Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I

Ming Yi Chung, Laura P.W. Ranum, Lisa A. Duvick, Antonio Servadio, Huda Y. Zoghbi, Harry T. Orr

Research output: Contribution to journalArticle

410 Scopus citations

Abstract

Spinocerebellar ataxia type I (SCAI) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat on chromosome 6p. Normal alleles range from 19−36 repeats while SCA1 alleles contain 43−81 repeats. We now show that in 63% of paternal transmissions, an increase in repeat number is observed, whereas 69% of maternal transmissions showed no change or a decrease in repeat number. Sequence analysis of the repeat from 126 chromosomes reveals an interrupted repeat configuration in 98% of the unexpanded alleles but a contiguous repeat (CAG)n configuration in 30 expanded alleles from seven SCA1 families. This indicates that the repeat instability in SCA1 is more complex than a simple variation in repeat number and that the loss of an interruption predisposes theSCA1 (CAG)n to expansion.

Original languageEnglish (US)
Pages (from-to)254-258
Number of pages5
JournalNature Genetics
Volume5
Issue number3
DOIs
StatePublished - Nov 1993

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