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Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder

Molecular Psychiatry volume 6, pages 694–700 (2001)Cite this article

Abstract

Chromosome 22 has been implicated in schizophrenia and bipolar disorder in a number of linkage, association and cytogenetic studies. Recent evidence has also implicated CAG repeat tract expansion in these diseases. In order to explore the involvement of CAG repeats on chromosome 22 in these diseases, we have created an integrated map of all CAG repeats ≥5 on this chromosome together with microsatellite markers associated with these diseases using the recently completed nucleotide sequence of chromosome 22. Of the 52 CAG repeat loci identified in this manner, four of the longest repeat stretches in regions previously implicated by linkage analyses were chosen for further study. Three of the four repeat containing loci, were found in the coding region with the CAG repeats coding for glutamine and were expressed in the brain. All the loci studied showed varying degrees of polymorphism with one of the loci exhibiting two alleles of 7 and 8 CAG repeats. The 8-repeat allele at this locus was significantly overrepresented in both schizophrenia and bipolar patient groups when compared to ethnically matched controls, while alleles at the other three loci did not show any such difference. The repeat lies within a gene which shows homology to an androgen receptor related apoptosis protein in rat. We have also identified other candidate genes in the vicinity of this locus. Our results suggest that the repeats within this gene or other genes in the vicinity of this locus are likely to be implicated in bipolar disorder and schizophrenia.

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Acknowledgements

We are grateful to Ms B Sujatha and Dr Vani Brahmachari for providing some of the normal DNA samples, Ms R Jaya and Ms M Ruchi for help with Genescan analysis, Mr Neeraj Pandey for providing primers for the 22CH4 locus, Dr CB Rao and Professor DK Subbukrishna for assistance with statistical analyses. We would like to acknowledge Dr Anuranjan Anand for extraction of patient DNA samples. This work was supported by Dept of Biotechnology, Govt of India and Council of Scientific and Industrial Research, Govt of India.

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Authors and Affiliations

  1. Functional Genomics Unit, Centre for Biochemical Technology (CSIR), Mall Rd, Delhi University Campus, Delhi, 110 007, India

    Q Saleem, D Dash & S K Brahmachari

  2. Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, Karnataka, India

    Q Saleem & S K Brahmachari

  3. Dept of Psychiatry, National Institute of Mental Health and Neurosciences, Hosur Rd, Bangalore, 560 029, India

    C Gandhi, A Kishore, V Benegal, T Sherrin, O Mukherjee & S Jain

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  1. Q Saleem
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Correspondence to S K Brahmachari.

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Saleem, Q., Dash, D., Gandhi, C. et al. Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder. Mol Psychiatry 6, 694–700 (2001). https://doi.org/10.1038/sj.mp.4000924

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