Deleterious mutations of the human β-globin gene are responsible for β-thalassaemia and other haemoglobinopathies, which are the most common genetic diseases in Indian populations. A highly heterogeneous distribution of those mutations is observed in India and certain mutations are restricted to some extent to particular groups only. The reasons behind the geographical clustering and origin of the mutations in India is a highly debated issue and the evidence is conflicting. Our present article aims at tracing the origin of the deleterious β-globin mutation and evaluates the role of different evolutionary forces responsible for the spread and present distribution of those mutations in Indian populations, using data from molecular biology and statistical methods. Mutations are generated essentially randomly, but «hot-spot» sites for mutation are reported for the β-globin gene cluster, indicating sequence dependency of mutation. A single origin of a deleterious β-globin mutation, followed by recombination (in a hot spot region) and/or interallelic gene conversion (within β-globin gene) through time is the most plausible hypothesis to explain the association of those mutations with multiple haplotype backgrounds and frameworks. It is suggested that India is the place of origin of HbE and HbD mutations and that they dispersed to other parts of the would by migration. HbS mutants present in Indian populations are not of Middle East origin but rather a fresh mutation is the probable explanation for the prevalence among tribal groups. β-thalassaemia represents a heterogenenous group of mutant alleles in India. Five common and twelve rare mutations have been reported in variable frequencies among different Indian populations. Gene flow of those mutant alleles from different populations of the world by political, military and commercial interactions possibly accounts for the heterogenous nature of b-thalassaemia among Indians. A multiple allelic polymorphic system of the b-globin gene exists in different populations. Dynamic interaction of the mutant alleles in the presence of different selective forces including falciparum malaria and biosocial patterns of Indian populations is discussed in order to explain the variable distribution and maintenance of those mutant alleles.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.