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, and 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.
Bibliographical noteFunding Information:
This work was supported in part by U.S. Public Health Service grants MH39239, and MH50390 (to K.K.K.), by National Science Foundation grant SBR9632509 (to J.R.K.), by a South Africa Medical Research Council grant (to T.J.), by a CIRIT (Catalonia, Spain) postdoctoral fellowship (awarded to F.C.), and by a Sloan postdoctoral fellowship in molecular evolution (awarded to S.A.T.). Collection of human population samples used for these studies was supported in part by U.S. Public Health Service grant AA09379 and by an Alfred P. Sloan foundation grant (both to K.K.K. and J.R.K.). We want to thank the individuals who donated the samples that made this study possible, and we also want to thank the numerous colleagues who assisted us in assembling the collection of samples.