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

Am J Hum Genet. 1998 Jun;62(6):1389-402. doi: 10.1086/301861.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Evolution, Molecular*
  • Gene Frequency
  • Haplotypes*
  • Humans
  • Linkage Disequilibrium
  • Mutation*
  • Myotonic Dystrophy / genetics*
  • Primates / genetics
  • Trinucleotide Repeats