title: Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I.
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 the SCA1 (CAG)n to expansion.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
authors.forename: M Y
authors.initials: MY
authors.lastname: Chung
authors.forename: L P
authors.initials: LP
authors.lastname: Ranum
authors.forename: L A
authors.initials: LA
authors.lastname: Duvick
authors.forename: A
authors.initials: A
authors.lastname: Servadio
authors.forename: H Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002896:Chromosomes, Human, Pair 6; D004247:DNA; D017931:DNA Primers; D005799:Genes, Dominant; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D013132:Spinocerebellar Degenerations / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004247:DNA