Manel Gené

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk.

Objectives: The human GSTTP1 gene is polymorphic with an A → G transition in exon 5 causing a replacement 105 Ile→Val in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.

Major Mitochondrial DNA Haplotype Heterogeneity in Highland and Lowland Amerindian Populations from Bolivia

This study provides the frequencies of four mitochondrial DNA (mtDNA) haplogroups of 233 native South Amerindians in eight populations living in the Beni Department of Bolivia, including six populations not previously studied. Linguistically, these populations belong to the three principal South Amerindian language stocks, Andean, Equatorial-Tucanoan, and Ge-Pano-Carib. Frequency analyses under geographic, historic, linguistic, and genetic configurations using the statistic of Weir (Weir 1990) and analysis of molecular variance (AMOVA) show similar results. Results are also similar when phenetic cluster is used. Aymara belongs almost exclusively to haplogroup B, Quechua- and Moseten-speaking tribes belong to haplogroups A and B, but the first tribe presents high frequencies of haplogroup B. Yuracare, Trinitario, and Ignaciano exhibit high frequencies of A, B, and C haplogroups, and the Movima present a large proportion of haplogroup C. There is some correspondence between mtDNA haplogroup frequencies and language affiliation and historical connections, but less so with geographic aspects. The present study provides a context for understanding the relationship between different Amerindian populations living in a multiethnic area of Bolivia.

Mitochondrial DNA diversity in the Llanos de Moxos: Moxo, Movima and Yuracare Amerindian populations from Bolivia lowlands

Background: Movima, Yuracare, Ignaciano and Trinitario are Amerindian populations living in the Bolivian lowlands of the Amazonian basin. The cultural and genetic affinity of the peoples living in this area is poorly known, despite many archaeological studies demonstrating its importance in pre-Columbian times. Densely populated Amerindian groups occupied the region, both in the Llanos and along the river streams of the Amazonian basin, practising intense agricultural activities and exchange of goods. The historical and linguistic records indicate that the land was occupied through successive migrations that gave rise to complex socio-economic communities. Genetic information suggests that the colonization of the American continent was fairly simple from a emigrational point of view, but other evolutionary processes, such as genetic drift or natural selection, could have also shaped the genetic background of present day populations in the Beni region. Aim: The objective of this study is to characterize the genetic diversity of these populations by analysing the sequence variability of the HVR-I control region in the mitochondrial DNA (mtDNA). The Amerindian origin of these populations suggests that close genetic similarities should be evident between the Beni samples studied here and other Amerindian groups. However, complex processes of population interactions and/or isolation in the Beni region might result in non-expected genetic affinities. Subjects and methods: DNA was extracted from pulled-out hairs obtained in situ from non-closely related individuals living in the Beni Department in Bolivia. DNA was extracted using a standard Chelex™ 100 method and a 401 bp DNA fragment of the HVR-I region was amplified using specific primers (L-15978 and H-16412). DNA amplicons were purified by centrifugation using Microspin™ S-300 HR columns and both SNA strands were sequenced after asymmetric PCR using direct Dye-Terminator 2 sequencing kit (Perkin-Elmer). Two independent 401 and 328 bp DNA fragments were sequenced separately for each sample. The sequence analyses includes mismatch distributions and mean pairwise differences, median network analysis, and neighbour joining, maximum likelihood phylogenetic comparisons. Genetic diversity of DNA sequences was also measured in various ways for the sample studied and UPGMA trees were drawn, including a large number of South Amerindian sequences. Results: The genetic diversity of 401 nucleotide long mtDNA sequences in the hypervariable control region, from positions 16 000–16 400, was characterized in a sample of 54 Amerindians living in the Llanos de Moxos. A total of 34 distinct lineages were observed, defined by 41 variable nucleotide positions, and 70.6% of all lineages were single sequences. All four major Amerindian haplogroups were detected (A 18.5%, n=10 ; B 24.1%, n=13, C 50.0% n=27 ; and D 5.6%, n=3). The median network analysis observed suggests that processes of population expansion took place in the Beni region. However, no clear haplotype differentiation by population could be detected. High levels of molecular variability and a bimodal pair-wise mismatch distribution were seen within the sample. The analyses of molecular variance (AMOVA) showed that most of the variance observed was due to intrapopulation variability, and that the highest among-groups variance was obtained when a linguistic classification criteria was used. The phylogenetic comparison revealed unique lineages in the Beni areas, not reported for other Amerindian populations. Conclusions: The genetic diversity observed in the Beni area is higher than that observed in other American populations living in much larger areas and with a long, known evolutionary history, despite the reduced area of Moxos. This could result from processes of reproductive isolation between groups, followed by population expansions and migration, where genetic drift might have be a major evolutionary force in population differentiation.

Mitochondrial DNA diversity of the Amerindian populations living in the Andean Piedmont of Bolivia: Chimane, Moseten, Aymara and Quechua

Background: Chimane, Moseten Aymara and Quechua are Amerindian populations living in the Bolivian Piedmont, a characteristic ecoregion between the eastern slope of the Andean mountains and the Amazonian Llanos de Moxos. In both neighbouring areas, dense and complex societies have developed over the centuries. The Piedmont area is especially interesting from a human peopling perspective since there is no clear evidence regarding the genetic influence and peculiarities of these populations. This land has been used extensively as a territory of economic and cultural exchange between the Andes and Amazonia, however Chimane and Moseten populations have been sufficiently isolated from their neighbour groups to be recognized as distinct populations. Genetic information suggests that evolutionary processes, such as genetic drift, natural selection and genetic admixture have formed the history of the Piedmont populations. Aim: The objective of this study is to characterize the genetic diversity of the Piedmont populations, analysing the sequence variability of the HVR-I control region in the mitochondrial DNA (mtDNA). Haplogroup mtDNA data available from the whole of Central and South America were utilized to determine the relationship of the Piedmont populations with other Amerindian populations. Subject and methods: Hair pulls were obtained in situ, and DNA from non-related individuals was extracted using a standard Chelex™ 100 method. A 401 bp DNA fragment of HVR-I region was amplified using standard procedures. Two independent 401 and 328 bp DNA fragments were sequenced separately for each sample. The sequence analyses included mismatch distribution and mean pairwise differences, median network analyses, AMOVA and principal component analyses. The genetic diversity of DNA sequences was measured and compared with other South Amerindian populations. Results: The genetic diversity of 401 nucleotide mtDNA sequences, in the hypervariable Control Region, from positions 16 000–16 400, was characterized in a sample of 46 Amerindians living in the Piedmont area in the Beni Department of Bolivia. The results obtained indicate that the genetic diversity in the area is higher than that observed in other American groups living in much larger areas and despite the reduced size of the studied area the human groups analysed show high levels of inter-group variability. In addition, results show that Amerindian populations living in the Piedmont are genetically more related to those in the Andean than in the Amazonian populations.

Dopamine DRD2/ANKK1 Taq1A and DAT1 VNTR polymorphisms are associated with a cognitive flexibility profile in pathological gamblers

Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p < 0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p < 0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG.

Analyzing the genetic structure of the Tepehua in relation to other neighbouring Mesoamerican populations. A study based on allele frequencies of STR markers.

We report data on the genetic variation of the Tepehua population based on 15 autosomal microsatellites. The Tepehua, whose language belongs to the Totonac family, are settled throughout the Sierra Madre Oriental in Mexico and constitute a group in demographic decline. The results suggest that the Tepehua population remained isolated throughout a large part of its history. Phylogenetic analyses performed with other indigenous and admixed populations of Mesoamerica allow us to address their biological history. The results suggest a genetic affinity between the Tepehua and the Huastecos due to their previous shared history, and a certain degree of differentiation from the Otomões groups and the Choles (who are of Mayan origin). A clear genetic differentiation is also apparent between native and admixed populations within the greater region of Mesoamerica. It is currently accepted that the genetic composition of the American populations fits a trihybrid model of admixture. The genetic structure based on comparison of 34 populations throughout the continent (9 indigenous and 23 admixed) using hierarchical cluster analysis with an explained variance of 61.17% suggests the existence of four large groups distinguished according to the degree of admixture between Amerindians, Europeans, and Africans. Am. J. Hum. Biol., 2008.

Suitability of the YNZ22 (D17S5) VNTR polymorphism for legal medicine investigations in the population of Catalonia (Spain)

Allele and phenotype frequencies for the YNZ22 locus were determined in a population sample from Catalonia (Spain) using the polymerase chain reaction (PCR). In 311 unrelated individuals, 14 alleles and 56 phenotypes were observed. No deviation from Hardy-Weinberg equilibrium was found. The observed heterozygosity was 81.35%. The YNZ22 polymorphism is useful for paternity testing with a CE value of 70% and an Essen-MÖller value of 9.35 (log.)ZusammenfassungAllelfrequenzen und phänotypische Häufigkeiten des Locus YNZ22 wurden in einer katalanischen Bevölkerungsstichprobe (Spanien) mittels der Polymerase-Kettenreaktion bestimmt. 14 Allele und 56 Phänotypen wurden bei insgesamt 311 nicht verwandten Individuen beobachtet. Eine Abweichung vom Hardy-Weinberg Gleichgewicht wurde nicht festgestellt. Die Heterozygotenrate betrug 81,35%. Der Polymorphismus YNZ22 ist mit einem CE-Wert von 70% und einem EM (Essen-Möller)-Wert von 9,35 (log) zur Vaterschaftsuntersuchung geeignet.

Direct Sequencing of the Human Protamine P1 Gene and Application in Forensic Medicine

Protamines are among the most variable nuclear proteins known in eukaryotes. In order to learn more about their evolution and function in humans and to explore the possibility of potential applications in forensic medicine we have developed a rapid method to amplify and directly sequence the protamine P1 gene simultaneously in many different samples. The method takes only 3.5 h from genomic DNA to the sequencing reactions. Despite the high variability of these genes only one polymorphic site was detected at the coding region level in different individuals. This polymorphic variation does not create a change in the amino-acid sequence of the protamine. Because all the protamine genes sequenced from different species are markedly different among them as well as to the human sequence, amplification and direct sequencing of this gene can be used to unequivocally identify the human or animal origin of biological specimens. Furthermore, the single polymorphic site detected in the human P1 gene could be useful in conjunction with other markers in identification studies in humans.

HUMTH01, HUMVWA31A, HUMCSF1PO and HUMTPOX polymorphisms in Amerindian populations living in the Beni Department of Bolivia

This report presents allele frequency and absolute genotype data of the short tandem repeat (STR) loci HUMTH01, HUMVWA31A, HUMCSF1PO and HUMTPOX for three autochthonous Amerindian populations living in the Beni Department of Bolivia. These related groups are the Quechua, Aymara and Beni populations all living in specific although sometimes overlapping areas that extend from the Andean habitat to the lowland Llanos de Moxos savannah passing through the Piedmont hills. The usefulness of these loci for paternity and identification testing was also examined. The present work completes previous genetic studies performed by the authors in these populations including mtDNA haplogroups (Bert et al., Hum Biol, 73:1–16, 2001) and HVRI data (Bert et al., Ann Hum Biol 31:9–28, 2004; Corella et al., Ann Hum Biol 34:34–35, 2007).

Low apolipoprotein E ε4 allele frequency in the population of Catalonia (spain) determined by Pcr-Rflp and Laser fluorescent sequencer

Specific apolipoprotein E alleles have been associated in the last few years with several diseases using appropriate controls. However, these control groups are rarely representative of the general population since they correspond either to aged or healthy control groups (and thus depleted of pathological alleles). For this reason it is difficult at present to compare population allelic frequencies in different countries. In order to provide this essential basic data representative of the general population, in this work we have determined the distribution of apolipoprotein E alleles in 226 individuals from the population of Catalonia (Spain) sampled with the main purpose of paternity testing. The allelic frequencies are: ε2 = 0.064, ε3 = 0.810 and ε4 = 0.126, predicting a lower incidence of Alzheimer disease and possibly also of other pathologies where this allele is a risk factor.