title: Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder.
abstract: The gene for the synaptic vesicle docking fusion protein, synaptosomal-associated protein of 25 kDa (SNAP-25), has been implicated in the etiology of attention-deficit hyperactivity disorder (ADHD) based on the mouse mutant strain coloboma. This neutron-irradiation induced mouse strain is hemizygous for the deletion of the SNAP-25 gene and displays spontaneous hyperactivity that is responsive to dextroamphetamine. Because of these characteristics, this strain has been suggested to be a mouse model for ADHD. We identified using single stranded conformational polymorphism analysis (SSCP) four DNA sequence variants in the 3' untranslated region of the human SNAP-25 gene. We searched for polymorphisms in the 3' untranslated region because the intron/exon structure of this gene has not yet been determined. We tested for linkage of this gene and ADHD using two of the identified polymorphisms that change a restriction enzyme recognition site. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test in a sample of 97 small nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We observed biased transmission of the haplotypes of the alleles of these two polymorphisms. Our findings are suggestive of a role of this gene in ADHD.
authors.affiliation: Department of Psychiatry, The Toronto Hospital, Western Division, Canada. CBarr@playfair.utoronto.ca
authors.forename: C L
authors.initials: CL
authors.lastname: Barr
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: K
authors.initials: K
authors.lastname: Wigg
authors.forename: S
authors.initials: S
authors.lastname: Bloom
authors.forename: W
authors.initials: W
authors.lastname: Roberts
authors.forename: M
authors.initials: M
authors.lastname: Malone
authors.forename: R
authors.initials: R
authors.lastname: Schachar
authors.forename: R
authors.initials: R
authors.lastname: Tannock
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D006801:Humans; D015810:Linkage Disequilibrium; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D050825:Synaptosomal-Associated Protein 25
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25