HAPLOTYPES IN TRIBAL INDIANS BEARING THE SICKLE GENE - EVIDENCE FOR THE UNICENTRIC ORIGIN OF THE BETA-S MUTATION AND THE UNICENTRIC ORIGIN OF THE TRIBAL POPULATIONS OF INDIA

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  • 1 August 1989
    • journal article
    • research article
    • Vol. 61  (4) , 479-491
Abstract
To determine the origin of sickle cell anemia (SS) in India, we analyzed haplotypes of the .beta. gene cluster in .beta.S-carrying individuals belonging to tribal populations living in the Nilgiris region of southern India and complemented the available data on tribes of east-central India. We found that in the Nilgiris tribes chromosomes bearing .beta.S gene are linked in 91% of the cases to the "Asian" (Arab-Indian) haplotype (although 25% of the haplotypes had the .epsilon. polymorphic site negative, making the 5'' portion of the haplotype identical with the African Senegal haplotype). These XmnI (+) chromosomes were associated with high G.gamma. expression (67.2 .+-. 5.9%) and a high percentage of Hb F (15.5 .+-. 7.9%; range, 6-25.3%). We have similar findings for tribal groups from west-central India (Gujarat). In east-central India we have confirmed the data of others, finding the same haplotype linked to .beta.S in tribes living in the east (Orissa, Andhra Pradesh). We conclude that the .beta.S gene in presently isolated and disperse tribal populations in India is associated with one predominant typical haplotype, suggesting a unicentric origin of the mutation in India. In addition, this finding implies a unicentric origin of the tribal populations themselves: The gene must have arisen and spread before tribal dispersion. Furthermore, we find extremely high frequencies of the (-.alpha.) haplotype in the Nilgiris (0.89) and in Gujarat (0.95). The .beta.S gene linkage to a high Hb F-expressing haplotype and high incidence of .alpha.-thalassemia predict a mild phenotypical of sickle cell anemia in India.