cDNA cloning, expression profile and genomic structure of a novel human transcript on chromosome 10q24, and its analyses as a candidate gene for infantile onset spinocerebellar ataxia.

In our search for the disease gene underlying autosomally recessively inherited infantile onset spinocerebellar ataxia (IOSCA), we identified an expressed sequence tag cluster representing a previously uncharacterized transcript in the restricted genomic sequence covering the IOSCA locus on chromosome 10q24, and for mutation analyses in IOSCA patients isolated the corresponding novel human cDNA, C10orf6. Multiple tissue cDNA and Northern analyses showed that this gene is ubiquitously expressed, with expression levels highest in the skeletal muscle and less abundant in the brain, liver, and heart than in other tissues examined. C10orf6 consists of 20 exons forming a 7.3 kb cDNA which is capable of encoding a 1173 amino acid polypeptide and possesses orthologues in other mammals. Sequencing of RT and genomic PCR products of the gene revealed no alterations in IOSCA patients when compared to control subjects, and neither could differences be detected in expression levels between patient and control brain RNA samples, thus excluding mutation(s) in this novel gene as causative for IOSCA. However, this study facilitates future investigations on both the role of C10orf6 gene product in human cells as well as its possible involvement in the pathogenesis of other hereditary diseases mapped to chromosome 10q24.