet been unanimous

Genetic determinants and stroke in children with sickle cell disease / Determinantes genéticos e Acidente Vascular Encefálico em crianças com doença falciforme

Abstract Objective: To verify genetic determinants associated with stroke in children with sickle cell disease (SCD). Methods: Prospective cohort with 110 children submitted to neonatal screening by the Neonatal Screening Program, between 1998 and 2007, with SCD diagnosis, followed at a regional reference public service for hemoglobinopathies. The analyzed variables were type of hemoglobinopathy, gender, coexistence with alpha thalassemia (α-thal), haplotypes of the beta globin chain cluster, and stroke. The final analysis was conducted with 66 children with sickle cell anemia (SCA), using the chi-squared test in the program SPSS® version 14.0. Results: Among children with SCD, 60% had SCA. The prevalence of coexistence with α-thal was 30.3% and the Bantu haplotype (CAR) was identified in 89.2%. The incidence of stroke was significantly higher in those with SCA (27.3% vs. 2.3%; p = 0.001) and males (24.1% vs. 9.6%; p = 0.044). The presence of α-thal (p = 0.196), the CAR haplotype (p = 0.543), and socioeconomic factors were not statistically significant in association with the occurrence of stroke. Conclusion: There is a high incidence of stroke in male children and in children with SCA. Coexistence with α-thal and haplotypes of the beta globin chain cluster did not show any significant association with stroke. The heterogeneity between previously evaluated populations, the non-reproducibility between studies, and the need to identify factors associated with stroke in patients with SCA indicate the necessity of conducting further research to demonstrate the relevance of genetic factors in stroke related to SCD.

Resumo Objetivo: Verificar fatores genéticos associados ao acidente vascular encefálico (AVE) em crianças com doença falciforme (DF). Métodos: Coorte prospectiva de 110 crianças submetidas à triagem neonatal pelo Programa de Triagem Neonatal, entre 1998-2007, com o diagnóstico de DF, atendidas em serviço público regional de referência em hemoglobinopatias. As variáveis analisadas foram: tipo de hemoglobinopatia, sexo, coexistência da alfa-Talassemia (α-Tal), haplótipos do cluster da cadeia beta globina e AVE. A análise estatística final foi feita com 66 crianças com anemia falciforme, por meio do teste do qui-quadrado no programa SPSS® 14.0. Resultados: Entre as crianças com DF, 60% eram portadoras de anemia falciforme. A prevalência da coexistência com a α-Tal foi de 30,3% e o haplótipo Bantu (CAR) foi identificado em 89,2%. A incidência de AVE foi significativamente maior nas crianças com AF (27,3% versus 2,3%; p = 0,001) e no sexo masculino (24,1% versus 9,6%; p = 0,044. A presença da α-Tal (p = 0,196), do haplótipo CAR (p = 0,543) e de fatores socioeconômicos não foi significantemente associada à ocorrência de AVE. Conclusão: O AVE apresenta alta incidência em crianças com AF e em crianças do sexo masculino. Coexistência de α-Tal ou de haplótipos do cluster da betaglobina não apresentaram associação significante com AVE. A heterogeneticidade entre as populações previamente avaliadas e a não reprodutibilidade entre estudos indicam a necessidade de novas pesquisas para verificar o papel desses fatores genéticos no AVE em crianças com DF.

Protein molecular modeling of genetic markers for thyroid cancer / Modelagem molecular proteica dos marcadores genéticos do câncer de tireoide

ABSTRACT Introduction: The advances in thyroid molecular biology studies provide not only insight into thyroid diseases but accurate diagnosis of thyroid cancer. Objective: Design a tutorial on protein molecular modeling of genetic markers for thyroid cancer. Methods: The proteins were selected using the Protein Data Bank sequence and the basic local alignment search tool (BLAST) algorithm. The obtained sequences were aligned with the Clustal W multiple alignment algorithms. For the molecular modeling, three-dimensional structures were generated from this set of constraints with the SWISS-MODEL, which is a fully automated protein structure homology-modeling server, accessible via the ExPASy web server. Results: We demonstrated protein analysis, projection of the molecular structure and protein homology of the following molecular markers of thyroid cancer: receptor tyrosine kinase (RET) proto-oncogene; neurotrophic tyrosine kinase receptor 1 (NTRK1) proto-oncogene; phosphatase and tensin homolog (PTEN); tumor protein p53 (TP53) gene; phosphoinositide 3-kinase/threonine protein kinase (PI3K/AKT); catenin beta 1 (CTNNB1); paired box 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARG); rat sarcoma viral oncogene (RAS); B-raf proto-oncogene, serine/threonine kinase (BRAF); and thyroid-stimulating hormone receptor (TSHR). Conclusion: This study shows the importance of understanding the molecular structure of the markers for thyroid cancer through bioinformatics, and consequently, the development of more effective new molecules as alternative tools for thyroid cancer treatment.

RESUMO Introdução: Os avanços nos estudos de biologia molecular da tireoide não fornecem apenas uma visão sobre as doenças tireoidianas, mas um diagnóstico preciso do câncer de tireoide. Objetivo: Realizar um tutorial sobre modelagem molecular proteica dos marcadores genéticos do câncer de tireoide. Métodos: As proteínas foram selecionadas utilizando sequência do Banco de Dados de Proteínas e algoritmo basic local alignment search tool (BLAST). As sequências obtidas foram alinhadas com os algoritmos de alinhamento múltiplo Clustal W. Para a modelagem molecular, as estruturas tridimensionais foram geradas a partir deste conjunto com o SWISS-MODEL, um servidor de homologia de modelagem de estrutura proteica totalmente automatizado, acessível por meio do servidor web ExPASy. Resultados: Demonstramos a análise das proteínas, a projeção da estrutura molecular e a homologia proteica dos seguintes marcadores moleculares de câncer de tireoide: proto-oncogene receptor tyrosine kinase (RET); proto-oncogene neurotrophic tyrosine kinase receptor 1 (NTRK1); phosphatase and tensin homolog (PTEN); gene tumor protein p53 (TP53); phosphoinositide 3-kinase/threonine protein kinase (PI3K/AKT); catenina beta 1 (CTNNB1); paired box 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARG); rat sarcoma viral oncogene (RAS); B-raf proto-oncogene, serine/threonine kinase (BRAF) e thyroid-stimulating hormone receptor (TSHR). Conclusão: Este estudo mostra a importância do conhecimento da estrutura molecular dos marcadores de câncer da tireoide por meio da bioinformática e, consequentemente, o desenvolvimento de novas moléculas mais eficazes como ferramentas alternativas para o seu tratamento.

Prevalence of genetic susceptibility for celiac disease in blood donors in são paulo, brazil / Prevalência da predisposição genética para doença celíaca nos doadores de sangue em São Paulo, Brasil

ABSTRACT Background Celiac disease is a permanent intolerance induced by gluten, which is expressed by T-cell mediated enteropathy, and has a high prevalence in the general population. There is evidence of a strong genetic predisposition to celiac disease. Objective To determine the prevalence of genetic markers HLA-DQ2 and HLA-DQ8 in blood donors from São Paulo and measure human recombinant tissue transglutaminase antibody IgA class in HLA-DQ2 and HLA-DQ8 positive donors. Methods A total of 404 blood donors from São Paulo city and Jundiaí were included in the study and signed the informed consent form. Information regarding diarrhea, constipation and abdominal pain in the last 3 months was collected. Determination of HLADQ2 and HLADQ8 alleles was performed in all participants and human recombinant tissue transglutaminase antibody class IgA was measured only in blood donors who presentedDQ2 and/or DQ8. Results HLADQ2 and/or HLADQ8 were positive in 49% (198/404) of subjects. Positive samples were associated with alleles DR3, DR4, DR7, DR11 and DR12. The most frequent genotype was DR4-DQ8, which was present in 13.6% of samples, followed by genotypes DR3-DQ2 and DR7-DQ2 with DQB1*02 in heterozygous, which were present in 10.4% and 8.7%, respectively. Eleven out of 198 positive donors (5%) were positive to human tissue transglutaminase test. Conclusion We observed a high prevalence of genetic markers for celiac disease, HLA-DQ2 and HLA-DQ8, in blood donors from São Paulo, similar to prevalence described in Europe. These findings show that the prevalence of celiac disease should not be rare in our country, but underdiagnosed.

RESUMO Contexto A doença celíaca é uma enteropatia imuno mediada causada pela intolerância permanente induzida pelo glúten, que se expressa por enteropatia mediada por linfócitos T, e possui uma alta prevalência na população geral. Há evidências de forte predisposição genética para doença celíaca. Objetivo Determinar a prevalência dos marcadores genéticos HLA-DQ2 e HLA-DQ8 em doadores de sangue da cidade de São Paulo e realizar rastreamento sorológico para doença celíaca com anticorpo antitransglutaminase tissular recombinante humana de classe IgA naqueles doadores de sangue com genotipagem HLA-DQ2 e HLA-DQ8 positivos. Métodos Estudo transversal prospectivo em que participaram 404 doadores de sangue, residentes na cidade de São Paulo e Jundiaí. A determinação dos alelos HLADQ2 e HLADQ8 foi realizada por PCR multiplex e alelo específico em todos os participantes do estudo e o anticorpo antitransglutaminase tissular recombinante humana de classe IgA e dosagem sérica de IgA foi realizada apenas nos doadores de sangue que possuíam DQ2 e/ou DQ8 positivo. Resultados O HLADQ2 e/ou DQ8 foi positivo em 49% (198/404) dos indivíduos, destes, 11 (5%) apresentaram anticorpo antitransglutaminase tissular humana positivo. Conclusão Podemos concluir que a prevalência dos marcadores genéticos para doença celíaca, HLA-DQ2 e DQ8 em São Paulo, mostrou-se elevada e similar à encontrada na Europa, assim como foi elevada a soroprevalênca para doença celíaca nos doadores de sangue com presença HLA-DQ2 e DQ8. Estes achados permitem afirmar que a prevalência da doença celíaca não deve ser rara em São Paulo, mas sim subdiagnosticada.

Marcadores moleculares como herramientas en la identificación y análisis genético de especies vectores de interés en salud pública, género Lutzomyia (Grupo Verrucarum Theodor, 1965) / Molecular markers as tools in the identification and genetic analysis of vector species of interest in public health, type Lutzomyia (Verrucarum Theodor group, 1965)

Introducción: Los insectos flebotomíneos del grupo Verrucarum, son vectores de interés en salud pública dada su participación en la transmisión de las enfermedades tropicales: leishmaniasis y bartonelosis. El empleo de marcadores moleculares como herramienta de identificación y análisis genético de especies que se comportan como vectores potenciales y confirmados, muestran un uso ampliamente difundido, que genera un conjunto de información que se actualiza constantemente, más aun cuando la identificación de estas especies, es prioritaria en los países donde estas enfermedades ocurren de forma recurrente. Objetivo: Se presenta una revisión sistemática con el objetivo de recopilar y presentar una actualización sobre el uso de marcadores moleculares empleados en especies del grupo Verrucarum. Materiales y métodos: Esta búsqueda se efectuó en un rango de literatura relevante publicada en un periodo de 24 años que incluyó 23 artículos en la temática de genética y biología molecular de flebótomos y 39 artículos de otras áreas como sistemática, ecología de flebótomos y microbiología de agentes patógenos asociados. Resultados: Los resultados muestran el empleo de los genes que codifica para el ARN ribosomal 18S y para el citocromo oxidasa subunidad I como los más efectivos para observar las relaciones filogenéticas entre especies del grupo Verrucarum; el uso del gen citocromo b como carácter taxonómico alternativo para identificar correctamente los flebótomos y, el uso de secuencias espaciadoras de la transcripción interna del ARN ribosomal y el gen citocromo b para determinar la variación genética intra e interespecífica de las poblaciones. Conclusión: Esta revisión contribuirá a estudios filogenéticos de vectores de importancia en salud pública.

Introduction: The phlebotomine flies of the Verrucarum group are vectors of interest in public health because of their participation in the transmission of the tropical diseases: leishmaniasis and bartonellosis. The use of molecular markers, as a tool for the identification and genetic analysis of species that behave as potential and confirmed vectors, show a widely disseminated use that generates a set of information that is constantly updated, even more when the identification of these species is a priority in the countries where these diseases occur on a recurring basis. Objective: The paper presents a systematic review that aims at compiling and presenting an update on the use of molecular markers employed in species of the Verrucarum group. Materials and methods: This search was conducted in a range of relevant literature published in a period of 24 years which included 23 articles on the subject of genetics and molecular biology of sand flies, and 39 articles from other areas such as systematic, ecology of sand flies and microbiology of related pathogenic agents. Results: The results show the use of genes coding for ribosomal 18S RNA and cytochrome oxidase subunit I as the most effective to observe the phylogenetic relationships among species of the Verrucarum group; the use of the cytochrome b gene as alternative taxonomic character to correctly identify the sand flies, and the use of spacer sequences of the internal transcript of the ribosomal RNA and the Cytochrome b gene to determine the genetic variation of intra- and inter-specific populations. Conclusions: This review will contribute to phylogenetic studies of vectors of public health importance.

Análisis de la interacción entre el polimorfismo Rs671 del gen ALDH2 y consumo de alcohol en individuos chilenos / Interaction between Rs671 polymorphism of the ALDH2 gene and alcohol consumption in Chilean individuals

El alcoholismo es un importante problema de salud pública. En los últimos años ha causado interés el metabolismo del alcohol, puesto que ha sido considerado un posible determinante biológico en la conducta de consumo. Variados estudios se han orientado a la búsqueda y comprensión de la influencia de polimorfismos, en genes que codifican para los principales sistemas enzimáticos que intervienen en el metabolismo hepático. El polimorfismo rs671 del gen que codifica la enzima ALDH2 ha sido asociado a un menor consumo de alcohol debido a la acumulación de acetaldehído en sangre. Diversos estudios indican que este polimorfismo es frecuente en países asiáticos y se considera un factor protector en los individuos que lo portan. Se incluyeron 207 individuos adultos no relacionados, a los cuales se les aplicó un cuestionario sobre consumo de alcohol. El polimorfismo rs671 fue analizado por la reacción de la polimerasa en cadena (PCR) seguida de restricción enzimática. Además, se determinaron los biomarcadores clásicos indirectos de consumo de alcohol, mediante técnicas enzimáticas y hematológicas. La frecuencia del genotipo homocigoto mutado AA para el polimorfismo rs671 fue 3,0% en sujetos consumidores de alcohol y 2,8% en el grupo no consumidor. La distribución de genotipos y las frecuencias alélicas para esta variante fueron semejantes entre los sujetos estudiados (p>0,05). Estos hallazgos sugieren que la variante rs671 del gen ALDH2 no está asociada al oconsumo de alcohol en los individuos estudiados.

Alcoholism is an important public health problem. In recent years, alcohol metabolism caused interest, since it has been considered a possible biological determinant of alcohol consumption behavior. Several studies have focused on finding and understanding the influence of polymorphisms affecting genes that encode for enzymatic systems involved in the hepatic metabolism. The rs671 polymorphism of the gene encoding ALDH2 has been associated with lower alcohol consumption by leading to acetaldehyde accumulation in blood. This genetic variant is frequently found in Asian population and has been considered as protector factor of alcoholism in these individuals. In the present study, 207 unrelated-adult individuals were included. Alcohol consumption was recorded using a structured questionnaire. The rs671 polymorphism was analyzed using polymerase chain reaction followed by enzymatic digestion. Furthermore, classical biomarkers for alcohol consumption were assessed using enzymatic and hematological techniques. The frequency of homozygote genotype for the A allele (AA) was 3 and 2.8% in those subjects defined as alcohol drinkers and non-alcohol drinkers respectively. The genotypes distribution and allelic frequencies were similar among the studied subject (p>0.05). These data suggest that rs671 ALDH2 gene polymorphism is not associated to alcohol consumption in the studied population.