AbstractThe present study was aimed to study HLA-DRB1, -DQB1 alleles and haplotypes of two endogamous groups of South India. PCR-SSP typing of HLA-DRB1, -DQB1 alleles were performed on 63 Mukkuvar, primarily a coastal population and 101 Valayar, a population primarily living on the fringes of forest areas. Genetic distances, neighbor-joining dendrograms and correspondence analysis have been performed. The HLA class II alleles, DRB1*07 (32.5%), DRB1*15 (23.0%), DRB1*13 (11.1%) and DRB1*12 (10.3%) were more frequent among Mukkuvar. Among Valayar, DRB1*12 (18.8%), DRB1*15 (17.3%), DRB1*04 (15.4%), DRB1*07 (13.4%) and DRB1*10 (10.9%) were more frequent. Similarly, DQB1*06 (38.1%), DQB1*02 (26.2%) and DQB1*05 (20.5%) alleles among Mukkuvar and DQB1*06 (40.2%) and DQB1*05 (28.9%) among Valayar were more frequent. We genotyped the two most common South Indian two-locus haplotypes, such as DRB1*15-DQB1*06 and DRB1*07-DQB1*02 for HLA-A, -B and -C alleles to identify the 5-locus extended haplotypes. We identified the presence of a highly unique extended haplotype A*03-B*35-C*12-DRB1*07-DQB1*02 in Valayar (HF: 0.2777) and Mukkuvar (HF: 0.1666) hitherto not reported in any of the world populations. The HLA-DRB1 allele based phylogenetic analysis have demonstrated the unique and distinct phylogenetic relatedness of Mukkuvar and Valayar with other ethnic populations. The coastal population Mukkuvar is more closely related to Hispanic and Guanche populations. However, the Valayar revealed phylogenetic relatedness with Austronesian and Micronesian populations supporting the theory of coastal migrations of Out-of-Africa ancestral founding populations.