Founder effect in spinal and bulbar muscular atrophy (SBMA)

We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgenreceptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy(SBMA) X chromosomes and 173 control X chromosomes in Japanese males. Thecontrol chromosomes had an average CAG repeat number of 21 +/- 3 with arange from 14-32 repeat units, and SBMA chromosomes had a range from 40-55with a median of 47 +/- 3 copies. The control chromosomes had sevendifferent alleles of the (GGC)n repeat with the range of 11 to 17; the mostfrequent 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 frequentsize of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distributionwas significantly different between SBMA and control chromosomes (P <0.0001), indicating the presence of linkage disequilibrium. There was noallelic association between the (CAG)n and (GGC)n microsatellites amongcontrol subjects as well as SBMA patients, which suggests that a foundereffect makes a more significant contribution to generation of Japanese SBMAchromosomes than new mutations.