title: Analysis of amino-acid and nucleotide variants in the spinocerebellar ataxia type 1 (SCA1) gene in schizophrenic patients.
abstract: Several loci-containing genes that might harbour mutations predisposing to schizophrenia have recently been identified. The locus on chromosome 6p has been detected by several groups and appears to predispose to schizophrenia in 15%-30% of the pedigrees in one of these studies. The chromosome 6p locus for schizophrenia spans about 30 cM, between markers D6S296 and D6S276. The current transcription map of the 6p22-24 region includes three expressed sequence tags and six genes, one of which is the spinocerebellar ataxia type 1 (SCA1) gene. Patients with SCA1 have the CAG repeat sequence, which encodes a polyglutamine stretch in the ataxin-1 protein, expanded beyond the normal range. More recently, linkage disequilibrium between schizophrenia and the SCA1 CAG repeat has been reported. SCA1 is a good candidate gene for the schizophrenia-susceptibility locus on chromosome 6p as indicated by its expression pattern. We have studied the coding region of the SCA1 gene (exons 8 and 9) in samples from schizophrenia patients and have identified two amino-acid variants (S186C and P754S) and three nucleotide polymorphisms (1409A/G, 1865T/C and 2150A/G). One of the amino-acid changes (S186C) 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 population. S186C and other variants may be of relevance to the complex genetic factors involved in schizophrenia phenotypes.
authors.affiliation: Cancer Research Institute, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Pujana
authors.forename: L
authors.initials: L
authors.lastname: Martorell
authors.forename: V
authors.initials: V
authors.lastname: Volpini
authors.forename: J
authors.initials: J
authors.lastname: Valero
authors.forename: A
authors.initials: A
authors.lastname: Labad
authors.forename: E
authors.initials: E
authors.lastname: Vilella
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000483:Alleles; D000596:Amino Acids / Q000032:analysis / Q000235:genetics*; D000067696:Ataxin-1; D000067528:Ataxins; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D009711:Nucleotides / Q000032:analysis*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018911:Trinucleotide Repeats
chemical_list: C000593749:ATXN1 protein, human; D000596:Amino Acids; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009711:Nucleotides