Background: The Austro-Asiatic linguistic family, which is considered to be the oldest of all the families in India, has a substantial presence in Southeast Asia. However, the possibility of any genetic link among the linguistic sub-families of the Indian Austro-Asiatics on the one hand and between the Indian and the Southeast Asian Austro-Asiatics on the other has not been explored till now. Therefore, to trace the origin and historic expansion of Austro-Asiatic groups of India, we analysed Y-chromosome SNP and STR data of the 1222 individuals from 25 Indian populations, covering all the three branches of Austro-Asiatic tribes, viz. Mundari, Khasi-Khmuic and Mon-Khmer, along with the previously published data on 214 relevant populations from Asia and Oceania.

Northeast India, the only region which currently forms a land bridge between the Indian subcontinent and Southeast Asia, has been proposed as an important corridor for the initial peopling of East Asia. Given that the Austro-Asiatic linguistic family is considered to be the oldest and spoken by certain tribes in India, Northeast India and entire Southeast Asia, we expect that populations of this family from Northeast India should provide the signatures of genetic link between Indian and Southeast Asian populations. In order to test this hypothesis, we analyzed mtDNA and Y-Chromosome SNP and STR data of the eight groups of the Austro-Asiatic Khasi from Northeast India and the neighboring Garo and compared with that of other relevant Asian populations. The results suggest that the Austro-Asiatic Khasi tribes of Northeast India represent a genetic continuity between the populations of South and Southeast Asia, thereby advocating that northeast India could have been a major corridor for the movement of populations from India to East/Southeast Asia.

Because of the widespread phenomenon of patrilocality, it is hypothesized that Y-chromosome variants tend to be more localized geographically than those of mitochondrial DNA (mtDNA). Empirical evidence confirmatory to this hypothesis was subsequently provided among certain patrilocal and matrilocal groups of Thailand, which conforms to the isolation by distance mode of gene diffusion. However, we expect intuitively that the patterns of genetic variability may not be consistent with the above hypothesis among populations with different social norms governing the institution of marriage, particularly among those that adhere to strict endogamy rules. We test the universality of this hypothesis by analyzing Y-chromosome and mtDNA data in three different sets of Indian populations that follow endogamy rules to varying degrees. Our analysis of the Indian patrilocal and the matrilocal groups is not confirmatory to the sex-specific variation observed among the tribes of Thailand. Our results indicate spatial instability of the impact of different cultural processes on the genetic variability, resulting in the lack of universality of the hypothesized pattern of greater Y-chromosome variation when compared to that of mtDNA among the patrilocal populations.

Fifteen SNPs from nine different genes were genotyped on 1379 individuals, 758 T2DM patients and 621 controls, from the city of Hyderabad, India, using Sequenom Massarray platform. These data were analyzed to examine the role of gene–gene and gene–environment interactions in the manifestation of T2DM. The multivariate analysis suggests that TCF7L2, CDKAL1, IGF2BP2, HHEX and PPARG genes are significantly associated with T2DM, albeit only the first two of the above 5 were associated in the univariate analysis. Significant gene–gene and gene–environment interactions were also observed with reference to TCF7L2, CAPN10 and CDKAL1 genes, highlighting their importance in the pathophysiology of T2DM. In the analysis for cumulative effect of risk alleles, SLC30A8 steps in as significant contributor to the disease by its presence in all combinations of risk alleles. A striking difference between risk allele categories, 1–4 and 5–6, was evident in showing protective and susceptible roles, respectively, while the latter was characterized by the presence of TCF7L2 and CDKAL1 variants. Overall, these two genes TCF7L2 and CDKAL1 showed strong association with T2DM, either individually or in interaction with the other genes. However, we need further studies on gene–gene and gene–environment interactions among heterogeneous Indian populations to obtain unequivocal conclusions that are applicable for the Indian population as a whole.

The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI) pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen receptor CAG repeat sizes, XCI percentages, and clinical and biochemical parameters were measured. The mean CAG repeat number is similar between the cases (18.74±0.13) and controls (18.73±0.12). The obese PCOS women were significantly more frequent in the <18 and >20 CAG repeat category than the lean PCOS women, yielding a highly significant odds (p = 0.001). Among the women with non-random X-inactivation, alleles with <19 repeats were more frequently activated among cases than controls (p = 0.33). CAG repeat polymorphism by itself cannot be considered as a useful marker for discriminating PCOS. We observed a trend of preferential activation of the shorter allele among the PCOS cases with non random XCI pattern. In the obese PCOS women, this microsatellite variation may account for the hyperandrogenicity to a larger extent than the lean PCOS women.

Background: India is a country with enormous social and cultural diversity due to its positioning on the crossroads of many historic and pre-historic human migrations. The hierarchical caste system in the Hindu society dominates the social structure of the Indian populations. The origin of the caste system in India is a matter of debate with many linguists and anthropologists suggesting that it began with the arrival of Indo-European speakers from Central Asia about 3500 years ago. Previous genetic studies based on Indian populations failed to achieve a consensus in this regard. We analysed the Y-chromosome and mitochondrial DNA of three tribal populations of southern India, compared the results with available data from the Indian subcontinent and tried to reconstruct the evolutionary history of Indian caste and tribal populations.

We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.

Among the most contentious currently debated issues is about the people who had settled first in the Indian subcontinent. It has been suggested that the communities affiliated to the Austro-Asiatic linguistic family are perhaps the first to settle in India and the palaeoanthropological evidences suggest the earliest settlement probably around 60,000 years BP. Recent speculations, based on both traditional genetic markers and DNA markers, seem to corroborate the aforesaid view. However, these studies are inadequate both in terms of the representation of the constituent groups within this broad linguistic category as well as the number of samples that represent each of them. We strongly feel that, before making any formidable conclusions on the peopling of India and/or the history of settlement, it is necessary to ascertain that the Austro-Asiatic speakers, represented by over 30 different tribal groups, either genetically constitute a homogenous single entity or are a heterogeneous conglomeration, derived from different sources. As a first step towards this we tried to collate and analyse the existing information geographic, ethno-historic, cultural and biological. The results of the analyses of anthropometric and genetic marker data indicate that the Austro-Asiatic groups, particularly the Mundari speakers, with certain exceptions, show greater homogeneity among them when compared to the other linguistic groups, although certain groups show as outliers. However, traditional genetic markers show lower within population heterozygosity compared to Dravidian and other Indian populations. This is contrary to what has been claimed in case of certain DNA markers. Given that relatively greater heterozygosity among the Austro-Asiatic populations has been taken as one of the important evidences supporting greater antiquity of these populations one should await results of detailed DNA studies being currently undertaken by us, involving a number of Austro-Asiatic and other ethnic populations of India to resolve the issue unequivocally.