title: A global haplotype analysis of the myotonic dystrophy locus: implications for the evolution of modern humans and for the origin of myotonic dystrophy mutations.
abstract: 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.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Tishkoff
authors.forename: A
authors.initials: A
authors.lastname: Goldman
authors.forename: F
authors.initials: F
authors.lastname: Calafell
authors.forename: W C
authors.initials: WC
authors.lastname: Speed
authors.forename: A S
authors.initials: AS
authors.lastname: Deinard
authors.forename: B
authors.initials: B
authors.lastname: Bonne-Tamir
authors.forename: J R
authors.initials: JR
authors.lastname: Kidd
authors.forename: A J
authors.initials: AJ
authors.lastname: Pakstis
authors.forename: T
authors.initials: T
authors.lastname: Jenkins
authors.forename: K K
authors.initials: KK
authors.lastname: Kidd
mesh_terms: D000483:Alleles; D000818:Animals; D019143:Evolution, Molecular; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics*; D011323:Primates / Q000235:genetics; D018911:Trinucleotide Repeats