Founder effect in spinal and bulbar muscular atrophy (SBMA).
We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X chromosomes and 173 control X chromosomes in Japanese males. The control chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32 repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/- 3 copies. The control chromosomes had seven different alleles of the (GGC)n repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%), while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distribution was significantly different between SBMA and control chromosomes (P < 0.0001), indicating the presence of linkage disequilibrium. There was no allelic association between the (CAG)n and (GGC)n microsatellites among control subjects as well as SBMA patients, which suggests that a founder effect makes a more significant contribution to generation of Japanese SBMA chromosomes than new mutations.
Tanaka
F
F
Department of Neurology, Nagoya University School of Medicine, Japan.
Doyu
M
M
Ito
Y
Y
Matsumoto
M
M
Mitsuma
T
T
Abe
K
K
Aoki
M
M
Itoyama
Y
Y
Fischbeck
K H
KH
Sobue
G
G
D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D016472:Motor Neuron Disease / Q000235:genetics*; D009133:Muscular Atrophy / Q000235:genetics*; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
D011944:Receptors, Androgen