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Ethics. Human subjects: All cohort participants gave written informed consent and consent to publish. Ethical approvals were provided for the Rotterdam Study according to the Population Study Act Rotterdam Study (Wet Bevolkingsonderzoek ERGO) executed by the Ministry of Health, Welfare and Sports of the Netherlands, for the TwinsUK study by the St. Thomas’ Hospital Local Research Ethics Committee, for the QIMR study by the Queensland Institute of Medical Research Human Research Ethics Committee, and...

Human subjects: All cohort participants gave written informed consent and consent to publish. Ethical approvals were provided for the RS according to the Population Study Act Rotterdam Study (Wet Bevolkingsonderzoek ERGO) executed by the Ministry of Health, Welfare and Sports of The Netherlands, for the TwinsUK study by the St. Thomas’ Hospital Local Research Ethics Committee, for the QIMR study by the QIMR Human Research Ethics Committee, and for the US study by the Indiana University Internal...

[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n= 59,771) and generalized our findings in 9 additional studies (stage 2, n= 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Trabajo de Síntesis Aplicada En el terminal de carga aéreo de Bogotá se ha identificado la necesidad de suplir a través de un punto comercial el servicio de impresiones, fotocopias, venta de productos no perecederos y herramientas de ferretería, por lo que este trabajo muestra qué tan viable es la puesta en marcha de un proyecto de inversión bajo modelo Joint Venture brindando información financiera mediante la proyección de estados financieros, y algunos resultados importantes como margen operacional, punto de equilibrio, margen de contribución por unidad y tasa interna de retorno. Especialización Especialista en Análisis y Administración Financiera RESUMEN 1. Introducción 2. Planteamiento del problema 3. Pregunta de investigación 4. Justificación 5. Objetivo general 6. Objetivos específicos 7. Marco conceptual / variables técnicas 8. Estructura estratégica 9. Marco legal 10. Marco metodológico y presentación de resultados 11. Estudio financiero Recomendaciones Conclusiones

International audience; We developed a new mutationally well-balanced 32 Y-STR multiplex ( CombYplex) together with a machine learning (ML) program PredYMa Le to assess the impact of STR mutability on haplogourp prediction, while respecting forensic community criteria (high DC/HD). We designed CombYplex around two sub-panels M1 and M2 characterized by average and high-mutation STR panels. Using these two sub-panels, we tested how our program PredYmale reacts to mutability when considering basal branches and, moving down, terminal branches. We tested first the discrimination capacity of CombYplex on 996 human samples using various forensic and statistical parameters and showed that its resolution is sufficient to separate haplogroup classes. In parallel, Pred YMa Le was designed and used to test whether a ML approach can predict haplogroup classes from Y-STR profiles. Applied to our kit, SVM and Random Forest classifiers perform very well (average 97 %), better than Neural Network (average 91 %) and Bayesian methods (< 90 %). We observe heterogeneity in haplogroup assignation accuracy among classes, with most haplogroups having high prediction scores (99–100 %) and two (E1b1b and G) having lower scores (67 %). The small sample sizes of these classes explain the high tendency to misclassify the Y-profiles of these haplogroups; results were measurably improved as soon as more training data were added. We provide evidence that our ML approach is a robust method to accurately predict haplogroups when it is combined with a sufficient number of markers, well-balanced mutation rate Y-STR panels, and large ML training sets. Further research on confounding factors (such as CNV-STR or gene conversion) and ideal STR panels in regard to the branches analysed can be developed to help classifiers further optimize prediction scores.

IntroductionPain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association studies (GWAS) is still in its infancy. This protocol describes a proposed GWAS on genetic contributions to baseline pain sensitivity and nociceptive sensitisation in a sample of unrelated healthy individuals of mixed Latin American ancestry.Methods and analysisA GWAS on genetic contributions to pain sensitivity in the naïve state and following nociceptive sensitisation will be conducted in unrelated healthy individuals of mixed ancestry. Mechanical and thermal pain sensitivity will be evaluated with a battery of quantitative sensory tests evaluating pain thresholds. In addition, variation in mechanical and thermal sensitisation following topical application of mustard oil to the skin will be evaluated.Ethics and disseminationThis study received ethical approval from the University College London research ethics committee (3352/001) and from the bioethics committee of the Odontology Faculty at the University of Antioquia (CONCEPTO 01–2013). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations at international conferences.

Introduction: Host genetics is recognized as an influential factor for the development of dengue disease. Objective: This study evaluated the association of dengue with the polymorphisms rs8192284 for gene IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN. Materials and methods: Of the 292 surveyed subjects, 191 were confirmed for dengue fever and the remaining 101 were included as controls. The genotypes were resolved using polymerase chain reaction and restriction fragment length polymorphism (PCR- RFLP). In an attempt to determine the risk (Odds Ratio) of suffering dengue fever, data were analyzed using chi-square for alleles and logistic regression for both genotypes and allelic combinations. Confidence intervals were set to 95% for all tests regardless of the adjustment by either self-identification or ancestry. Results: For Afro-Colombians, the allele rs8192284 C offered protection against dengue [OR=0.425,(0.204-0.887), p=0.020]. The alleles rs7248637 A and rs3775290 A posed, respectively, an increased risk of dengue for Afro-Colombians [OR=2.389, (1.170-4.879), p=0.015] and Mestizos [OR=2.329, (1.283-4.226), p=0.005]. The reproducibility for rs8192284 C/C [OR=2.45, (1.05-5.76), p=0.013] remained after adjustment by Amerindian ancestry [OR=2.52, (1.04-6.09), p=0.013]. The reproducibility for rs3775290 A/A [OR=2.48, (1.09-5.65), p=0.033] remained after adjustment by European [OR=2.34, (1.02-5.35), p=0.048], Amerindian [OR=2.49, (1.09-5.66), p=0.035], and African ancestry [OR=2.37, (1.04-5.41), p=0.046]. Finally, the association of dengue fever with the allelic combination CAG [OR=2.07, (1.06-4.05), p=0.033] remained after adjustment by Amerindian ancestry [OR=2.16, (1.09-4.28), p=0.028]. Conclusions: Polymorphisms rs8192284 for IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN were associated with the susceptibility to suffer dengue fever in the sampled Colombian population. Resumen Introducción. La genética del huésped se reconoce como un factor que influye en el desarrollo del dengue. Objetivo. Este estudio evaluó la asociación del dengue con los polimorfismos rs8192284 del gen IL6R, rs3775290 del TLR3 y rs7248637 del DC-SIGN. Materiales y métodos. De los 292 sujetos encuestados, en 191 se confirmó la presencia de fiebre por dengue y los restantes 101 se incluyeron como controles. Los genotipos se resolvieron mediante reacción en cadena de la polimerasa y polimorfismos en la longitud de los fragmentos de restricción (PCR-RFLP). En un intento por determinar el riesgo de sufrir dengue, los datos se analizaron mediante la prueba de ji al cuadrado para los alelos y la regresión logística para los genotipos y las combinaciones alélicas. Los intervalos de confianza se calcularon a 95 % para todas las pruebas independientemente ajustadas por autoidentificación o componente genético ancestral. Resultados. En los afrocolombianos, el alelo C rs8192284 ofreció protección contra el dengue (OR=0,425; 0,204-0,887, p=0,020). Los alelos A rs7248637 y Ars3775290 plantearon un mayor riesgo de dengue para los afrocolombianos (OR=2,389; 1,170- 4,879; p=0,015) y los mestizos (OR=2,329; 1,283-4,226: p=0,005), respectivamente. La reproducibilidad para rs8192284 C/C (OR=2,45; 1,05-5,76; p=0,013) permaneció después del ajuste por el componente genético ancestral amerindio (OR=2,52; 1,04- 6,09; p=0,013). La reproducibilidad del rs3775290 A/A (OR=2,48; 1,09-5,65; p=0,033) permaneció después del ajuste por el componente europeo (OR=2,34; 1,02-5,35; p=0,048), el amerindio (OR=2,49; 1,09- 5,66; p=0,035), y el africano (OR=2,37; 1,04- 5,41; p=0,046). Por último, la asociación del dengue con la combinación alélica CAG (OR=2,07; 1,06-4,05; p=0,033) permaneció después del ajuste por el componente genético amerindio (OR=2,16; 1,09-4,28;p=0,028). Conclusión. Los polimorfismos rs8192284 en IL6R, rs3775290 en TLR3 y rs7248637 en DC-SIGN, se asociaron con la propensión a sufrir dengue en una muestra de población colombiana.

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans., Pigmentation variation in humans is influenced by complex genetic architecture in different populations. Here, the authors perform a genome-wide association analysis involving > 6,000 Latin Americans for pigmentation of skin and eyes, and identify known and novel genetic associations.

OBJECTIVES: This article aims to assess the contribution of genomic ancestry and socioeconomic status to obesity in a sample of admixed Latin Americans. METHODS: The study comprised 6776 adult volunteers from Brazil, Chile, Colombia, Mexico, and Peru. Each volunteer completed a questionnaire about socioeconomic variables. Anthropometric variables such as weight, height, waist, and hip circumference were measured to calculate body indices: body mass index, waist-to-hip ratio and waist-to-height ratio (WHtR). Genetic data were extracted from blood samples, and ancestry was estimated using chip genotypes. Multiple linear regression was used to evaluate the relationship between the indices and ancestry, educational level, and economic well-being. The body indices were dichotomized to obesity indices by using appropriate thresholds. Odds ratios were calculated for each obesity index. RESULTS: The sample showed high percentages of obesity by all measurements. However, indices did not overlap consistently when classifying obesity. WHtR resulted in the highest prevalence of obesity. Overall, women with low education level and men with high economic wellness were more likely to be obese. American ancestry was statistically associated with obesity indices, although to a lesser extent than socioeconomic variables. CONCLUSIONS: The proportion of obesity was heavily dependent on the index and the population. Genomic ancestry has a significant influence on the anthropometric measurements, especially on central adiposity. As a whole, we detected a large interpopulation variation that suggests that better approaches to overweight and obesity phenotypes are needed in order to obtain more precise reference values.

Most population isolates examined to date were founded from a single ancestral population. Consequently, there is limited knowledge about the demographic history of admixed population isolates. Here we investigate genomic diversity of recently admixed population isolates from Costa Rica and Colombia and compare their diversity to a benchmark population isolate, the Finnish. These Latin American isolates originated during the 16th century from admixture between a few hundred European males and Amerindian females, with a limited contribution from African founders. We examine whole-genome sequence data from 449 individuals, ascertained as families to build mutigenerational pedigrees, with a mean sequencing depth of coverage of approximately 36×. We find that Latin American isolates have increased genetic diversity relative to the Finnish. However, there is an increase in the amount of identity by descent (IBD) segments in the Latin American isolates relative to the Finnish. The increase in IBD segments is likely a consequence of a very recent and severe population bottleneck during the founding of the admixed population isolates. Furthermore, the proportion of the genome that falls within a long run of homozygosity (ROH) in Costa Rican and Colombian individuals is significantly greater than that in the Finnish, suggesting more recent consanguinity in the Latin American isolates relative to that seen in the Finnish. Lastly, we find that recent consanguinity increased the number of deleterious variants found in the homozygous state, which is relevant if deleterious variants are recessive. Our study suggests that there is no single genetic signature of a population isolate.

Objectives: This article aims to assess the contribution of genomic ancestry and socioeconomic status to obesity in a sample of admixed Latin Americans. Methods: The study comprised 6776 adult volunteers from Brazil, Chile, Colombia, Mexico, and Peru. Each volunteer completed a questionnaire about socioeconomic variables. Anthropometric variables such as weight, height, waist, and hip circumference were measured to calculate body indices: body mass index, waist-to-hip ratio and waist-to-height ratio (WHtR). Genetic data were extracted from blood samples, and ancestry was estimated using chip genotypes. Multiple linear regression was used to evaluate the relationship between the indices and ancestry, educational level, and economic well-being. The body indices were dichotomized to obesity indices by using appropriate thresholds. Odds ratios were calculated for each obesity index. Results: The sample showed high percentages of obesity by all measurements. However, indices did not overlap consistently when classifying obesity. WHtR resulted in the highest prevalence of obesity. Overall, women with low education level and men with high economic wellness were more likely to be obese. American ancestry was statistically associated with obesity indices, although to a lesser extent than socioeconomic variables. Conclusions: The proportion of obesity was heavily dependent on the index and the population. Genomic ancestry has a significant influence on the anthropometric measurements, especially on central adiposity. As a whole, we detected a large interpopulation variation that suggests that better approaches to overweight and obesity phenotypes are needed in order to obtain more precise reference values. Fil: Ruderman, Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Adhikari, Kaustubh. Colegio Universitario de Londres; Reino Unido. Open University; Reino Unido Fil: Navarro, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Ramallo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú Fil: Bedoya Berrío, Gabriel. Universidad de Antioquia; Colombia Fil: Bortolini, María Cátira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Acuña Alonzo, Victor. Instituto Nacional de Antropología E Historia; México Fil: Canizales Quinteros, Samuel. Instituto Nacional de Medicina Genómica; México Fil: Rothhammer, Francisco. Universidad de Chile; Chile Fil: Ruiz-Linares, Andres. Colegio Universitario de Londres; Reino Unido. Fudan University; China Fil: González José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina

International audience

Resumen Introducción. La composición genética del huésped determina, entre otros aspectos, el perfil clínico del dengue, lo cual se debería al efecto de variantes en los genes que codifican citocinas proinflamatorias. Objetivo. Evaluar la asociación entre las variantes de tres polimorfismos en los genes candidatos TNFA, IL6 e IFNG con la gravedad del dengue en una población colombiana. Materiales y métodos. Se evaluaron los polimorfismos rs1800750, rs2069843 y rs2069705 de los genes TNFA, IL6 e IFNG, respectivamente, en 226 pacientes con dengue. Los genotipos se tipificaron usando la reacción en cadena de la polimerasa (PCR) y los polimorfismos de la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Para determinar el riesgo de diferentes fenotipos del dengue, se compararon las frecuencias alélicas con la prueba de ji al cuadrado, y los genotipos y los haplotipos, con regresión logística. Por último, los análisis se ajustaron utilizando datos de autoidentificación o del componente genético ancestral. Resultados. El alelo A del rs2069843, ajustado por autoidentificación, se asoció con casos de dengue hemorrágico en afrocolombianos. En la muestra completa, dicho polimorfismo, ajustado por componente genético ancestral, fue reproducible. Además, hubo asociaciones significativas entre las combinaciones alélicas GGT y GAC de los rs1800750, rs2069843 y rs2069705 en pacientes con dengue hemorrágico, con ajuste por componente genético ancestral y sin él. Además, la combinación alélica AGC produjo 58,03 pg/ml más de interleucina 6 que la GGC, independientemente de los componentes genéticos europeo, amerindio y africano. Conclusión. Las variantes de los polimorfismos GGT y GAC de los rs1800750, rs2069843 y rs2069705 en los genes TNFA, IL6 e IFNG, respectivamente, se correlacionaron con la gravedad del dengue en esta muestra de población colombiana. Abstract Introduction: The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines. Objective: To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population. Materials and methods: We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chisquare and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component. Results: The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components. Conclusions: The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.

En este trabajo se evalúa la relación entre la asimetría fluctuante facial (AFF) y los tratamientos hormonales, cirugías maxilofaciales, ortodoncia, traumatismos y malformaciones. En el marco del proyecto CANDELA, se tomaron cinco fotografías faciales de 3162 voluntarios entre los 18 y 85 años. Por fotogrametría se colocaron 34 landmarks o puntos en 3D y mediante el método Procrustes ANOVA se obtuvieron valores individuales de asimetría fluctuante facial. Se realizó una prueba de ANOVA de una vía y la prueba de Welch y Levene para conocer las diferencias entre media y varianza de los valores de asimetría facial y las variables respuesta. También, se caracterizó la variación morfológica del componente asimétrico de la forma facial mediante técnicas multivariadas sobre los grupos que resultaran diferentes significativamente. Las mujeres que reportaron haber recibido algún tipo de tratamiento hormonal mostraron mayores valores de asimetría fluctuante facial respecto al grupo sin tratamiento. Esta asociación se mantuvo una vez removido el efecto de la heterocigosidad (como indicador de la ancestría) y sin interactuar con el resto de covariables incluidas en el análisis. Los cambios morfológicos asociados a este factor se concentran en el mentón, maxilar labio inferior, región perifrontal, región nasal y orejas. Algunos trabajos anteriores dieron cuenta de la posible relación entre la asimetría facial y los niveles de hormonas, pero no hay estudios que sustenten la relación causal o directa entre la asociación aquí planteada. El presente trabajo es una evidencia más de la asociación entre el consumo de hormonas y modificaciones de caracteres faciales en poblaciones urbanas mestizas latinoamericanas. In this work we test for the putative association between facial fluctuating asymmetry (FFA) and hormone treatments, maxillofacial surgery, orthodontics, injuries, and malformations. A protocol of five photographs and photogrammetric reconstruction was implemented to place thirty-four 3D landmarks in 3162 individuals aged between 18 and 85 years, belonging to the CANDELA initiative. A Procrustes ANOVA test was used to obtain individual facial fluctuating asymmetry scores. One way ANOVA, Welch, and Levene tests were conducted to explore the potential differences between mean and variance of the response variables. Our results indicate that women who received some hormonal treatment showed higher fluctuating facial asymmetry scores in relation to the unaffected group, this being persistent once the effects of heterozygosity (genetic ancestry) and further variables had been statistically controlled. The shape changes corresponding to this association are focused on the chin, jaw, lower lip, prefrontal region, nose, and ears. Previous reports suggested a potential relationship between facial asymmetry and hormone levels, but to the best of our knowledge there are no reports indicating the causation underlying the association detected here. This report is one more evidence of the association between hormone intake and facial asymmetric features in urban admixed Latin American populations. Asociación de Antropología Biológica de la República Argentina

Introduction: Mitochondrial DNA has proven its utility for the study of insect evolution. Genes such as cytochrome b (Cytb) and the transfer gene for serine (SertRNA) can be used to compare closely related organisms. Objective: The phylogenetic utility of Cytb-SertRNA-IG1-ND1 was tested for polymorphisms, and secondary structure modeling in SertRNA was done to detect possible cryptic species in Anopheles neivai. Materials and methods: Specimens from Colombia, Guatemala, and the type locality in Panamá were collected and sequenced for specimen comparison based on DNA polymorphisms, and secondary structure modeling for the SertRNA gene. Results: Thirty-six sequences for A. neivai and A. pholidotus were obtained. Conclusions: Polymorphic variants were detected in A. neivai for Cytb-SertRNA-IG1- ND1. Despite this variation in A. neivai, cryptic species could not be detected. Resumen Introducción. El ADN mitocondrial ha demostrado su utilidad para el estudio de la evolución en los insectos. Existen algunos genes mitocondriales como el citocromo b (Cytb) y el gen de transferencia para el aminoácido serina (SertRNA) que pueden usarse en el diagnóstico de especies estrechamente relacionadas. Objetivo. Explorar la utilidad filogenética de la región Cytb-SertRNA-IG1-ND1 para detectar posibles especies crípticas en Anopheles neivai. Materiales y métodos. Se recolectaron especímenes en Colombia, Guatemala y en la localidad tipo en Panamá, los cuales se secuenciaron y se compararon mediante el polimorfismo de ADN en toda la región y mediante la simulación de estructuras secundarias del gen SertRNA. Resultados. Se obtuvieron las secuencias de especímenes de A. neivai (34) y A. pholidotus (2). Conclusiones. Se detectaron algunos polimorfismos para la regiónCytb-SertRNA-IG1-ND1 en A. neivai, pero no así especies crípticas.

RESUMEN Introduction: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. Objective: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Materials and methods: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p’ value

Sequence of primer used to PCR. Table S2. Ancestral informative Markers (AIMs), allelic frequencies and delta (δ) of frequencies in the three ancestral populations (European, African and Amerindian). Table S3. Characteristics of the study population, stratified according to gender. Table S4. Association with anthropometric measures at 10 selected genetic variants on the subset of the samples with available ancestry information. Table S5. Interaction between SNP and socioeconomic and perinatal factors in determining body mass index. Figure S1. The histogram of body mass index, body fat percentage and waist circumference by gender. (DOCX 123 kb)

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values, Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.

Prevalence of diseases/trait cardio-metabolic, Age standardized estimate by region. Table S2. Ancestral informative Markers (AIMs), allelic frequencies and delta (δ) of frequencies in the three ancestral populations (European, African and Amerindian). Table S3. Sequence of primers and amplification parameters of the ancestry informative markers (AIMs). Table S4. Individual ancestral composition. Figure S1. Individual ancestral composition. (DOCX 155 kb)

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair., By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al. identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.

The negative homozygous condition for the Duffy blood group (Fy-/Fy-) confers natural resistance to Plasmodium vivax infection. Studies carried out in pursuing this direction in Colombia are scarce.To describe the relationship between Duffy genotypes in three ethnic communities of La Italia (Chocó) and malarial infection.This is a descriptive, cross-sectional study in symptomatic and asymptomatic subjects with malaria.Afro-Colombians 73; Amerindian (Emberá) 74, and Mestizo, 171. The presence of Plasmodium infection was assessed by thick smear and the status of the Duffy gene was studied by PCR and RFLP to help identify changes to T-46C and A131G which originate the genotypes T/T, T/C , C/C and G/G, G/A, A/A.Infection by Plasmodium was detected in 17% of cases with 62% due to P. falciparum and 27% due to P. vivax. Duffy genotypes were significantly associated with ethnicity (p= 0.003). Individuals with the C/C, A/A diplotypes were exclusively infected by P. falciparum, whereas the other diplotypes were infected with either of the species. In the Amerindian and Mestizo populations, the frequency of the T-46 allele was 0.90-1.00, among Afro-Colombians this was 0.50, the same as with the C allele and with an absence of heterozygous. At locus 131, the maximum frequency of the G allele was 0.30 in Amerindians and the maximum of the A allele was 0.69 in Afro-Colombians.In the Amerindian and mestizo populations studied, there was a predominance of the allele T-46 (FY+) but this was not observed with the P. vivax infection. P. vivax was ruled out in all FY- individuals.La condición homocigótica negativa del grupo sanguíneo Duffy ((Fy-/Fy-) confiere resistencia natural adescribir la relación entre los genotipos Duffy en tres comunidades étnicas de La Italia (Chocó), y la malaria.estudio descriptivo, transversal con individuos sintomáticos o asintomáticos de malaria. Tamaño muestral por etnia: afrocolombiana 73; amerindia 74, mestiza 171. La infección plasmodial se estudió por gota gruesa y el estado del gen Duffy por PCR y RFLP con el fin de identificar los cambios T-46C y A131G que originan los genotipos T/T, T/C , C/C y G/G, G/A, A/A.se encontró infección plasmodial en 17% con 62% porEn las poblaciones amerindia y mestiza estudiadas predomina el alelo T-46 (FY+), pero no predomina en ellas la infección por

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1., The shape of the pinna varies widely in the general human population but the genetic basis of this variation is unknown. Here Adhikari et al. conduct a genome-wide association study in Latin Americans and discover seven gene regions influencing pinna morphology, including EDAR and TBX15.

Introducción: la extravasación del plasma es la manifestación más severa de la enfermedad producida por los virus del dengue y que con mayor frecuencia conduce al estado de choque. Se caracteriza por derrames serosos a nivel de diversas cavidades y aumento del hematocrito. Se realizó el presente estudio con el objetivo de determinar los factores sociodemográficos, clínicos y de laboratorio que más se asocian a la presencia de extravasación plasmática en los pacientes con dengue. Materiales y métodos: estudio observacional analítico transversal, analizado bajo la metodología de casos y controles, a partir de registros clínicos de pacientes con dengue. Se utilizaron prueba Chi cuadrado de Pearson, prueba exacta de Fisher, prueba no paramétrica U de Mann-Whitney y un modelo de regresión logística multivariado de factores asociados. Fueron calculados los Odds Ratio con su intervalo de confianza al 95 %. Se consideró un nivel de significancia de 5 %. Resultados: fueron analizados un total de 350 registros, de los cuales 128 presentaron signos de extravasación plasmática (36,6 %). Después de ajustar por factores de confusión se observó que las variables que más se asocian a presencia de extravasación plasmática en los pacientes con dengue fueron el dolor abdominal, la leucopenia y las melenas. Conclusión: estos hallazgos clínicos y de laboratorio deben ser priorizados en su vigilancia en la atención al paciente con dengue, para identificar los casos con mayor probabilidad de extravasación plasmática para su manejo oportuno y adecuado. Introduction: Plasma leakage is the most severe complication caused by dengue virus infection and is also the mechanism that frequently leads to dengue shock syndrome. Plasma leakage is characterized by ascites, pleural and pericardial effusion and increased hematocrit level. The present study was conducted to identify socio-demographic, clinical and laboratory factors that more are associated to the presence of plasma leakage in dengue infected patients. Materials and methods: A cross sectional analytic study was performed on clinical records from dengue infected patients using the casecontrol methodology. Pearson's chi-square test or Fisher's exact test, Mann-Whitney's non-parametric U test and a multivariate logistic regression model of associated factors were used to evaluate the data. Odd Ratios with 95 % confidence intervals were calculated and significance level of 5 % was considered. Results: A total of 350 clinical records were analyzed, 128 cases (36.6 %) presented signs of plasma leakage. After adjustments by confounding factors, we observed that abdominal pain, leukopenia and melena were the variables that explain the presence of plasma leakage in dengue infected patients. Conclusion: During the follow-up of dengue infected patients priority should be given to the survey of these clinical and laboratory findings in order to identify the cases with higher probabilities of developing plasma leakage, allowing achieving more timely and appropriate management.

Introducción. Las poblaciones de Aedes aegypti pueden experimentar cambios en cuanto a su abundancia y diversidad genética y, con ello, su potencial evolutivo para responder al control vectorial. El conocimiento de los cambios en la variación genética a escala espacio-temporal, permite entender mejor la epidemiología del dengue y contribuye al diseño adecuado y oportuno de estrategias antivectoriales. Objetivo. Evaluar los cambios genéticos, la diversidad y el flujo génico en seis poblaciones microgeográficas de Ae. aegypti en Medellín en diferentes períodos epidemiológicos del dengue. Materiales y métodos. En 255 especímenes provenientes de seis barrios de Medellín, se evaluó la variación en la composición de los haplotipos mtDNA CO1 , así como la diversidad y la diferenciación genética en un período epidémico (2010) y en otro endémico (2012). Resultados. Se detectaron dos grupos de haplotipos muy diferenciados entre sí en ambos períodos, al igual que un haplotipo de alta frecuencia presente en todos los barrios. La mayor diversidad de haplotipos se registró en el 2012, pero la mayor diversidad de nucleótidos se presentó en el 2010. No se observó correlación significativa entre las distancias genéticas y geográficas. Conclusión. La composición genética de Ae. aegypti varía temporalmente sin un patrón predecible. La presencia de un haplotipo de gran frecuencia en ambos períodos podría ser indicio de una variación persistente adaptada al control vectorial. Sin embargo, la circulación simultánea de haplotipos CO1 muy diferenciados y compatibles con múltiples introducciones, sugiere que diversos acervos genéticos serían aptos para la transmisión. Estos resultados son compatibles con la dispersión del mosquito por efecto de actividades antrópicas, lo cual posibilitaría la diseminación rápida del virus durante epidemias en Medellín. Introduction: Aedes aegypti populations may experience changes in abundance and genetic diversity in addition to changes in their evolutionary capability to respond to vector control. The knowledge on the changes in genetic variation on a spatio-temporal scale improves the epidemiological understanding of dengue and supports the appropriate and timely design of vector control strategies. Objective: To assess the genetic changes, diversity and gene flow in six microgeographical populations of Ae. aegypti in Medellín for different epidemiological periods of dengue. Materials and methods: A total of 255 specimens from six different neighborhoods in Medellín were used to assess variations in the CO1 mtDNA haplotype composition, diversity and genetic differentiation for an epidemic period (2010) and an endemic period (2012). Results: Two groups of highly differentiated haplotypes were present in both periods, and a high-frequency haplotype was assessed for all neighborhoods. The highest haplotype diversity was recorded in 2012, but the maximum nucleotide diversity was recorded in 2010. No significant correlation between genetic and geographic distances was observed. Conclusions: The genetic composition of Ae. aegypti varies over time without a predictable pattern. In addition, the presence of a high-frequency haplotype in both periods could indicate a persistent variation adapted to vector control. However, the simultaneous movement of highly differentiated CO1 haplotypes compatible with multiple introductions suggests that different gene pools would be suitable for transmission. These results are consistent with mosquito dispersion due to human activities, which would enable the rapid spread of the virus during epidemics in Medellin.

Introducción: El exceso de peso en niños y adolescentes es una pandemia que aumenta el riesgo de mortalidad por enfermedades crónicas no transmisibles. Se ha estimado que aun en etapas tempranas de la vida, el exceso de peso se asocia con alteraciones metabólicas; sin embargo, es necesario establecer si en nuestro medio estas alteraciones se evidencian en población menor de 19 años. Objetivo: Comparar el perfil lipídico y la ingesta de frutas y verduras, según el índice de masa corporal, en un grupo de jóvenes de 10 a 19 años, de la empresa promotora de salud SURA, sede de Medellín. Métodos: Estudio de corte transversal, en el que participaron 103 jóvenes obesos, 120 con sobrepeso y 214 con un índice de masa corporal normal. En condiciones basales y ayuno de 10 horas, se evaluó colesterol total, c-LDL, c-HDL y triglicéridos. La ingesta de verduras y frutas se determinó mediante recordatorio de 24 horas. Resultados: Los datos de c-LDL en el grupo de obesos, sobrepeso y control fueron, respectivamente: 95 ± 32, 96 ± 53 y 80 ± 24 mg/dL (p = 0,000); para los mismos grupos, los datos de triglicéridos fueron: 116 ± 65, 112 ± 69 y 88 ± 52 mg/dL (p = 0,000). El c-HDL en los 3 grupos fue: 52 ± 14, 53 ± 12 y 56±14 mg/dL (p = 0,013), respectivamente. Se evidenció una asociación significativa entre el mayor consumo de frutas y la menor concentración de triglicéridos entre los participantes con sobrepeso (p = 0,035). No fue habitual la ingesta de frutas y verduras. Conclusiones: El alto índice de masa corporal promueve un perfil lipídico aterogénico. Son necesarias acciones para promover hábitos alimentarios saludables. Introduction: Childhood overweight is a pandemic that increases the risk of chronic non-communicable diseases. It has been estimated that being overweight is associated with metabolic disorders; even in early stages of life. However, it is necessary to establish whether this association is observed in Colombian population between 10-19 years old. Objective: To compare lipid profile and fruit and vegetable intakes, according to body mass index, in subjects aged 10-19 in a health insurance company (SURA) from Medellin. Methods: One hundred an three obese, 120 overweight, and 214 children with normal body mass index participated in a cross-sectional study. We compared total cholesterol, LDL-C, HDL-C and triglycerides between groups; at baseline and after 10-hour fasting period. Fruit and vegetable intakes were determined by 24-hour dietary record. Results: LDL-C levels in obese, overweight and control group were, respectively: 95 ± 32, 96 ± 53 and 80 ± 24 mg/dL (P = .000). Triglycerides levels in the same groups were: 116 ± 65, 112 ± 69 and 88 ± 52 mg/dL (P = .000). HDL-C levels in the 3 groups were: 52 ± 14, 53 ± 12 and 56 ± 14 mg/dL (P = .013). A significant inverse association between fruit intake and triglyceride levels in overweight participants was observed (P = .035). Fruit and vegetable intake were unusual. Conclusions: A high body mass index promotes an atherogenic lipid profile. It is necessary to implement actions to promote healthy habits associated with diet.

Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise. Fil: Quinto Sanchez, Mirsha Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Adhikari, Kaustubh. University College London; Estados Unidos Fil: Acuña Alonzo, Victor. University College London; Estados Unidos. Instituto Nacional de Antropología E Historia; México Fil: Cintas, Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Silva de Cerqueira, Caio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Ramallo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Castillo, Lucía Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Farrera, Arodi. Universidad Nacional Autónoma de México; México Fil: Jaramillo, Claudia. Universidad de Antioquia; Colombia Fil: Williams Arias. Universidad de Antioquia; Colombia Fil: Fuentes, Macarena. Universidad de Tarapacá; Chile Fil: Everardo, Paola. Instituto Nacional de Antropología E Historia; México Fil: de Avila, Francisco. Instituto Nacional de Antropología E Historia; México Fil: Gomez Valdés, Jorge. Universidad Nacional Autónoma de México; México Fil: Hünemeier, Tábita. Universidade Federal do Rio Grande do Sul; Brasil Fil: Gibbon, Shara. University College London; Estados Unidos Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú Fil: Rosique, Javier. Universidad de Antioquia; Colombia Fil: Bortolini, Maria Cátira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Canizales Quinteros, Samuel. Universidad Nacional Autónoma de México; México Fil: Rothhammer, Francisco. Universidad de Tarapacá; Chile Fil: Bedoya, Gabriel. Universidad de Antioquia; Colombia Fil: Ruiz Linares, Andres. University College London; Estados Unidos Fil: Gonzalez Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina

Background: The geographical distribution of genes plays a key role in genetic epidemiology. The Chilean population has three major stem groups (Native American, European and African). Aim: To estimate the regional rate of American, European and African admixture of the Chilean population. Subjects and Methods: Forty single nucleotide polymorphisms (SNP´s) which exhibit substantially different frequencies between Amerindian populations (ancestry-informative markers or AIM´s), were genotyped in a sample of 923 Chilean participants to estimate individual genetic ancestry. Results: The American, European and African individual average admixture estimates for the 15 Chilean Regions were relatively homogeneous and not statistically different. However, higher American components were found in northern and southern Chile and higher European components were found in central Chile. A negative correlation between African admixture and latitude was observed. On the average, American and European genetic contributions were similar and significantly higher than the African contribution. Weighted mean American, European and African genetic contributions of 44.34% ± 3 9%, 51.85% ± 5.44% and 3.81% ± 0.45%, were estimated. Fifty two percent of subjects harbor African genes. Individuals with Aymara and Mapuche surnames have an American admixture of 58.64% and 68.33%, respectively. Conclusions: Half of the Chilean population harbors African genes. Participants with Aymara and Mapuche surnames had a higher American genetic contribution than the general Chilean population. These results confirm the usefulness of surnames as a frst approximation to determine genetic ancestry.

© 2014 The Alzheimer's Association. Background A mutation in presenilin 1 (E280A) causes early-onset Alzheimer's disease. Understanding the origin of this mutation will inform medical genetics.Methods We sequenced the genomes of 102 individuals from Antioquia, Colombia. We applied identity-by-descent analysis to identify regions of common ancestry. We estimated the age of the E280A mutation and the local ancestry of the haplotype harboring this mutation.Results All affected individuals share a minimal haplotype of 1.8 Mb containing E280A. We estimate a time to most recent common ancestor of E280A of 10 (95% credible interval, 7.2-12.6) generations. We date the de novo mutation event to 15 (95% credible interval, 11-25) generations ago. We infer a western European geographic origin of the shared haplotype.Conclusions The age and geographic origin of E280A are consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century.

Introducción. La hipertensión arterial es una enfermedad multifactorial influenciada por componentes genéticos y ambientales, cuya prevalencia varía entre grupos étnicos. Se han llevado a cabo numerosos estudios en genes de sistemas reguladores de la presión arterial, como el sistema renina-angiotensinaaldosterona, el sistema nervioso simpático, los factores endoteliales, y el balance de sodio, mostrando resultados incongruentes entre poblaciones. Objetivos. Evaluar el efecto de variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 y del componente ancestral individual, sobre la hipertensión arterial y las cifras de presión arterial en una muestra de población antioqueña. Materiales y métodos. Se genotipificaron 107 casos y 253 controles para 12 variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 , y para 20 marcadores informativos de ascendencia. Se evaluó la asociación de los polimorfismos y sus interacciones, y de la composición genética ancestral con hipertensión y cifras de presión arterial. Resultados. Los genes ADD2 , rs4852706 (OR=3,0; p=0,023); DRD1 , rs686 (OR=0,38; p=0,012) y ADRB2 , rs1042718 (OR=10,0; p=0,008); y combinaciones genotípicas de DRD1 con AGTR1 ; de AGT con ADD1 ; y de ADD1 con ATP2B1 y PTGS2 , se asociaron con hipertensión arterial. El componente ancestral amerindio se asoció con disminución en la presión arterial diastólica. Conclusiones. Variantes en los genes ADD2 , DRD1 , ADRB2 , AGTR1 , AGT , ADD1 , ATP2B1 y PTGS2 , individualmente o en su interacción, se encuentran asociadas con hipertensión. El componente ancestral amerindio tiene un efecto sobre las cifras de presión arterial. Introduction: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. Objectives: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. Methods and materials: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. Results: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. Conclusion: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry., Author Summary Latin America has a history of extensive mixing between Native Americans and people arriving from Europe and Africa. As a result, individuals in the region have a highly heterogeneous genetic background and show great variation in physical appearance. Latin America offers an excellent opportunity to examine the genetic basis of the differentiation in physical appearance between Africans, Europeans and Native Americans. The region is also an advantageous setting in which to examine the interplay of genetic, physical and social factors in relation to ethnic/racial self-perception. Here we present the most extensive analysis of genetic ancestry, physical diversity and self-perception of ancestry yet conducted in Latin America. We find significant geographic variation in ancestry across the region, this variation being consistent with demographic history and census information. We show that genetic ancestry impacts many aspects of physical appearance. We observe that self-perception is highly influenced by physical appearance, and that variation in physical appearance biases self-perception of ancestry relative to genetically estimated ancestry.

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern America ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations., Facultad de Ciencias Naturales y Museo, Instituto Multidisciplinario de Biología Celular

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

Por medio del análisis de marcadores genéticos del cromosoma Y, se estudió la composición de los linajes y su distribución en los apellidos más comunes en una muestra de 471 hombres provenientes del municipio de Marinilla (Antioquia) y su zona de influencia y del municipio de Aranzazu (Caldas), y en un grupo de muestras de la población general de Medellín. Además de encontrar una tasa variable de coancestría entre apellidos y linajes del cromosoma Y, también se detectó una gran similitud en el patrón de distribución de haplogrupos/haplotipos/apellidos entre Marinilla y su zona de influencia y Aranzazu, hallazgo que refuerza la idea de la migración histórica entre estas dos regiones. Esta similitud indicaría además que en las dos poblaciones pueden circular variantes genéticas comunes vinculadas a enfermedades humanas. Using Y chromosome genetic markers we studied the lineage composition and distribution in the most common surnames in 471 males from the municipality of Marinilla and its zone of influence, the municipality of Aranzazu (department of Caldas) and a group of samples from the general population of Medellin (Antioquia). Despite a variable rate of coancestry between surnames and Y-chromosome markers, we found a high similarity in the pattern of distribution of haplogroups/haplotypes/ surnames between Marinilla and its zone of influence and Aranzazu, reinforcing the historical migration between these two regions. This similarity would indicate that in both populations may be circulating common genetic variants linked to human diseases.

La población actual del departamento del Cauca es el resultado de la mezcla de tres poblaciones parentales (europea, amerindia y africana). En este estudio se determinó la composición genética de 306 residentes del departamento mediante la utilización de 34 variantes autosómicas, 9 variantes en el cromosoma X, 6 en el ADNmt y 8 en el cromosoma Y. Los análisis de las variantes autosómicas y del cromosoma X revelaron que la población europea y la amerindia han contribuido en mayor proporción al actual acervo genético de la población estudiada. Los resultados de las variantes en el ADNmt y del cromosoma Y sugieren un fuerte sesgo sexual (flujo génico asimétrico) en el proceso de mezcla, en el que los cruces interétnicos fueron principalmente entre los colonizadores europeos y las mujeres nativas. The contemporary population of the Province of Cauca is the result of the admixture between three parental populations (European, Amerindian and African). Genetic composition was determined in 306 residents of the Province with the use of 34 autosomal markers, 9 markers in chromosome X, 6 and 8 mtDNA in chromosome Y. Autosomal and X chromosome data indicate that both European and Amerindian populations have contributed to a greater extent to the current genetic pool of the population. The mtDNA and the Y chromosome data, indicate a strong sexual bias (asymmetrical gene flow) in the admixing process, where interethnic crosses were mainly between European men and native women.

La población antioqueña posee una estructura genética compleja que refleja su historia de mezclas entre poblaciones europeas, africanas y amerindias. En este estudio se determinó la composición genética de 849 individuos de la población antioqueña, utilizando un panel de 75 marcadores informativos de ancestralidad y 4 programas que implementan métodos bayesianos para inferir la composición de la mezcla ancestral. La contribución europea (60%) fue dos veces mayor que la contribución amerindia (28%), ambas con una distribución amplia, y fue poca la contribución africana (12%). Se estimó el tiempo transcurrido desde el primer evento de mezcla, que fue de 11 generaciones por cada 100 cM, lo cual hace de esta población un recurso útil para implementar estudios de mapeo por mezcla. Se evaluó la utilidad del panel de marcadores, así como la robustez y utilidad de los diferentes programas utilizados. The genetic structure of the population of Antioquia is complex and arises from the historical admixture of European, African and Amerindian populations. The genetic makeup of 849 Antioquian individuals was determined using a set of 75 ancestry informative markers and four computer programs based on Bayesian methods in order to infer the composition of ancestral admixture. A great European component (60%) was twice as high as the Amerindian contribution (28%), both with broad distributions, followed by a smaller African contribution (12%). The average number of generations since the admixture event was 11 generations per 100 cM, which makes this population a useful resource to implement admixture mapping studies. The usefulness of the marker set as well as the power and helpfulness of the computer programs were assessed.

La sepsis, un síndrome de respuesta sistémica a la infección, es un problema de salud pública asociado a alta morbilidad y mortalidad alrededor del mundo. Entre los múltiples genes asociados a esta enfermedad se encuentra el gen que codifica para la caspasa-12 (csp-12), en el cual se ha identificado un polimorfismo de un sólo nucleótido (125T>C) en el exón 4 que predice una forma larga (L) de la proteína, que a su vez se ha asociado con riesgo de sepsis grave y alta mortalidad. Además, se ha demostrado que la frecuencia del alelo L es mucho mayor en poblaciones afroamericanas. Este estudio evalúa la presencia ó el polimorfismo 125T®C de la csp-12 en 128 individuos: 81 pacientes de Medellín con diagnóstico de sepsis, 23 individuos sanos de una población afroamericana del Chocó y 24 individuos sanos provenientes de Medellín. En las tres poblaciones se encontraron 121 individuos homocigotos S/S (csp-12 corta) y 7 heterocigotos S/L discriminados así: 3 pacientes con diagnóstico de sepsis, 3 individuos afroamericanos y 1 de la población sana de Medellín. Nuestros resultados muestran que, a pesar de ser una muestra pequeña, en nuestra población existe el alelo L, encontrándose en mayor frecuencia en individuos afroamericanos y en una menor proporción en los mestizos, tanto pacientes como en los individuos sanos. Esto indica que la población afroamericana de Colombia podría tener mayor susceptibilidad a sepsis grave que las poblaciones mestizas, las cuales, se ha demostrado, son producto de mezcla europea, amerindia y africana, ésta última en una baja proporción. Por lo tanto, se deben efectuar estudios más amplios para un mejor entendimiento de las bases genéticas de la respuesta inmune de pacientes con sepsis, con el fin de diseñar terapias más racionales y personalizadas para prevenir este síndrome. Sepsis, a syndrome of systemic response to infection is a major public health problem, because it is associated with high morbidity and mortality. Among the genes shown to be associated with this syndrome, there is one which encodes for caspase-12 (csp-12). Within this gene, the single nucleotide polymorphism 125T>C located in exon 4, which predicts a long form of the protein, has been associated with severe sepsis and increased related mortality. On the other hand, higher frequency of allele L has been reported in African American populations. The present study evaluated the csp-12 polymorphism 125T>C in 128 individuals: 81 patients with sepsis, 23 healthy African Colombian subjects and 24 healthy individuals from Medellin-Colombia. We found 121 individuals homozygous S/S (csp-12 short) in these three populations and 7 heterozygotes S/L, discriminated as follows: 3 septic patients, 3 African Colombians and 1 healthy subject from Medellin. This preliminary data suggest that the csp-12L allele is present in the Colombian population, both in African Colombians and Mestizo individuals (either septic patients or healthy individuals).Therefore, more comprehensive studies should be performed to better understand the genetic basis of the immune response of patients with sepsis in order to design more rational and personalized therapies to prevent this syndrome.

Las enfermedades complejas se caracterizan porque presentan varios genes además de factores ambientales implicados en su etiología. Las bases genéticas de la diabetes mellitus tipo 1 (T1D) supone un efecto mayor del complejo HLA que interactúa con otros genes y con el ambiente. Mucho se ha descrito acerca de la posible participación de las infecciones virales como desencadenadores de T1D. En esta revisión exploramos los posibles mecanismos por los cuales el gen RNASEH1 podría estar participando en la etiología de T1D, a partir de una infección viral. El gen RNASEH1 se localiza en la región cromosómica 2p25, la cual ha sido recientemente implicada por nosotros en la susceptibilidad a T1D. Este gen ha sido implicado en la enfermedad mediante análisis genético. Acá pretendemos dar sentido biológico a los datos genéticos. Considerando que la enfermedad es multifactorial, este planteamiento no excluye la participación de otros genes u otros factores ambientales. Complex disorders are characterized by presenting many genes and other environmental factors implicated in their etiology. The genetic bases of type 1 diabetes mellitus (T1D) suppose a major effect of the HLA complex which interacts with other genes and the environment. Much has been written about the possible implication of viral infections as triggers of T1D. This review explores the mechanisms by which the RNASEH1 gene could be involved in the etiology of T1D, due to a viral infection. The RNASEH1 gene is located in chromosome 2p25, which has been recently implicated in the susceptibility to T1D by the authors, through genetic analysis. This text hopes to establish a biological context for the genetic data. Taking into account that this is a multifactorial disease, this approach does not exclude the eventual participation of other genes or environmental factors.

Introducción. Las proteínas desacoplantes pertenecen a la familia de proteínas transportadoras de aniones que desacoplan la producción de ATP de la respiración mitocondrial, causando pérdida de protones a través de la membrana mitocondrial interna y disipando la energía en forma de calor. Aunque su función no ha sido bien establecida, algunos polimorfismos en estas proteínas se han asociado con diabetes mellitus tipo 2, obesidad y resistencia a la insulina. Objetivo. Evaluar la asociación entre las variantes -3826A/G, ID 45, -2723T/A, -1957G/A, -866G/A, -55C/T de los genes de las proteínas desacoplantes 1, 2 y 3 con diabetes mellitus tipo 2 en una población del nordeste colombiano. Materiales y métodos. Se tipificaron 545 casos y 449 controles para 14 variantes de los genes de las proteínas desacoplantes por medio de PCR y PCR-RFLP. Se hicieron pruebas de asociación simples con ji al cuadrado y se corrigieron en un análisis de regresión logística bayesiana, incluyendo los estimados de mezcla individual obtenidos mediante 54 marcadores informativos de ascendencia europea, africana y amerindia. Resultados. Las variantes -3826A (OR=0,78; IC95% 0,63-0,97; p=0,02), -55C (OR=1,41; IC95% 1,04-1,92; p=0,03) de las proteínas desacoplantes 1 y 3, respectivamente, y el haplotipo D45, -866G, -1957G, -2723T, -55C (OR=1,26; IC95% 1,02-1,56; p=0,03) se asociaron con diabetes tipo 2. Estas asociaciones se conservaron después de ajustar por la mezcla genética individual. Conclusión. Algunas variantes de las proteínas desacoplantes 1, 2 y 3, y sus haplotipos, confieren riesgo para diabetes mellitus tipo 2 en una población del nordeste colombiano. Introduction. The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance. Objective. The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus. Materials and methods. In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry. Results.Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95%CI=0.63-0.97; p=0.02) and 55C (OR=1.41; 95%CI=1.04-1.92; p=0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR=1.26; 95%CI=1.02-1.56; p=0.03) were found. These associations remained after adjustment using individual genetic admixture estimates. Conclusion.Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.

Introducción. La mutación E280A en el gen de presenilina 1 se encuentra asociada al grupo familiar más grande del mundo con enfermedad de Alzheimer. La presenilina 1 es un componente esencial del complejo g-secretasa, responsable de la producción del péptido beta -amiloide, considerado clave en la fisiopatogenia de la enfermedad. Objetivo. Determinar si la mutación E280A en presenilina 1 incrementa la producción de b-amiloide, como reflejo de la ganancia de función gamma -secretasa. Materiales y métodos. Se evaluaron, por la tinción con rojo congo e inmunohistoquímica, depósitos sistémicos de b-amiloide en tejidos de cadáveres afectados, portadores de la mutación E280A en la presenilina 1 y cadáveres de no afectados. Se cuantificó por la técnica de ELISA el beta -amiloide de 40 y 42 aminoácidos en cultivos de células CHO que expresan la proteína precursora de amiloide, transfectadas con los cADN de presenilina 1 portando las mutaciones M146L, E280A, D E9 y L392V. Resultados. Se encontraron depósitos proteicos en todos los tejidos estudiados y escasos depósitos de beta -amiloide. No se encontró diferencia en la cantidad de depósitos, ni en su localización. No se observó incremento en la producción de beta -amiloide en las células transfectadas con los cADN de presenilina 1 con las mutaciones comparadas con los controles. Conclusiones. La mutación E280A en presenilina 1 no aumentó la producción de beta -amiloide en tejidos periféricos no neuronales o en el modelo in vitro, contrario a lo que sucede en una ganancia de función de gamma -secretasa. Introduction. The E280A mutation of the presenilin 1 gene has been found to be the most common associate in Alzheimer’s patients with a family history of this disease. Presenilin 1 is a critical component of the g-secretase complex and plays an essential role in the production of amyloid-beta peptide. This peptide has been strongly associated with the physiopathology of the disease. Objective. The E280A mutation in the presenilin 1 was investigated for increased production of amyloid-beta , as a response to gain in gamma-secretase function. Materials and methods. Levels of systemic amyloid-beta were measured with congo red staining and immuno-histochemistry of the tissues of affected cadavers, compared with non-affected cadavers. The 40 and 42 amino acid amyloid-beta levels were quantified by ELISA assay in CHO cell cultures. The amyloid precursor protein expressed by the cultures was detected by transfection with the cDNAs of presenilin 1 carrying the M146L, E280A, DE9 y L392V mutations. Results. Protein deposits were found in all tissues investigatged, but only a few with beta -amyloid deposition. No differences were observed in the amount or location of amyloid-beta between affected and unaffected cadavers. Not increase was noted in the production of amyloid-beta from the CHO cells transfected with cDNA from any of the mutations of presenilin 1. Conclusions. The E280A mutation in the presenilin 1 gene was not associated with the increased production of amyloid-beta in non-neuronal peripheral tissues, or in the in vitro model. This is in contrast to the expectation in a gamma-secretase gain of function.

Introducción. La utilización de la frecuencia de apellidos como marcadores de linajes paternos ha permitido caracterizar poblaciones. Los principios de isonimia se han empleado para determinar el grado de estructuración genética, las tasas de migraciones y las relaciones de ancestría y origen entre poblaciones. Este análisis se aplicó a dos poblaciones históricamente relacionadas y consideradas como aislados genéticos. Objetivo. Evaluar las relaciones genéticas y de origen entre Aranzazu y Marinilla y su zona de influencia por medio de análisis de frecuencia de apellidos. Materiales y métodos. A partir de la base de datos del Sistema de Identificación de Beneficiarios de los Programas Sociales, Sisbén, se calcularon los parámetros poblacionales de coeficiente de parentesco (fiii), la homogeneidad poblacional con los estimadores B (porcentaje de la población que comparte los siete apellidos más frecuentes) y C (15 apellidos más frecuentes) y la distancia genética de Cavalli-Sforza en tres poblaciones del núcleo fundador de Marinilla y Rionegro como población externa. Resultados. Marinilla y Aranzazu, al igual que las poblaciones de Marinilla y su zona de influencia, mostraron los mayores valores de homogeneidad (valores B entre 0,25 y 0,5) comparados con Rionegro (B = 0,159) y también mayores valores de parentesco intrapoblacional (valores fiii entre 0,0034 y 0,01). Las menores distancias se encontraron entre Marinilla y Aranzazu. Conclusiones. Aranzazu es una población con características similares a las de Marinilla y su zona de influencia y debido al efecto fundador, estas poblaciones pueden presentar características genéticas similares. Por lo tanto, las enfermedades genéticas, principalmente las de herencia compleja, podrían tener la misma etiología genética en ambas poblaciones, lo que garantizaría las condiciones óptimas para estudios de cartografía genética. Introduction. Surname frequency (isonymy) is used as a marker of paternal lineage and is used to characterize human population structure. Principles of isonymy were used to determine the genetic structure, migration rates, ancestry relations and origins of populations. This analysis was applied to two historically related local populations which currently are considered to be genetically isolated. Objective. The genetic relationships and influence zones of the Aranzazu and Marinilla populations were assessed by means of surname frequency analysis. Materials and methods. Data originated from database with the title "System of Identification of Beneficiaries of the Social Programs" database or Sisben. Population parameters such as a priori kinship (phiii), population homogeneity with B and C estimators, and Cavalli-Sforza’s genetic distance were calculated for (a) three towns of Marinilla and its influence zone and (b) Aranzazu. The Rionegro population served as an external, comparison population. Results. The Aranzazu and Marinilla populations showed the higher homogeneity (B value between 0.25 and 0.5) in contrast with Rionegro (B = 0.159), as well as greater a priori kinship values (phiii between 0.003 and 0.010). The lowest distances were found between Marinilla and Aranzazu. Conclusions. Aranzazu is a population with characteristics similar to those of Marinilla and its influence zone. The close similarity of genetic characteristics for these populations is due probably to a founder effect. Furthermore, the genetic similarity predicts that genetic diseases will have the same etiology in both populations and provides optimum conditions for gene mapping studies.

Objetivo: validar la entrevista diagnóstica para estudios genéticos (DIGS 3.0) en Colombia. Métodos: se hicieron dos traducciones del inglés al español del DIGS y se hizo traducción en sentido inverso (al inglés) de cada una. Un comité de revisión verificó la equivalencia translingüística y transcultural. Se evaluó la confiabilidad examen-reexamen e interevaluador del DIGS 3.0 en 65 y 91 pacientes, respectivamente, mediante el cálculo de kappa de Cohen. Resultados: el DIGS 3.0 mostró ser comprensible, con validez de apariencia y de contenido. La confiabilidad interevaluador fue excelente para esquizofrenia (kapa=0,81, IC95%: 0,68-0,93), trastorno bipolar (kapa=0,87, IC95%: 0,75-0,99), trastorno depresivo mayor (kapa=0,86, IC95%: 0,7- 1) y ausencia de trastorno psiquiátrico (kapa=0,88, IC95%: 0,71-1); fue buena para otro diagnóstico psiquiátrico (kapa=0,65, IC95%: 0,41-0,89) y pobre para trastorno esquizoafectivo (kapa=0,37, IC95%: -0,02-0,76). La confiabilidad examen-reexamen fue excelente para todos los diagnósticos (kapa>0,8), excepto para otro diagnóstico psiquiátrico (kapa=0,64, IC95%: 0,31-0,96), donde fue buena. Conclusiones: la versión en español del DIGS para Colombia mostró comprensibilidad, validez de apariencia y de contenido, y confiabilidad examen-reexamen e interevaluador. Es una herramienta útil para estudios genéticos en esquizofrenia y en trastornos afectivos. An interview tool, Diagnostic Interview for Genetic Studies (DIGS 3.0), was translated into Spanish for application in studies of psychiatric disorders in Colombia. Two Spanish translations of the original English version of DIGS were prepared and backtranslated into English. A review committee verified the linguistic and cultural equivalence of the translations. The evaluator and test-retest reliability were assessed calculating Cohen’s kappa for samples of 65 and 91 patients respectively. DIGS proved valid in both appearance and content. The confidence interval (C.I.) was excellent for schizophrenia (kappa=0.81, C.I. 95% = 0.68-0.93), bipolar disorder (kappa=0.87, C.I. 95% = 0.75-0.99), major depressive disorder (kappa=0.86, C.I. 95% = 0.70-1.00), and for a normal diagnosis (kappa=0.65, C.I. 95% = 0.41-0.89); it was good for other psychiatric diagnosis (kappa=0.65, C.I. 95% = 0.41-0.89) and poor for schizoaffective disorder (kappa=0.37, C.I. 95% = -0.02-0.76). Test-retest reliability was excellent for all diagnoses (kappa>0.8), except for "other psychiatric diagnoses" (kappa=0.64, C.I. 95% = 0.31-0.96). The Spanish translation of the DIGS was comprehensible, with face and content validity, and good test-retest and evaluator reliability. This translation will be a useful tool for genetic studies of psychiatric disorders in Latin America, particularly where schizophrenia and affective disorders are involved.

LA DIABETES MELLITUS (DM) comprende un grupo heterogéneo de desordenes hiperglucémicos clasificados en subgrupos de acuerdo a su fisiopatología y etiología, entre los cuales se destacan la Diabetes Mellitus tipo1 (DM1) y la diabetes mellitus tipo 2 (DM2). La DM1 es de aparición temprana y una absoluta escasez de insulina hace que los pacientes sean insulino dependientes desde el inicio de los síntomas y la (DM2), de inicio en la edad adulta y no todos los pacientes que la sufren son insulino dependientes. La DM1 se clasifica como DM1A si es el efecto de una respuesta autoinmune por parte de las células del páncreas y DM1B si la causa es desconocida (idiopática). Los estudios sobre la etiología de DM1 han demostrado que ambos subtipos tienen un fuerte componente genético, pero el patrón de herencia es complejo, ya que su patogénesis puede ser el resultado de la interacción de variantes en múltiples genes con factores medioambientales. Los estudios genéticos sobre DM1 han permitido identificar loci de suceptibilidad que se denominan IDDM, así para DM1A se encontró el primer locus (IDDM1) en la región HLA-DR/DQ, situada en 6p21, que modula el efecto de otros genes implicados en la enfermedad, el segundo (IDDM2) se localiza en 11p15 donde se encuentra el gen de la Insulina. Es decir, DM1 presenta gran heterogeneidad genética, de tal manera, que se han identificado más de 18 loci implicados en susceptibilidad a ella, entre ellos 3 en el cromosoma 2 (IDDM 7,12 y 13) y uno en el cromosoma 14 (IDDM11), este último asociado a DM1B. El objetivo de este estudio consistió en la búsqueda de loci en los cromosomas 2 y 11 involucrados en la susceptibilidad a DM, en 3 familias antioqueñas, para lo cual se realizó análisis de ligamiento paramétrico a 23 marcadores microsatélites en el cromosoma 2 y a 18 en el cromosoma 11. A las familias, codificadas como DM1(11afectados), familia 1 (2 afectados) y familia10 (3 afectados), se les realizó simulación para determinar el poder para hacer análisis de ligamiento y los resultados mostraron que presentaban suficiente poder para realizarlo, puesto que en DM1 la razón de disparidad máxima (Lod score o Z máximo) fue de 3.57, sin recombinación (θ=0), el cual es superior a 3, el valor aceptado para determinar ligamiento, y al tomar las tres familias en conjunto se obtuvo un Z máximo de 5.76. Con el análisis de ligamiento para el cromosoma 11, se halló que solo en la familia 10 se presentaba un valor positivo de Z; 1.18 al marcador D11S925 con ?=0, muy superior al de la simulación de esta familia (0.75), con respecto al cromosoma 2, se obtuvieron valores de Z positivos al marcador D2S319 en DM1 y familia 10, 2.08 y 0.88 respectivamente, con θ=0. Al tomar las tres familias como un todo y calcular Z para los marcadores D11S925 y D2S319, se obtuvo un valor de 2.5, con θ=0, lo cual está corroborando que en las familias analizadas están involucrados 2 loci, situados en las regiones de los cromosomas 11 y 2 señaladas por dichos marcadores. Si se tiene en cuenta que el marcador D11S925 está situado en la región 11q23-3 y el D2S319 en la 2qter, se puede decir, que con este trabajo se han identificado 2 loci nuevos de susceptibilidad a DM1 en la población antioqueña, ya que estas regiones no concuerdan con las reportadas hasta el presente; además, como se hizo análisis de ligamiento a IDDM1, con resultados negativos (datos no mostrados), la DM1 estudiada podría clasificarse como DM1B. DIABETES MELLITUS (DM) comprises e heterogeneous group of hypoglycemic disorders, that are grouped according to their physiopathology and etiology; the most notorious ones are type 1 DM (DM1) and type 2 DM (DM2); DM1 is characterized by early onset and absolute lack of insulin; therefore, patients suffering from it depend on insulin since the beginning of their symptoms; in contrast, DM2 manifests during adult life and not all patients depend on insulin. DM1 is classified as DM1A when it results from an autoimmune response of pancreatic b cells, and DM1B if it is of unknown origin (idiopathic). Studies on the etiology of DM1 have revealed that both types have a strong genetic component but their inheritance pattern is complex since its pathogenesis may result from the interaction with environmental factors of variants in multiple genes. By means of genetic studies on DM1, susceptibility loci known as IDDM have been identified, namely: for DM1A the first locus (IDDM1) was found in the HLA-DR/QD region, located in 6p21, that modulates the effect of other genes involved in the disease; the second one (IDDM2) is located in 11p15, the site of the insulin gene. That means, DM1 exhibits wide genetic heterogeneity so that more than 18 loci involved in susceptibility to this disease have been identified, among them, 3 on chromosome 2 (IDDM 7, 12, and 13), and 1on chromosome 14 (IDDM11), the latter being associated to DM1B. The aim of this study was the search for loci on chromosomes 2 and 11 involved in the susceptibility to DM, in three families from Antioquia, Colombia; for that purpose, parametric linkage analysis was performed to 23 microsatellite markers on chromosome 2, and to 18 on chromosome 11. In order to determine the power for making linkage analysis, simulation was carried out on the families, coded as DM1 (11 affected members), family 1 (2 affected members), and family 10 (3 affected members); results demonstrated power enough for that purpose since in DM1 the maximum odds ratio (Lod score or Z maximum) was 3.57 without recombination (=0=0), above 3, the accepted value for determining linkage; when the three families were taken together, a maximum Z of 5.76 was obtained. With the linkage analysis for chromosome 11, it was found that only in family 10 there was a positive Z value, 1.18 to marker D11S925 with =0=0, above the simulation value for this family (0.75); as regards chromosome 2, positive Z values were obtained to marker D2S319 in DM1 and family 10: 2.08 and 0.88, respectively, with =0=0. When the three families were taken as a whole and Z values were calculated for markers D11S925 and D2S319, a value of 2.5 was obtained, with =0=0, which confirms that in the analysed families 2 loci are involved, located in the regions of chromosomes 11 and 2 signaled by such markers. If it is taken into account that the D1S925 marker is located in the region 11q23-3, and the D2S319 marker, in the region 2qter, it may be said that in this work two new loci of susceptibility to DM1 have been identified in three families from Antioquia, Colombia, since these regions do not agree with those so far reported; besides, since results were negative in linkage analysis to IDDM1(data not shown), the studied cases of DM1 could be classified as DM1B.

It has been proposed that women had a higher migration rate than men throughout human evolutionary history. However, in a recent study of South American natives using mtDNA restriction fragment polymorphisms and Y-chromosome microsatellites we failed to detect a significant difference in estimates of migration rates between the sexes. As the high mutation rate of microsatellites might affect estimates of population structure, we now examine biallelic polymorphisms in both mtDNA and the Y-chromosome. Analyses of these markers in Amerinds from North, Central and South America agree with our previous findings in not supporting a higher migration rate for women in these populations. Furthermore, they underline the importance of genetic drift in the evolution of Amerinds and suggest the existence of a North to South gradient of increasing drift in the Americas.

Una de las posibles causas de la PGR es la trombofilia, lacual se define como una tendencia a desarrollar trombosis convariabilidad en las manifestaciones clínicas dependiente de laregión vascular afectada por la ausencia del flujo sanguíneo. Latrombosis es una enfermedad multifactorial, en la cualcontribuyen factores genéticos y ambientales al riesgo deldesarrollo de la enfermedad (1). Las trombofilias heredadas están asociadas a polimorfismos en los genes del factor V LeidenG1691A, protrombina G20210A y ilentetrahidrofolatoreductasa(MTHFR) C677T; también se asocia a las deficiencias de los niveles de antitrombina III (AT-III), proteína C (PC) y proteínaS (PS) en el sistema vascular y a la resistencia a la proteína Cactivada (RPCa). Varios estudios han encontrado asociación delas trombofilias heredadas con PGR y trombosis venosa asociadaal embarazo (2), aunque los mecanismos fisiopatológicos responsables de las patologías vasculares placentarias en mujeres con trombofilia aun no han sido esclarecidos (3).El objetivo de este estudio es establecer la asociación de lastrombofilias heredadas G1691A, G20210A, C677T, lasdeficiencias de AT-III, PC. PS y la RPCa, con la pérdida gestacional recurrente.

No ha de llamar la atención de los médicos estudiosos, las complicaciones variadas que los enfermos carriónicos sufren durante el desarrollo de su enfermedad que, como sabemos, pueden tener lugar aún en el periodo de convalecencia, dado que la Verruga Peruana produce anergia. Los investigadores peruanos, desde la época en que inquieto el estudio de la llamada, entonces, Fiebre de la Oroya, tuvieron siempre todo empeño por estudiar la naturaleza de las infecciones agregadas que han sido, acaso, las que mataban a los enfermos de Verruga.

We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians-signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas.