Variation in the number of CAG repeats in the Machado-Joseph disease gene (MJD1) in the Japanese population

Variation in the number of CAG repeats in the Machado-Joseph disease gene ( MJD1) was examined by polymerase chain reaction and denaturing polyacrylami de gel electrophoresis analysis of 2134 normal and 135 affected chromosomes of Japanese individuals. The number of repeats ranged from 14 to 47 in nor mal alleles and from 61 to 84 in disease-associated alleles. The most frequ ent and lowest number of repeats was 14. The size distribution of normal MJ D1 alleles did not fit a normal distribution curve, but was tetramodal. Rep eats from 14 to 17, 18 to 23, 24 to 25, and 26 to 47 units were designated groups A through D, respectively. When examined Hardy-Weinberg equilibrium by chi-square analysis of goodness of fit, no evidence of significant devia tion from the Hardy-Weinberg equilibrium was observed [x(2)=4.248<16.919 (P =0.05), df=9]. The observed distribution peak of normal MJD1 alleles corres ponding to peptides containing 10, 15, 20, and 24 glutamine suggests that s tretches of 5 and 10 glutamine might constitute a functional domain of huma n MJD1, (C) 1999 Elsevier Science B.V. All rights reserved.