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.
Highlights
Spinocerebellar ataxia type 1 (SCA1) and MachadoJoseph disease (MJD/SCA3) are autosomal dominant neurodegenerative diseases caused by expansions of a CAG repeat in the SCA1 and MJD genes, respectively
In the segregation distortion analysis, 367 trios were analyzed for the SCA1 locus, including 734 meioses (Table 1), and 879 trios for the MJD locus, totaling 1758 meioses (Table 2)
No segregation distortion for the SCA1 alleles was revealed by the analysis of informative meioses (p = 0.8516 and p = 0.3604, for 257 maternal and 269 paternal meioses, respectively; Table 1) no distortion was observed for the MJD locus either (Table 2), analyzed in 745 maternal and 695 paternal informative meioses (p = 0.6339 and p = 0.2713, respectively)
Summary
Spinocerebellar ataxia type 1 (SCA1) and MachadoJoseph disease (MJD/SCA3) are autosomal dominant neurodegenerative diseases caused by expansions of a CAG repeat in the SCA1 and MJD genes, respectively. Segregation distortion favoring the transmission of mutated or normal alleles during meiosis has been reported for both genes. Rubinsztein and Leggo (1997) added to these observations, reporting the preferential transmission of alleles with smaller CAG repeats by normal females. Mac Millan et al (1999) did not find any evidence of segregation distortion upon transmission of CAG repeat alleles by normal individuals. Normal variation in size of the CAG repeats of SCA1 and MJD genes has been reported in a few surveys Departamento de Genética, Faculdade de Medicina, USP, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
