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Human Genetics

, Volume 100, Issue 1, pp 114–122 | Cite as

cDNAs with long CAG trinucleotide repeats from human brain

  • Russell L. Margolis
  • Meena R. Abraham
  • Shawn B. Gatchell
  • Shi-Hua Li
  • Arif S. Kidwai
  • Theresa S. Breschel
  • O. Colin Stine
  • Colleen Callahan
  • Melvin G. McInnis
  • Christopher A. Ross
Original investigation

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.

Keywords

Trinucleotide Repeat Spinocerebellar Ataxia Bipolar Affective Disorder Glutamine Residue Fetal Human Brain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Russell L. Margolis
    • 1
  • Meena R. Abraham
    • 1
  • Shawn B. Gatchell
    • 1
  • Shi-Hua Li
    • 1
  • Arif S. Kidwai
    • 1
  • Theresa S. Breschel
    • 1
  • O. Colin Stine
    • 1
  • Colleen Callahan
    • 1
  • Melvin G. McInnis
    • 1
  • Christopher A. Ross
    • 1
  1. 1.Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USATP

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