TY - JOUR
T1 - Founder effect in spinal and bulbar muscular atrophy (SBMA)
AU - Tanaka, Fumiaki
AU - Doyu, Manabu
AU - Ito, Yasuhiro
AU - Matsumoto, Michiyo
AU - Mitsuma, Terunori
AU - Abe, Koji
AU - Aoki, Masashi
AU - Itoyama, Yasuto
AU - Fischbeck, Kenneth H.
AU - Sobue, Gen
N1 - Funding Information:
Part of this work was supported by grants from the Ministry of Welfare and Health of Japan, the Uehara Memorial Research Foundation, the Muscular Dystrophy Association and the National Institutes of Health.
PY - 1996/9
Y1 - 1996/9
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/5.9.1253
DO - 10.1093/hmg/5.9.1253
M3 - Article
C2 - 8872464
AN - SCOPUS:10144259358
SN - 0964-6906
VL - 5
SP - 1253
EP - 1257
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 9
ER -