A global haplotype analysis of the myotonic dystrophy locus: Implications for the evolution of modern humans and for the origin of myotonic dystrophy mutations

Haplotypes consisting of the (CTG)(n) repeat, as well as several flanking markers at the myotonic dystrophy (DM) locus, were analyzed in normal individuals from 25 human populations (5 African, 2 Middle Eastern, 3 European, 6 East Asian, 3 Pacific/Australo-Melanesian, sind 6 Amerindian) and in five nonhuman primate species. Non-African populations have a subset of the haplotype diversity present in Africa, as well as a shared pattern of allelic association. (CTG)(18-35) alleles (large normal) were observed only in northeastern African and non-African populations and exhibit strong linkage disequilibrium with three markers flanking the (CTG)(n) repeat. The pattern of haplotype diversity and linkage disequilibrium observed supports a recent African-origin model of modern human evolution and suggests that the original mutation event that gave rise to DM-causing alleles arose in a population ancestral to non-Africans prior to migration of modern humans out of Africa.