title: cDNAs with long CAG trinucleotide repeats from human brain.
abstract: Twelve diseases, most with neuropsychiatric features, arise from trinucleotide repeat expansion mutations. Expansion mutations may also cause a number of other disorders, including several additional forms of spinocerebellar ataxia, bipolar affective disorder, schizophrenia, and autism. To obtain candiate genes for these disorders, cDNA libraries from adult and fetal human brain were screened at high stringency for clones containing CAG repeats. Nineteen cDNAs were isolated and mapped to chromosomes 1, 2, 4, 6, 7, 8, 9, 12, 16, 19, 20, and X. The clones contain between 4 and 17 consecutive CAG, CTG, TCG, or GCA triplets. Clone H44 encodes 40 consecutive glutamines, more than any other entry in the nonredundant GenBank protein database and well within the range that causes neuronal degeneration in several of the glutamine expansion diseases. Eight cDNAs encode 15 or more consecutive glutamine residues, suggesting that the gene products may function as transcription factors, with a potential role in the regulation of neurodevelopment or neuroplasticity. In particular, the conceptual translation of clone CTG3a contains 18 consecutive glutamines and is 45% identical to the C-terminal 306 residues of the mouse numb gene product. These genes are therefore candidates for diseases featuring anticipation, neurodegeneration, or abnormalities of neurodevelopment.
authors.affiliation: Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. rmargoli@welchlink.welch.jhu.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Margolis
authors.forename: M R
authors.initials: MR
authors.lastname: Abraham
authors.forename: S B
authors.initials: SB
authors.lastname: Gatchell
authors.forename: S H
authors.initials: SH
authors.lastname: Li
authors.forename: A S
authors.initials: AS
authors.lastname: Kidwai
authors.forename: T S
authors.initials: TS
authors.lastname: Breschel
authors.forename: O C
authors.initials: OC
authors.lastname: Stine
authors.forename: C
authors.initials: C
authors.lastname: Callahan
authors.forename: M G
authors.initials: MG
authors.lastname: McInnis
authors.forename: C A
authors.initials: CA
authors.lastname: Ross
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D005333:Fetus; D005625:Frontal Lobe / Q000737:chemistry*; D015723:Gene Library; D006579:Heterozygote; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D001523:Mental Disorders / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010455:Peptides / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D018911:Trinucleotide Repeats
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; D010455:Peptides; C097188:polyglutamine