The SCA1 (Spinocerebellar ataxia type 1) and MJD (Machado-Joseph disease) CAG repeats in normal individuals: segregation analysis and allele frequencies

ABSTRACT

Spinocerebellar ataxia type 1 (SCA1) and Machado-Joseph disease (MJD/SCA3) are autosomal dominant neurodegenerative diseases caused by expansions of a CAG trinucleotide repeat in the SCA1 and MJD genes. These expanded sequences are unstable upon transmission, leading to an intergeneration increase in the number of repeats (dynamic mutation). The transmission of the CAG repeat was studied in normal mother-father-child trios, referred for paternity testing (SCA1, n = 367; MJD, n = 879). No segregation distortion was detected. The CAG allele frequencies were determined in 330 unrelated individuals (fathers from couples tested for paternity). The allele frequency distributions did not differ from those previously reported for European populations. The estimated values for the statistic parameters indicating diversity at the SCA1 locus did not differ much from those reported previously for other STRs in the Brazilian population, while those for the MJD locus were close to or higher than the maximum values of previous reports. This shows that SCA1 and MJD are highly informative loci for applications in genetic and population studies and for forensic analysis: