HLA-DRB1* and DQB1* allele and haplotype diversity in eight tribal populations: Global affinities and genetic basis of diseases in South India.

The distribution of HLA class-II DRB1* and DQB1* alleles/ haplotypes were studied in 438 individuals of 8 Dravidian tribal groups inhabiting the Western Ghats, south India. The HLA typing was performed by PCR-SSP method. In order to identify the 5-locus Ancestral Extended Haplotypes (AEH), the alleles of HLA-A, -B and -C loci were typed for DNAs with predominant 2-locus haplotypes. The analyses have revealed allele HLA-DRB115 as the most predominant allele (Lowest / Highest range: Urali, 14.81 / Malasar, 48.94), followed by the alleles DRB110 (Katunayakan, 1.85 / Paliyan, 48.21), DRB114 (Paliyan 4.46 / Katunayakan, 40.74), DRB112 (Mannan, 1.64 / Katunayakan, 20.37) and DRB103 (Mannan, 1.64 / Urali, 29.63). The most frequent DQB1 alleles were DQB102 (Paliyan 3.57 / Urali, 23.15), DQB105 (Katunayakan, 27.77 / Paliyan 84.82) and DQB106 (Malasar, 8.51 / Kuruman, 33.51). The most predominant two-locus haplotypes observed were DRB115-DQB105, DRB110-DQB105, DRB115-DQB106 and DRB104-DQB105. The present study of HLA immunogenetics of south Indian tribes have revealed the presence of globally shared two and 5-locus haplotypes. Many of these haplotypes were implicated in a number of diseases in south India. We observed the presence of ancestral extended haplotypes (AEHs), hitherto not reported in Indian populations such as, A68-B35-C02-DRB115:01-DQB105:01, A24-B57-C06-DRB104:01-DQB105:01 and A24-B35-C02-DRB115:01-DQB105:02. The dendrogram based phylogenetic analyses have revealed the Caucasian affinity of Urali, palaeo-Mediterranean and Indo-European affinity of Malasar tribes. The presence of globally shared susceptible and protective haplotypes reiterated the mosaic immunogenetic fabric of south Indian tribes.