A Global Haplotype Analysis of the Myotonic Dystrophy Locus: Implications for the Evolution of Modern Humans and for the Origin of Myotonic Dystrophy Mutations

• Published in: American journal of human genetics Vol. 62; no. 6; pp. 1389 - 1402
• Main Authors: Tishkoff, S.A., Goldman, A., Calafell, F., Speed, W.C., Deinard, A.S., Bonne-Tamir, B., Kidd, J.R., Pakstis, A.J., Jenkins, T., Kidd, K.K.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.06.1998; University of Chicago Press
• Subjects: Alleles; Animals; Biological and medical sciences; Diseases of striated muscles. Neuromuscular diseases; Evolution, Molecular; Gene Frequency; Haplotype analysis; Haplotypes; Human evolution; Humans; Linkage Disequilibrium; Medical sciences; Mutation; Myotonic dystrophy; Myotonic Dystrophy - genetics; Neurology; Primates - genetics; Simple tandem-repeat polymorphism; STRP (see “Simple tandem-repeat polymorphism”); Trinucleotide Repeats; Human evolution; Myotonic dystrophy; Haplotype analysis; STRP (see “Simple tandem-repeat polymorphism”); Simple tandem-repeat polymorphism; Human; Neuromuscular diseases; Nervous system diseases; Linkage; Myotonia; Repeated sequence; Trinucleotide; Monkey; Linkage equilibrium; Genetic determinism; Population genetics; Genetic disease; Vertebrata; Allele; Mammalia; Animal; Race; Primates; Genetics; Molecular biology; Locus; Haplotype; Comparative study
• ISSN: 0002-9297; 1537-6605
• 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.