title: 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.
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 the 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 the high incidence of alpha-thalassemia predict a mild phenotypical expression of sickle cell anemia in India.
authors: D
authors: D
authors: Labie
authors: R
authors: R
authors: Srinivas
authors: O
authors: O
authors: Dunda
authors: C
authors: C
authors: Dode
authors: C
authors: C
authors: Lapoumeroulie
authors: V
authors: V
authors: Devi
authors: S
authors: S
authors: Devi
authors: K
authors: K
authors: Ramasami
authors: J
authors: J
authors: Elion
authors: R
authors: R
authors: Ducrocq
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D000883:Anthropology; D005319:Fetal Hemoglobin / Q000235:genetics; D008040:Genetic Linkage; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000235:genetics; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D007194:India; D009154:Mutation; D012424:Rural Population; D013789:Thalassemia / Q000150:complications / Q000235:genetics
chemical_list: D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D005319:Fetal Hemoglobin