Los marcadores informativos de ancestralidad (AIM) autosómicos y los del ADN mitocondrial (ADNmt) son muy útiles para identificar el origen y los patrones de migración de las poblaciones. En este ...trabajo se estimó el mestizaje a partir de siete AIM en 188 individuos venezolanos, 84 del estado Guárico y 104 de la región centro occidental de Venezuela (RCO), se estimó la ancestralidad mitocondrial en el estado Guárico y se compararon ambas poblaciones según su origen y desarrollo histórico. Este estudio representa la primera aproximación a la composición genética de Guárico y es el primer reporte para Venezuela utilizando marcadores tipo AIM. Los resultados revelaron que los aportes amerindio y europeo predominan en estas poblaciones, pero el amerindio es mayor en Guárico (50,57 %) que en RCO (44,92 %), y el europeo lo es en RCO (38,46 % vs. 33,72 %). El origen del ADNmt en Guárico es de predominio amerindio (80 %), tendencia similar a lo reportado para RCO (75 %). El aporte amerindio en Guárico es el más alto reportado para Venezuela. Se concluye que las diferencias encontradas entre ambas muestras podrían deberse a la colonización más temprana de la RCO y a su desarrollo industrial moderado durante el siglo XIX. Así mismo, planteamos que los AIM aquí utilizados lograron una buena discriminación del aporte de los tres grupos ancestrales principales y que su uso simultáneo con polimorfismos de origen uniparental permite obtener, en forma económica, una mejor aproximación genética para explicar la dinámica del proceso de mestizaje que dio origen a la población venezolana actual.
Background: Polymorphisms with decreased enzyme activity of their gene products have been reported in region CYP2C with population variations in haplotype structure.
Aim: To estimate the allelic and ...genotypic frequencies of variants CYP2C9*2 and CYP2C9*3 and of CYP2C9/CYP2C19 haplotypes in Venezuelan populations.
Subjects and methods: Six hundred and thirty-four individuals from nine admixed populations (AP) and the Warao indigenous group were studied. Allelic frequencies, linkage disequilibrium and genetic distances for haplotypes were calculated and compared within Venezuela and with data available in the literature.
Results: Heterogeneity in the distribution of CYP2C9 alleles and CYP2C9/CYP2C19 haplotypes among the AP and the Warao was observed. The joint frequency of haplotypes, with at least one non-functional variant, shows values in AP between 21-41%, while in Warao it reaches 5%. The haplotype that includes the Asian and rare Latin America CYP2C19*3 allele was detected in most AP and in Warao. Pairwise Fst values showed that the Warao was an outlier compared with the AP, while these are closer to European-derived populations. No significant correlation was found between haplotype frequencies and admixture.
Conclusions: These results support the need to understand the distribution of genomic biomarkers related to the metabolism of drugs, for planning national public health strategies.
The present Venezuelan population is the product of admixture of Amerindians, Europeans, and Africans, a process that was not homogeneous throughout the country. Blood groups, short tandem repeats ...(STRs), mtDNA, and Y-chromosome markers have been used successfully in admixture studies, but few such studies have been conducted in Venezuela. In this study we aim to estimate the admixture components of samples from two different socio -economic levels from Caracas, Venezuela's capital city, compare their differences, and infer sexual asymmetry in the European Amerindian union patterns. Gene frequencies for blood groups ABO and Rh (CDE) and for the STRs VWA, F13A01, and FES/FPS and mtDNA and Y-chromosome haplogroups were studied in a sample of 60 individuals living in Caracas, taken from a private clinic (high socioeconomic level), and 50 individuals, also living in Caracas, drawn from a public maternity clinic (low socioeconomic level). The admixture analysis for the five autosomal markers gives a high European component (0.78) and an almost negligible African sub-Saharan component (0.06) for the high socioeconomic level, whereas for the low socioeconomic level the sub-Saharan, European, and Amerindian components were 0.21, 0.42, and 0.36, respectively. Estimates of admixture based on mtDNA and Y-chromosome markers reveal that the Amerindian contribution to these Caracas samples is almost entirely through females, because the Y-chromosome Amerindian and African sub-Saharan chromosomes found in this study were scarce. Our study reveals that the identification of the grandparents' geographic origin is an important methodological aspect to take into account in genetic studies related to the reconstruction of historical events.
Abstract Introduction The single nucleotide polymorphism Val35Leu has been described within the A subunit of gene Factor XIII (FXIII-A) in association with an increase of FXIII activity. In the ...gene's promoter region STR F13A01 is present, however there is no available data related about its influence on the expression of FXIII. Materials and Methods Blood samples were obtained from apparently healthy and unrelated biologically individuals from northeastern area of Venezuela. The system Val35Leu was amplified by PCR-RFLP using Mse I as restriction enzyme. FXIIIA and FXIIIB levels were measured by rocket- immunoelectrophoresis. FXIII activity was measured with a Berichrom kit and fibrinogen by clot weigh method. Results FXIII-A had an activity range between 50–184% and FXIII-B between 50–155%. FXIII activity had a range of 59–147%. Fibrinogen was found between 122–502 mg/dL. None of these values showed association with Val35Leu genotypes. In the third fibrinogen tertile a higher FXIII activity was found (96 ± 24%) and a higher frequency of Leu/Leu genotype (7.02%). A significant correlation between fibrinogen and FXIII activity (r = 0.2706, p > 0.01) was observed. Nine different alleles were detected in the STR polymorphism, with the most frequent alleles being 7 (24.70%), 6 (15.06%), 5 (22.29%), 4 (18.07%), and 3.2 (13.25). The results suggest an increase in FXIII activity as the number of repetitions in F13A01 increased up to allele 5. Conclusions This study offers new genetic information of FXIII activity and levels reference values from Venezuelan human population.
Large differences in relation to dental size, number, and morphology among and within modern human populations and between modern humans and other primate species have been observed. Molecular ...studies have demonstrated that tooth development is under strict genetic control, but, the genetic basis of primate tooth variation remains unknown. The PAX9 gene, which codes for a paired domain-containing transcription factor that plays an essential role in the development of mammal dentition, has been associated with selective tooth agenesis in humans and mice, which mainly involves the posterior teeth. To determine whether this gene is polymorphic in humans, we sequenced ≈2.1 kb of the entire four-exon region (exons 1, 2, 3 and 4; 1,026 bp) and exon-intron (1.1 kb) boundaries of 86 individuals sampled from Asian, European, and Native American populations. We provided evidence that human PAX9 polymorphisms are limited to exon 3 only and furnished details about the distribution of a mutation there in 350 Polish subjects. To investigate the pattern of selective pressure on exon 3, we sequenced ortholog regions of this exon in four species of New World monkeys and one gorilla. In addition, orthologous sequences of PAX9 available in public databases were also analyzed. Although several differences were identified between humans and other species, our findings support the view that strong purifying selection is acting on PAX9. New World and Old World primate lineages may, however, have different degrees of restriction for changes in this DNA region.
Mitocondrial DNA (mtDNA) has been widely used to study genetic relationships between contemporary Amerindian groups and to infer ancestral migration movements; however inferences about migration ...routes of prehispanic extinct groups are difficult. Admixture of Neoamerican groups has been characterized by unions between European males and Amerindian females. This allows the identification in present populations of Amerindian mitocondrial haplogroups which give information on ancestral groups. In order to investigate female lineages present in western Venezuela, RFLP haplogroups from mtDNA were obtained from 193 individuals with grandparents from this region, 81 from the State of Lara (Barquisimeto) and 112 from 3 towns of the State of Falcon (Macuquita=25; Macanilla=29 and Churuguara=58). Comparison of haplogroup distributions between groups was performed, and admixture estimates based on female lineages were obtained. The distribution of four Amerindian haplogroups was compared with those of other populations from the American Continent. In our four samples Amerindian haplogroups predominate, followed by those of African origin. In the comparison of the mtDNA Amerindian fraction with other populations we find that Macanillas, Lara and Churuguara are similar to South American and Amazonian groups whilst Macuquita is similar to groups from Aruba. Our findings suggest an important genetic diversity in this region, explained by migration routes to and from the south and the Caribean. They also suggest genetic relationship between prehispanic groups from Aruba and those from the Paraguaná peninsula, which have been inferred by archeological evidences. An increase in sample size and analysis of sequences for more precision is recommended.
Pharmacogenetics and Pharmacogenomics areas are currently emerging fields focused to manage pharmacotherapy that may prevent undertreatment while avoiding associated drug toxicity in patients. Large ...international differences in the awareness and in the use of pharmacogenomic testing are presumed, but not well assessed to date. In the present study we review the awareness of Latin American scientific community about pharmacogenomic testing and the perceived barriers for their clinical application. In order to that, we have compiled information from 9 countries of the region using a structured survey which is compared with surveys previously performed in USA and Spain. The most relevant group of barriers was related to the need for clear guidelines for the use of pharmacogenomics in clinical practice, followed by insufficient awareness about pharmacogenomics among clinicians and the absence of regulatory institutions that facilitate the use of pharmacogenetic tests. The higher ranked pairs were TPMT/thioguanine, TPMT/azathioprine, CYP2C9/warfarin, UGT1A1/irinotecan, CYP2D6/amitriptiline, CYP2C19/citalopram and CYP2D6/clozapine. The lower ranked pairs were SLCO1B1/simvastatin, CYP2D6/metoprolol and GP6D/chloroquine. Compared with USA and Spanish surveys, 25 pairs were of lower importance for Latin American respondents. Only CYP2C19/esomeprazole, CYP2C19/omeprazole, CYP2C19/celecoxib and G6PD/dapsone were ranked higher or similarly to the USA and Spanish surveys. Integration of pharmacogenomics in clinical practice needs training of healthcare professionals and citizens, but in addition legal and regulatory guidelines and safeguards will be needed. We propose that the approach offered by pharmacogenomics should be incorporated into the decision-making plans in Latin America.
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