David Celorrio

Y-STR variation in the Basque diaspora in the Western USA: evolutionary and forensic perspectives

Individuals of Basque origin migrated in large numbers to the Western USA in the second half of the nineteenth century, and the flow continued with less intensity during the last century. The European source population, that of the Basque Country, has long been a cultural and geographical isolate. Previous studies have demonstrated that Y-STR frequencies of Basques are different from those of other Spanish and European populations [1]. The Basque diaspora in the Western USA is a recent migration, but the founder effect and the incorporation of new American Y chromosomes into the paternal genetic pool of the Basque diaspora could have influenced its genetic structure and could thus have practical implications for forensic genetics. To check for genetic substructure among the European source and Basque diaspora populations and determine the most suitable population database for the Basque diaspora in the Western USA, we have analysed the haplotype distribution of 17 Y-STRs in both populations. We have found that the Basque diaspora in the Western USA largely conserve the Y chromosome lineage characteristic of the autochthonous European Basque population with no statistically significant differences. This implies that a common 17 Y-STR Basque population database could be used to calculate identification or kinship parameters regardless of whether the Basque individuals are from the European Basque Country or from the Basque diaspora in the Western USA.

Association of alcohol dehydrogenase polymorphisms and life-style factors with excessive alcohol intake within the Spanish population (EPIC-Spain).

AIMS To analyse associations between alcohol dehydrogenase (ADH) polymorphisms and alcohol intake in Spanish men and women. DESIGN AND SETTINGS We analysed the relationship between 21 genetic variants in ADH genes and excessive alcohol intake in both men and women. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array and a sex-stratified analysis was performed. MEASUREMENTS Ethanol intake was calculated using a validated dietary history questionnaire. PARTICIPANTS Heavy consumers of alcohol (≥70 g/day in men, ≥42 g/day in women) (653 cases) and very low or non-consumers (<2 g/day) (880 controls) from the Spanish cohort of the European Prospective Investigation into Cancer (EPIC). FINDINGS We found statistically significant associations between alcohol intake and known life-style factors; namely, smoking and food energy intake (meat and fruit/seeds) in both men and women, as well as with physical activity in women and educational level in men. Additionally, we found that a non-synonymous coding SNP in ADH1B (rs1229984) is associated inversely with excessive alcohol intake in men [odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.11-0.33; P = 4.77E(-10) ) and women (OR = 0.48, 95% CI = 0.27-0.83; P = 0.0067). Furthermore, ADH6 rs3857224 was found associated with heavy alcohol intake in women (OR = 1.61, 95% CI = 1.21-2.14; P = 1.01E(-3) ), but not in men. CONCLUSIONS In the Spanish population, the single nucleotide polymorphism of alcohol dehydrogenase ADH1B, rs1229984, is associated inversely with alcohol intake in both men and women. Another polymorphism of ADH6, rs3857224, is associated with heavy alcohol intake in women.

Alcohol-Metabolizing Enzyme Gene Polymorphisms in the Basque Country, Morocco, and Ecuador

BACKGROUND Genes ADH1B and ADH1C have certain functional SNPs that are related to alcoholism. The frequencies of these polymorphisms vary between populations, so studying them in populations made up of groups with different phylogeographic origins requires an individualized analysis of each group. In the Basque Country, various recently arrived foreign groups live side by side with the original Southern European population, particularly North Africans from Morocco and Hispanics from Ecuador. This study sets out to examine the distribution of the frequencies of alleles that encode alcohol dehydrogenase with different metabolization rates, as higher rates make for greater susceptibility to alcoholism. METHODS Four SNPs: rs1229984, rs2066702, rs698, and rs1693482 using Taqman technology with a Rt-PCR were studied in a sample of 114 European individuals originating from the Basque Country, 100 North Africans from Morocco, and 109 Hispanics from Ecuador. The allele and genotype frequencies were calculated using Genepop v4.0. The most frequent haplotypes were estimated using the ELB algorithm with Arlequin v3.01. A breakdown of the complete disequilibrium commonly observed between the 2 missense polymorphisms that distinguish the common ADH1C alleles rs698 and rs1693482 was observed and confirmed by sequencing in 2 individuals from the Basque Country. RESULTS A higher frequency of protective allele ADH1C*1 was found in the North African population group. Haplotype combinations are also studied, and the rare association of alleles ADH1B*2-ADH1C*2 was observed in the Southern European group in the Basque Country, along with an allele not hitherto described in the ADH1C locus. CONCLUSIONS This study provides the first data published on the allele and genotype frequencies of the ADH1C locus in the Moroccan population and on the ADH1B and ADH1C loci in the Ecuadorian population. The study shows differences in the distribution of the frequency of allele ADH1C*1 between the Basque Country and Moroccan populations, and a new allele not described to date.

I-DNASE21 system: development and SWGDAM validation of a new STR 21-plex reaction.

I-DNASE21 is a new STR multiplex system that amplifies 21 STR autosomal loci, plus the amelogenin locus in one reaction. This system has been designed to analyze all the STR loci included in the Combined DNA Index System (CODIS), Interpol Standard Set of Loci (ISSL), Extended European Standard Set (ESS-Extended), UK National Criminal Intelligence DNA Database (NDNAD) and German Core loci (GCL). This manuscript presents the validation of the I-DNASE21 system according to the revised guidelines issued by the Scientific Working Group on DNA Analysis Methods (SWGDAM). The results of this validation, added to the extremely high discriminatory power showed, suggest that I-DNASE21 could be a potentially helpful tool for identification and kinship determination even in complex paternity cases.

A comparison of Val81Met and other polymorphisms of alcohol metabolising genes in patients and controls in Northern Spain

The aim of this paper is to study polymorphism in the TH, ADH1B, ADH1C, ALDH2 and CYP2E1 genes so as to ascertain whether it is associated with excessive consumption of alcohol. The SNPs rs6356 of TH, rs1229984, rs2066702 of ADH1B; rs698, rs1693482 of ADH1C; rs671 of ALDH2; rs72559710, rs55897648, rs6413419, rs3813867, rs2031920, rs6413432 of CYP2E1 were studied in a sample of 172 high-level patients and 150 fully non-drinkers controls. Genotyping was performed using Rt-PCR with Taqman probes. SNPs located at ALDH2 and CYP2E1 showed no heterozygosity. Frequency distribution showed significant differences between the two groups studied for loci TH and ADH1B. The genotype Val/Val of TH locus increased in risk 1.988 times (95% CI: 1.006-3.930) that the subjects carrying the genotype Met/Met; and the genotype ADH1B*1/*1 of ADH1B locus increased in risk 3.811 times (CI: 1.660-8.749) that the subjects carrying the genotype ADH1B*1/*2. Alleles Val and ADH1B*1 may therefore increase the risk of the onset and development of this illness.

Influence of Dopaminergic System Genetic Variation and Lifestyle Factors on Excessive Alcohol Consumption

AIMS To examine the role of genetic and environmental factors in the pathogenesis of alcohol dependence in a Spanish cohort of women and men. METHODS We analyzed the relationship between 56 genetic variants in 7 genes associated with the dopaminergic reward pathway and excessive alcohol consumption. The study sample (N = 1533, of which 746 were women) consisted of 653 heavy consumers and 880 very low consumers from the Spanish subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. Lifestyle variables were also examined to assess associations between genetic and environmental factors. RESULTS No statistically significant differences were found between cases and controls for the allele frequencies in five genes: TH, SLC18A2, DRD1, DRD3 and COMT. Conversely, some alleles of the 12 SNPs from the DRD2 locus and the 5 from the MAOA locus showed significant associations with excessive alcohol consumption. Namely, rs10891556 (DRD2) proved to be the only SNP positively correlated with excessive alcohol consumption in both sexes. DRD2 rs1800497 and rs877138 were significantly associated in men, whereas DRD2 rs17601612 and rs4936271 and MAOA rs5906898 were associated with excessive alcohol consumption in women. A correspondence analysis provided an overall lifestyle profile of excessive drinkers, who were predominantly men who smoked, had large intakes of meat, small intakes of fruit and vegetables, whose jobs did not require high education levels and who engaged in little physical activity. CONCLUSIONS It has shown the influence of dopaminergic pathway in the genetics of alcohol dependence with differences between men and women and providing a lifestyle profile of excessive drinkers.