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. 1996 Oct;59(4):912–917.

Expansion of 50 CAG/CTG repeats excluded in schizophrenia by application of a highly efficient approach using repeat expansion detection and a PCR screening set.

T Bowen 1, C Guy 1, G Speight 1, L Jones 1, A Cardno 1, K Murphy 1, P McGuffin 1, M J Owen 1, M C O'Donovan 1
PMCID: PMC1914801  PMID: 8808608

Abstract

Studies of the transmission of schizophrenia in families with affected members in several generations have suggested that an expanded trinucleotide repeat mechanism may contribute to the genetic inheritance of this disorder. Using repeat expansion detection (RED), we and others have previously found that the distribution of CAG/CTG repeat size is larger in patients with schizophrenia than in controls. In an attempt to identify the specific expanded CAG/CTG locus or loci associated with schizophrenia, we have now used an approach based on a CAG/CTG PCR screening set combined with RED data. This has allowed us to minimize genotyping while excluding 43 polymorphic autosomal loci and 7 X-chromosomal loci from the screening set as candidates for expansion in schizophrenia with a very high degree of confidence.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Haaf T., Sirugo G., Kidd K. K., Ward D. C. Chromosomal localization of long trinucleotide repeats in the human genome by fluorescence in situ hybridization. Nat Genet. 1996 Feb;12(2):183–185. doi: 10.1038/ng0296-183. [DOI] [PubMed] [Google Scholar]
  2. Kawaguchi Y., Okamoto T., Taniwaki M., Aizawa M., Inoue M., Katayama S., Kawakami H., Nakamura S., Nishimura M., Akiguchi I. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. 1994 Nov;8(3):221–228. doi: 10.1038/ng1194-221. [DOI] [PubMed] [Google Scholar]
  3. Margolis R. L., Stine O. C., McInnis M. G., Ranen N. G., Rubinsztein D. C., Leggo J., Brando L. V., Kidwai A. S., Loev S. J., Breschel T. S. cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat. Hum Mol Genet. 1996 May;5(5):607–616. doi: 10.1093/hmg/5.5.607. [DOI] [PubMed] [Google Scholar]
  4. McGuffin P., Farmer A., Harvey I. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch Gen Psychiatry. 1991 Aug;48(8):764–770. doi: 10.1001/archpsyc.1991.01810320088015. [DOI] [PubMed] [Google Scholar]
  5. McGuffin P., Owen M. J., Farmer A. E. Genetic basis of schizophrenia. Lancet. 1995 Sep 9;346(8976):678–682. doi: 10.1016/s0140-6736(95)92285-7. [DOI] [PubMed] [Google Scholar]
  6. Morris A. G., Gaitonde E., McKenna P. J., Mollon J. D., Hunt D. M. CAG repeat expansions and schizophrenia: association with disease in females and with early age-at-onset. Hum Mol Genet. 1995 Oct;4(10):1957–1961. doi: 10.1093/hmg/4.10.1957. [DOI] [PubMed] [Google Scholar]
  7. Morrison P. J. Trinucleotide repeat repeat repeat. Lancet. 1993 Aug 14;342(8868):385–386. doi: 10.1016/0140-6736(93)92809-8. [DOI] [PubMed] [Google Scholar]
  8. O'Donovan M. C., Guy C., Craddock N., Murphy K. C., Cardno A. G., Jones L. A., Owen M. J., McGuffin P. Expanded CAG repeats in schizophrenia and bipolar disorder. Nat Genet. 1995 Aug;10(4):380–381. doi: 10.1038/ng0895-380. [DOI] [PubMed] [Google Scholar]
  9. O'Donovan M. C., Owen M. J. Dynamic mutations and psychiatric genetics. Psychol Med. 1996 Jan;26(1):1–6. doi: 10.1017/s0033291700033663. [DOI] [PubMed] [Google Scholar]
  10. Schalling M., Hudson T. J., Buetow K. H., Housman D. E. Direct detection of novel expanded trinucleotide repeats in the human genome. Nat Genet. 1993 Jun;4(2):135–139. doi: 10.1038/ng0693-135. [DOI] [PubMed] [Google Scholar]
  11. Stallings R. L. Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence: implications for human genetic diseases. Genomics. 1994 May 1;21(1):116–121. doi: 10.1006/geno.1994.1232. [DOI] [PubMed] [Google Scholar]
  12. Vincent J. B., Klempan T., Parikh S. S., Sasaki T., Meltzer H. Y., Sirugo G., Cola P., Petronis A., Kennedy J. L. Frequency analysis of large CAG/CTG trinucleotide repeats in schizophrenia and bipolar affective disorder. Mol Psychiatry. 1996 May;1(2):141–148. [PubMed] [Google Scholar]
  13. Wing J. K., Babor T., Brugha T., Burke J., Cooper J. E., Giel R., Jablenski A., Regier D., Sartorius N. SCAN. Schedules for Clinical Assessment in Neuropsychiatry. Arch Gen Psychiatry. 1990 Jun;47(6):589–593. doi: 10.1001/archpsyc.1990.01810180089012. [DOI] [PubMed] [Google Scholar]
  14. Xu Y., Mural R. J., Uberbacher E. C. Correcting sequencing errors in DNA coding regions using a dynamic programming approach. Comput Appl Biosci. 1995 Apr;11(2):117–124. doi: 10.1093/bioinformatics/11.2.117. [DOI] [PubMed] [Google Scholar]

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