Maternal footprints of Southeast Asians in North India.

We have analyzed 7,137 samples from 125 different caste, tribal and religious groups of India and 99 samples from three populations of Nepal for the length variation in the COII/tRNA(Lys) region of mtDNA. Samples showing length variation were subjected to detailed phylogenetic analysis based on HVS-I and informative coding region sequence variation. The overall frequencies of the 9-bp deletion and insertion variants in South Asia were 1.9 and 0.6%, respectively. We have also defined a novel deep-rooting haplogroup M43 and identified the rare haplogroup H14 in Indian populations carrying the 9-bp deletion by complete mtDNA sequencing. Moreover, we redefined haplogroup M6 and dissected it into two well-defined subclades. The presence of haplogroups F1 and B5a in Uttar Pradesh suggests minor maternal contribution from Southeast Asia to Northern India. The occurrence of haplogroup F1 in the Nepalese sample implies that Nepal might have served as a bridge for the flow of eastern lineages to India. The presence of R6 in the Nepalese, on the other hand, suggests that the gene flow between India and Nepal has been reciprocal.

Allelic variation and haplotype structure of the dopamine receptor gene DRD2 in nine Indian populations.

The human dopaminergic system is a significant focal point of study in the fields of neuropsychiatry and pharmacology, plus it is also a promising nuclear DNA marker in studies of human genome diversity. In this study, we assayed six polymorphic markers in the dopamine D2 receptor gene (DRD2) in 482 unrelated individuals from nine ethnic populations of India. Our results demonstrate that the six markers are highly polymorphic in all populations and the constructed haplotypes show a high level of heterozygosity. Out of the eight possible three-site haplotypes, all populations commonly shared only three haplotypes. The haplotypes exhibited fairly high frequencies across multiple populations; Kurumba population showed all eight three-site haplotypes. The ancestral haplotype (B2-D2-Al) was observed at high frequency only in the Siddi population. Haplotypes based on all six markers revealed 16 haplotypes, out of which only 6 are most common with a frequency of greater than 5% in at least one of the nine populations. But only three haplotypes were shared by all nine populations with the cumulative frequency ranging from 80.8% (Kurumba) to 96.6% (Onge). Great variation in levels of linkage disequilibrium (LD) was detected, ranging from complete LD in the Badaga to virtually no LD in the Siddi. This range of LD likely reflects different population histories, such as African ancestry in the Siddi and recent founding events in the population isolates, Badaga and Kota.

Single nucleotide polymorphisms in alcohol dehydrogenase genes among some Indian populations.

Seven ADH genes, identified until now, located in the long arm of human chromosome 4, produce seven different isozymes involved in the metabolism of ethanol to acetaldehyde. Of the more than 500 SNPs reported in the coding and non-coding regions of these genes in the world databases, 11 are more extensively studied. Three SNPs, ADH1B Arg47His (Exon3), ADH1B Arg369Cys (Exon9) and ADH1C Val349Ile (Exon8), are functionally validated in terms of phenotype-genotype correlations and are in specific linkage disequilibrium (LD) with non-coding SNPs. However, the frequency of each SNP and configuration of LD varies among populations. The Indian populations studied were conspicuous by the complete absence of African specific allele ADH1B*369Cys, the negligible frequency of East Asian specific ADH1B*47His allele and the presence of a novel SNP ADH1B A3529G (Intron3). The ADH1C*349Ile was the only functional allele polymorphic with a strong LD block in all the populations studied and the high F(st) value observed for the non-coding ADH1B Rsa1 variant was in conformity with world populations.

Single nucleotide polymorphisms of the ALDH2 gene in six Indian populations.

BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) degrades acetaldehyde metabolized from ethanol. Its encoding gene ALDH2 has a functional polymorphism, ALDH2 Glu487Lys associated with low enzyme activity. AIM: Since Glu487Lys of this locus is fixed for the functional subunit in all non-East Asian populations, this polymorphism was examined along with G-357A promoter (SacI) and four other intronic loci to identify informative markers to study the role of this gene in Indian populations. SUBJECTS AND METHODS: A total of 397 males belonging to six ethnic populations, from four linguistic groups of India were included in the present study. No test was performed to detect the phenotype of alcoholism. Genotype of ALDH2*E487K and G-357A promoter site along with four non-coding single nucleotide polymorphisms (SNPs) in the upstream of this polymorphism were determined by PCR and sequencing. RESULTS: All of the subjects were found to have the common homozygous genotype (ALDH2*1/ALDH2*1) for the E487K site. Allele frequencies of non-coding SNPs varied among populations but genetic variance (F(st)) indicated little variation among populations. Four major SNP-defined haplotypes accounted for almost all chromosomes in all populations. The ancestral haplotype was found in high frequency in all populations and linkage disequilibrium was strong and highly significant between all sites (p < 0.05). CONCLUSION: The small number of haplotypes in this region is suggesting the strong linkage disequilibrium across the region and confirms the global long-range linkage disequilibrium around the ALDH2 locus. This study provides a baseline for future research into the role of the ALDH2 locus in alcoholism in Indian populations.