Did human DRD2 haplotypes originate in India? A survey of haplotype frequencies and linkage disequilibrium in the tribes of Eastern Ghats, South India

In recent years, a possible role of the dopamine D2 receptor (DRD2) locus has been reported in various fields like the etiology of alcoholism, neuropsychiatric disorders, etc. Therefore, it has been the focus of considerable attention. DNA analysis has made it easier to study haplotypes, arrays of alleles at closely linked loci along the chromosome. These regions are short enough to show little or no recombination, and behave as blocks that might have ancient origins. Scoring these markers as haplotypes, allows analysis both in terms of haplotype frequencies and identity in terms of linkage disequilibrium. The human dopaminergic system is an important focus of study in the fields of neuropsychiatry and pharmacology; it is also a promising nuclear DNA marker in studies of human genome diversity. Haplotype frequencies and linkage disequilibrium for the dopamine D2 receptor gene (DRD2) were determined in 197 unrelated individuals from four tribal populations of the Eastern Ghats, an important region of India. The three marker systems in this study are highly polymorphic in all the four tribal populations and the haplotype system showed high levels of heterozygosity than the Nilgiri Hill tribes and those in other parts of the world, except Africa. Out of the possible eight haplotypes, seven are commonly shared by all the populations. The ancestral allele B2D2Al accounts for 0.028 to 0.166, which was present in all the groups consistently. The linkage disequilibrium was statistically significant in all the populations. The results show a chance of Indian origin or back migration of human DRD2 haplotypes. Data obtained in this study on DRD2 represent one of the small, but growing number of datasets examining disequilibrium and haplotype frequencies in human populations and also indicate that the gene flows from the Eastern Ghats to the Western Ghats. These populations might be one of the oldest among other Indian populations.