Genomic organisation of the spinocerebellar ataxia type 7 (SCA7) gene responsible for autosomal dominant cerebellar ataxia with retinal degeneration

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA type I I) is a progressive neurodegenerative disorder caused by a CAG expansion in the spinocerebellar ataxia 7 (SCA7) gene. Here, we describe the genomic or ganisation of the human SCA7 gene. The exon-intron boundaries were identifi ed by sequencing plasmid subclones of a P1 artificial chromosome (PAC) clon e containing the entire SCA7 gene. We found 13 exons, ranging in size from 69 to 979 bp, with all exon-intron boundaries following the GT-AG rule. The ATG initiation codon at position 554 of the cDNA occurs in exon 3 at posit ion 12 and the coding region extends to the first five codons of exon 13, w ith the CAG repeat being located in exon 3 starting at codon 30. The intron sizes wee determined by long-distance polymerase chain reaction with prime rs from neighbouring exons and by restriction mapping of the SCA7 PAC clone . The introns varied in size from 233 bp to about 40 kb, resulting in an ov erall size estimate for the SCA7 gene of 140 kb. Sequence analysis of intro n 7 (491 bp) revealed a polymorphic GT/AC repeat, a useful intragenic marke r for SCA7 in segregation studies.