title: Search for unstable DNA in schizophrenia families with evidence for genetic anticipation.
abstract: Evidence for genetic anticipation has recently become an important subject of research in clinical psychiatric genetics. Renewed interest in anticipation was evoked by molecular genetic findings of a novel type of mutation termed "unstable DNA." The unstable DNA model can be construed as the "best fit" for schizophrenia twin and family epidemiological data. We have performed a large-scale Southern blot hybridization, asymmetrical PCR-based, and repeat expansion-detection screening for (CAG)n/(CTG)n and (CCG)n/(CGG)n expansions in eastern Canadian schizophrenia multiplex families demonstrating genetic anticipation. There were no differences in (CAG)n/(CTG)n and (CCG)n/(CGG)n pattern distribution either between affected and unaffected individuals or across generations. Our findings do not support the hypothesis that large (CAG)n/(CTG)n or (CCG)n/(CGG)n expansions are the major etiologic factor in schizophrenia. A separate set of experiments directed to the analysis of small (30-130 trinucleotides), Huntington disease-type expansions in individual genes is required in order to fully exclude the presence of (CAG)n/(CTG)n- or (CCG)n/(CGG)n-type unstable mutation.
authors.affiliation: Neurogenetics Section, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Petronis
authors.forename: A S
authors.initials: AS
authors.lastname: Bassett
authors.forename: W G
authors.initials: WG
authors.lastname: Honer
authors.forename: J B
authors.initials: JB
authors.lastname: Vincent
authors.forename: Y
authors.initials: Y
authors.lastname: Tatuch
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: D J
authors.initials: DJ
authors.lastname: Ying
authors.forename: T A
authors.initials: TA
authors.lastname: Klempan
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D015139:Blotting, Southern; D004247:DNA / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: D004247:DNA