Analysis of beta-globin gene haplotypes in Asian Indians: origin and spread of beta-thalassaemia on the Indian subcontinent.
beta-globin gene haplotypes were determined for 196 normal (beta-A) and 419 thalassaemia (beta-Th) chromosomes of individuals from four different regions of the Indian subcontinent; North-west Pakistan, Gujarat, Punjab and Sindh. Analysis of beta-A and beta-Th haplotypes and haplotype-mutation associations in each regional group along with a consideration of Indian history provided information about the origin and spread of beta-thalassaemia mutations on the Indian subcontinent. The data are consistent with relatively recent and local origins for most beta-thalassaemia mutations. The frequencies of particular alleles differ markedly in various regions and these may be useful population markers. Of the high frequency alleles, intervening sequence 1 (IVS-1) nucleotide 5 (G-C) and codons 41/42 (-CTTT) appear to be older as suggested by multiple haplotype associations and a widespread geographical distribution. The microepidemiology of beta-thalassaemia in this region reflects considerable ethnic diversity, gene flow from population migration and natural selection by malaria infection.
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
N Y
NY
Varawalla
A C
AC
Fitches
J M
JM
Old
D001483:Base Sequence; D015139:Blotting, Southern; D004277:DNA, Single-Stranded; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
D004277:DNA, Single-Stranded; D005914:Globins