Origin of the expansion mutation in myotonic dystrophy.
Myotonic dystrophy (DM) is caused by the expansion of a CTG trinucleotide repeat. The mutation is in complete linkage disequilibrium with a nearly two-allele insertion/deletion polymorphism, suggesting a single origin for the mutation or predisposing mutation. To trace this-ancestral event, we have studied the association of CTG repeat alleles in a normal population to alleles of the insertion/deletion polymorphism and of a (CA)n repeat marker 90 kilobases from the DM mutation. The results strongly suggest that the initial predisposing event(s) consisted of a transition from a (CTG)5 allele to an allele with 19 to 30 repeats. The heterogeneous class of (CTG)19-30 alleles which has an overall frequency of about 10%, may constitute a reservoir for recurrent DM mutations.
Imbert
G
G
Laboratoire de Génétique, Moléculaire des Eucaryotes, CNRS, Unité 184, INSERM, Faculté de Médecine, Strasbourg, France.
Kretz
C
C
Johnson
K
K
Mandel
J L
JL
D000483:Alleles; D001483:Base Sequence; D005075:Biological Evolution; D002888:Chromosomes, Human, Pair 19; D005600:Fragile X Syndrome / Q000235:genetics; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics; D009154:Mutation; D009223:Myotonic Dystrophy / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D044465:White People / Q000235:genetics
D005819:Genetic Markers