NAT2 gene diversity and its evolutionary trajectory in the Americas.

N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.

Allele and genotype frequencies of metabolic genes in Native Americans from Argentina and Paraguay.

Interethnic differences in the allele frequencies of CYP2D6, NAT2, GSTM1 and GSTT1 deletions have been documented for Caucasians, Asians, and Africans population. On the other hand, data on Amerindians are scanty and limited to a few populations from southern areas of South America. In this report we analyze the frequencies of 11 allele variants of CYP2D6 and 4 allele variants of NAT2 genes, and the frequency of GSTM1 and GSTT1 homozygous deleted genotypes in a sample of 90 donors representing 8 Native American populations from Argentina and Paraguay, identified as Amerindians on the basis of their geographic location, genealogical data, mitochondrial- and Y-chromosome DNA markers. For CYP2D6, 88.6% of the total allele frequency corresponded to *1, *2, *4 and *10 variants. Average frequencies for NAT2 *4, *5, *6 and *7 alleles were 51.2%, 25%, 6.1%, and 20.1%, respectively. GSTM1 deletion ranged from 20% to 66%, while GSTT1 deletion was present in four populations in less than 50%. We assume that CYP2D6 *2, *4, *10, *14; NAT2 *5, *7 alleles and GSTM1 and GSTT1 *0/*0 genotypes are founder variants brought to America by the first Asian settlers.

Patterns of variation in a caste-cluster of Dhangars of Maharashtra, India.

We study patterns of variation among the 20 endogamous groups of Dhangars, a caste-cluster from Maharashtra State of India, who are semi-nomadic shepherds and cattle herders. To understand patterns of variation, we subjected the data on fourteen anthropometric measurements of about 2,500 adult males and data on 6 genetic markers, published among 13 of the 20 Dhangar castes, to R-matrix analysis, Harpending and Ward model of regression of heterozygosity on the distance from centroid of the populations, spatial autocorrelation analysis and Mantel statistics of matrix correspondence of the distances--geographic, anthropometric and genetic. Results of multiple regression analysis suggest a high degree of association between allele frequencies and the geographic longitude and latitude; R2 value suggests that about 70% of the variance in RH7 and ACP can be assigned to geographic distribution of groups. In case of anthropometry, this association with body size is found to be even stronger. Results of spatial autocorrelation analysis, as suggested by Moran's (I), are somewhat complementary to those based on multiple regression analysis. Mantel test indicates significant association between anthropometric distances and the geographic distances, not between geographic and genetic distances. The extent of differentiation of Dhangar sub-castes is much higher in anthropometric traits (F(ST) = 0.068) when compared to the genetic markers (F(ST) = 0.023). Yet, the F(ST) value obtained forgenetic markers is larger than the average for the Indian populations, based on similar class of markers. The positioning of the groups in the multivariate space reflects primarily geographic proximity of the groups with reference to anthropometric dimensions while no tangible pattern is evident forgenetic markers. The plot of average heterozygosity of the groups versus their distance from the gene frequency centroid seems to reflect population size variation, rather than group variation in external gene flow.

Spatial patterns of anthropometric variation in India with reference to geographic, climatic, ethnic and linguistic backgrounds.

BACKGROUND: Anthropometric variation can be fruitfully utilized to investigate microevolutionary processes. Anthropometric variations in the Indian subcontinent based on stature and three indices (Cephalic Index, Nasal Index, and Total Facial Index) are highly variable and discriminative among populations across geographical regions. AIMS: Anthropometric variation in stature, Cephalic Index (CI), Nasal Index (NI) and Total Facial Index (TFI) were investigated with respect to ethnic, linguistic, geographical and climatic affiliation, across the Indian subcontinent. SUBJECTS AND METHODS: Published data on anthropometric variations of 531 populations from the Indian subcontinent were analysed using discriminant analysis and spatial autocorrelation analysis. RESULTS: Discriminant analysis of the four anthropometric variables shows that stature and NI are good discriminators for populations of different languages. Stature, NI and CI discriminate well among populations of diverse ethnic origin and climatic conditions in different regions. TFI is not a good discriminator for populations of diverse ethnic, linguistic and climatic attributes. Spatial autocorrelation analysis showed significant departure from randomness, suggesting geographic structuring. The Moran's I estimate is positive and statistically significant for the four variables at low distances but exhibits significant negative association at higher values. CONCLUSION: The results suggest geographical clines for the four anthropometric variables and indicate the influence of population structure on the studied variables.

Applications of pooled DNA samples to the assessment of population affinities: short tandem repeats.

Pooled DNA samples have been used in association studies of Mendelian disease genes. This method involves combining equal quantities of DNA from patients and control subjects into separate pools and comparing the pools for distributions of genetic markers. In this study identical quantities of DNA from 300 individuals representing 6 populations were pooled and amplified for 296 loci using the touchdown polymerase chain reaction (PCR) method. The purpose of this study is to test the efficacy of pooled DNA markers in the reconstruction of the genetic structure of human populations. The populations sampled included Chuvash, Buryats, Kizhi, Native Americans, South Africans, and New York City whites. To test the accuracy of the allele-frequency distributions, we genotyped the Buryats and New York samples individually for six microsatellite markers and compared their frequencies to the allele frequencies derived from the electropherogram peak heights for the pooled DNA, producing a correlation of 0.9811 with a variance of less than 0.04. Two-dimensional scaling of genetic distances among the six populations produced clusters that reflected known historical relationships. A distance matrix was created using all 296 loci, and matrices based on individual chromosomes were correlated against the total matrix. As expected, the largest chromosomes had the highest correlations with the total matrix, whereas one of the smallest chromosomes, chromosome 22, had the lowest correlation and differed most from the combined STR distance matrix.

Dermatoglyphics of the Chorote indians and their relationships with other inhabitants of the Gran Chaco.

The present report deals with digital and palmar dermatoglyphics of a sample of 98 Chorote indians, collected in the north of Argentina, in the Gran Chaco region. Bimanual dimorphism was observed in males and females, both in finger and in palmar variables. Significant differences between sexes appear only in digital ridge counts and in the combined incidence of the four pattern types the Chorote, in general, show low sexual dimorphism. Univariate comparisons carried out with other tribes of the Gran Chaco (Chiriguano, Pilagá, Mataco, and Toba) indicate statistically significant differences between these and the Chorote, both in males and females. The greatest differences were found in relation to the Mataco, who belong to the same linguistic family as the Chorote. Probable explanations for these differences are proposed.

Dermatoglyphic relationships among South Amerindian populations.

The biological affinities among 17 South American aboriginal populations are examined by means of a multivariate analysis of their dermatoglyphic finger patterns. Different analytical methods [cluster analysis, nonmetric multidimensional scaling, and multiresponse permutation procedure (based on distances derived from principal components analysis)] reveal interpopulation relationships consistent with Loukotka's language classification. The paleo-American tribes from the Gran Chaco and Brazil share a high incidence of whorls as a distinctive feature. The Andean and tropical forest groups, which present a greater prevalence of arches and ulnar loops, appear to be closely related to each other, suggesting a more recent common origin and/or substantial gene flow between them.

Dermatoglyphics in Araucanian Indians from Patagonia and multivariate comparisons with other Argentinian aboriginal populations.

Digital and palmar dermatoglyphics are reported for 94 Araucanian Indians from the Argentinian Patagonia. All the traits analyzed present values within the range of variation found in South Amerindians. The principal finding is the different behavior observed for the digital and palmar traits of the individuals of the tribe. Although finger variables show high sexual and bimanual variation (especially in males), palmar traits exhibit extreme homogeneity. Multiple discriminant analyses from palmar data and finger ridge counts separately were carried out with three other Argentinian Indian populations from the Gran Chaco. The results indicate high discrimination between the populations in both palmar variables and finger ridge counts. However, although the nature of interpopulation relationships obtained from palmar data conforms to the ethnohistorical and geographic patterns, no clear picture emerges when the finger ridge counts are used.

Absence of the 9-bp deletion of mitochondrial DNA in pre-Hispanic inhabitants of Argentina.

We investigated the incidence of the Region V mitochondrial DNA 9-base-pair (bp) deletion from human remains recovered from several archaeological sites and contexts throughout Argentina. Of the 34 samples analyzed, 24 yielded DNA extractions that gave clear amplification results. All of the individuals carried two repeats of the 9 bp, one of which has been shown to be deleted in some individuals of Asian origin and defines mitochondrial lineage B. Although most of the modern Amerindian groups in the region exhibit the deletion in high frequencies, the absence of the 9-bp deletion among ancient populations of South America seems to be the rule rather than the exception, as was reported by several studies involving extinct populations. The evidence gathered until now suggests that the earliest settlers of this region of South America did not carry mitochondrial lineage B.

Population structure and genetic differentiation among the substructured Vysya caste population in comparison to the other populations of Andhra Pradesh, India.

OBJECTIVES: The present paper focuses on the study of the patterns of genetic microdifferentiation among one of the substructured caste populations of Andhra Pradesh, namely Vysya, with reference to 17 other Telugu speaking populations from the same region of India. SUBJECTS AND METHODS: A total of 302 individuals from the three Vysya subgroups (101 of Arya Vysya, 100 from Kalinga Vysya and 101 from Thrivarnika) were typed in 17 blood groups and protein polymorphisms. Nei's gene diversity analysis, as well as neighbour-joining tree and UPGMA cluster diagrams, derived from standard genetic distances, R-matrix analysis and a regression model for investigating the patterns of external gene flow and genetic drift due to isolation under the island model, were done at two levels: (1) considering only the three Vysya populations and (2) considering common loci among 20 populations of Andhra Pradesh. RESULTS: Seven of the 17 systems investigated were found to be monomorphic among all the three Vysya groups. The UPGMA tree and bidimensional scaling of the D(2) distances derived from R-matrix analysis show a very distinct cluster of Vysya populations. Application of the model of regression of average heterozygosity versus the distance of populations from the centroid shows the three Vysya populations placed as clear outliers above the theoretical regression line. CONCLUSIONS: Different approaches employed in this study give support to the hypothesis of different origin and/or demographic story for the three Vysya groups compared with other populations of Andhra Pradesh.

Genetic structure of Native Andean populations from Argentina inhabiting different altitudes.

On the basis of erythrocyte and serum protein polymorphisms, we investigated the level of genetic differentiation among 3 Argentinian native populations sharing ethnic and morphological characteristics but inhabiting different altitudes in the Andes. Of the 15 loci studied, 8 are monomorphic. Phenotype distribution of the polymorphic systems are in agreement with Hardy-Weinberg equilibrium, except for malic enzyme (MOD), where a silent allele was found. The 2 highland populations exhibit a close genetic similarity, probably as a result of intense gene flow. The lowland population shows reduced genetic diversity, which suggests the influence of stochastic phenomena such as the founder effect.

Protein polymorphism in three South Amerindian populations.

Electrophoretic polymorphism at loci coding for blood red cells and plasma proteins was analysed in three native populations of South America: Mataco and Macá (from the Gran Chaco), and Guayaki (from the Paraguayan forest). Mean heterozygosity per locus varied from 0.024 and 0.073, the Macá being the most polymorphic population, probably reflecting admixture with the caucasoid population of Asuncion city. Although the external phenotype, blood group frequencies and ethno-linguistic affiliation of the Guayaki clearly differ from those of the Chaco tribes, Nei's genetic distances were very low and almost equidistant among the three populations. Heterogeneity of F(ST) values among polymorphic loci would suggest the action of natural selection.

Mitochondrial DNA haplogroups in Amerindian populations from the Gran Chaco.

Mitochondrial DNA from 141 individuals was typed for diagnostic restriction sites and the 9-bp region V deletion to examine the distribution of the founding mtDNA lineage haplotypes in three Amerindian populations (Mataco, Toba, and Pilagá) who currently inhabit the Argentinian part of the Gran Chaco. All four lineages were identified in the three tribes and four population samples studied. Disregarding ethnic or geographic origin, haplogroups B and D exhibit high incidence among the Gran Chaco inhabitants, whereas haplogroups A and C are present in a lower frequency. Three individuals possess none of the characteristic markers and, therefore, could not be assigned to one of those lineages. A neighbor-joining representation of F(ST) distances reflects the current geographic location of the populations, and this also corresponds to their historic distribution. After separating South America into four major regions (Tropical Forest, Andes, Gran Chaco, and Patagonia-Tierra del Fuego), the Gran Chaco populations present the highest average intragroup variability (Hs = 0.64) as well as the lowest intergroup diversity (G(')(ST) = 0.06). These findings suggest high levels of gene flow among the Chaco tribes, as well as with neighbor populations from outside the region.

Apolipoprotein B signal peptide polymorphism distribution among south Amerindian populations.

We report the distribution of the APOB signal peptide polymorphism in 5 native populations of South America: 2 samples of Mataco and 1 sample each of Pilagá and Toba from the Argentinian Chaco and 1 sample of Ache from the Paraguay forest. A randomly selected subsample of a previously studied sample from the Cayapa of Ecuador (Scacchi et al. 1997) was reanalyzed to investigate probable differences attributable to sampling, laboratory techniques, or interobserver error. The polymorphism observed in the signal peptide region of the APOB gene among native populations of South America exhibits the same range of variation found among geographic continental populations, confirming the high genetic heterogeneity of South Amerindians. Extremes in the allele prevalences were found among the Mataco and Ache, populations not far apart geographically. The small differences in genotype and allele frequencies between the subsample of the Cayapa analyzed here and the original Cayapa sample and between the 2 Mataco samples were not statistically significant and most likely were due to sampling error.