ANALYSIS OF AMINO-ACID AND NUCLEOTIDE VARIANTS IN THE SPINOCEREBELLARATAXIA TYPE-1 (SCA1) GENE IN SCHIZOPHRENIC-PATIENTS

Several loci-containing genes that might harbour mutations predisposin g to schizophrenia have recently been identified. The locus on chromos ome 6p has been detected by several groups and appears to predispose t o schizophrenia in 15%-30% of the pedigrees in one of these studies. T he chromosome 6p locus for schizophrenia spans about 30 cM, between ma rkers D6S296 and D6S276. The current transcription map of the 6p22-24 region includes three expressed sequence tags and six genes, one of wh ich is the spinocerebellar ataxia type 1 (SCA1) gene. Patients with SC A1 have the CAG repeat sequence, which encodes a polyglutamine stretch in the ataxin-1 protein, expanded beyond the normal range. More recen tly, linkage disequilibrium between schizophrenia and the SCA1 CAG rep eat has been reported. SCA1 is a good candidate gene for the schizophr enia-susceptibility locus on chromosome 6p as indicated by its express ion pattern. We have studied the coding region of the SCA1 gene (exons 8 and 9) in samples from schizophrenia patients and have identified t wo amino-acid variants (S186C and P754S) and three nucleotide polymorp hisms (1409A/G, 1865T/C and 2150A/G). One of the amino-acid changes (S 186C) was present in two schizophrenic brothers from one family and in a schizophrenic patient and a non-affected subject of a second family but it was not detected in 100 unrelated subjects from the general po pulation. S186C and other variants may be of relevance to the complex genetic factors involved in schizophrenia phenotypes.