Meiotic stability and polymorphism of CAG repeat in normal chromosome at SCA1 locus
- Louisiana State Univ., New Orleans, LA (United States)
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder associated with an unstable and expanded CAG repeat. We analyzed the CAG repeat in normal chromosomes from various sources including SCA1 and nonSCA1 families, and Caucasian, African American, Eskimo, South American Indian and Acadian populations. The range of CAG repeats is 10-37 in normal alleles while the disease allele contains 45-65 repeats in our studies. To determine unbiased normal allelic frequencies, we analyzed data from unrelated individuals in each group. The significance of differences in allelic frequencies among the groups was determined by a chi-square test. Caucasian and Acadian frequencies were similar (p = 0.23), but highly significant differences were found among the Caucasians, African Americans, Eskimos, and South American Indians (p < 0.0005), and the range of allele sizes was much narrower in Eskimos and South American Indians. To determine if the normal chromosome is susceptible to meiotic instability, we examined members of 19 Caucasian and 24 Acadian families. Normal sized CAG repeats were faithfully transmitted from parents to offspring without any alteration in CAG number in 236 meioses. Transmission of CAG repeats in normal alleles were also stable in our SCA1 family. However, the disease allele was associated with a significant degree of instability. Some patients showed 2 expanded bands in DNA prepared from untransformed blood cells. This finding suggest mitotic instability of the disease allele.
- OSTI ID:
- 134062
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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