GENOMIC STRUCTURE OF THE HUMAN GENE FOR SPINOCEREBELLAR ATAXIA TYPE-2(SCA2) ON CHROMOSOME 12Q24.1

Spinocerebellar ataxia type 2 (SCA2) is a member of a group of neurode generative diseases that are caused by instability of a DNA CAG repeat , We report the genomic structure of the SCA2 gene. Its 25 exons, enco mpassing approximately 130 kb of genomic DNA, were mapped onto the phy sical map of the region, Exonic sizes varied from 37 to 890 bp, and in tronic sizes ranged from 323 bp to more than 15 kb, The CAG repeat was contained in the 5' coding region of the gene in exon 1. Determinatio n of the splice junction sequences indicated the presence of only one deviation from the GT-AG rule at the donor splice site of intron 9, wh ich contained a GC instead of a GT dinucleotide. Exon 10, immediately downstream from this rare splice donor site, was alternatively spliced , Alternative splicing does not affect the reading frame and is predic ted to encode an isoform containing 70 amino acids less. (C) 1998 Acad emic Press.