DNA sequence variation and haplotype structure of the ICAM1 and TNF genes in 12 ethnic groups of India reveal patterns of importance in designing association studies

We have examined the patterns of DNA sequence variation in and around the genes coding for ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India. We aimed to (a) quantify the nature and extent of the variation, and (b) analyse the observed patterns of variation in relation to population history and ethnic background. At the ICAM1 and TNF loci, respectively, the total numbers of SNPs that were detected were 28 and 12. Many of these SNPs are not shared across ethnic groups and are unreported in the dbSNP or TSC databases, including two fairly common non-synonymous SNPs at positions 13487 and 13542 in the ICAM1 gene. Conversely, the TNF-376A SNP that is reported to be associated with susceptibility to malaria was not found in our study populations, even though some of the populations inhabit malaria endemic areas. Wide between-population variation in the frequencies of shared SNPs and coefficients of linkage disequilibrium have been observed. These findings have profound implications in case-control association studies

Mitochondrial DNA variation in ranked caste groups of Maharashtra (India) and its implication on genetic relationships and origins

Backgroud: Polymorphism in mitochondrial DNA have been proven to be useful in studying genetic relationships and origins. The origins of caste populations have remained an enigma and genetic relationships among ranked caste groups are not uniform across geographical regions in India. Aim: This study was undertaken to investigate the nature and extent of mtDNA variation and relationships among caste groups of the western Indian State of Maharashtra and examine the implication of the results on their origins. Subjects And Methods: One population was selected from each of the three caste ranks and blood samples were obtained with informed consent from unrelated individuals. The ranked caste populations were: upper (Brahmin; n=31), middle (Maratha; n=41), and lower (Nava Baudh; n=40). Ten relevant restriction site polymorphisms (RSPs) and one Insertion/Deletion (InDel) polymorphism were studied. The Hypervariable Segment 1 (HVS1) was sequenced in a subset of sampled individuals. Results: Four RSP loci were found to be monomorphic in all populations. The InDel locus was monomorphic in two (Brahmin and Maratha) populations. One haplotype, constructed on the basis of the RSPs, was found to be predominant in all populations. Haplotype diversity was of similar magnitudes among Maratha and Nava Baudh (68% and 64%, respectively), and was much higher than among the Brahmin (49%). The frequency of haplogroup M was found to be high in all three groups, but, contrary to expectations, was highest in the upper caste Brahmin. About 10% of Brahmins, however, possessed the haplogroup C. Extensive variation was found in the HVS1 region. The nucleotide diversities and mean number of mismatches were found to be of similar magnitudes in all three groups. Conclusions: The upper caste group, Brahmin, is genetically distinct from the middle and lower caste groups. However, in view of the highest frequency of haplogroup M among the Brahmin, it appears that there may have been recruitment from other populations into this group