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A transcript map encompassing a susceptibility locus for bipolar affective disorder on chromosome 4q35

Molecular Psychiatry volume 7, pages 867–873 (2002)Cite this article

Abstract

Bipolar affective disorder is one of the most common mental illnesses with a population prevalence of approximately 1%. The disorder is genetically complex, with an increasing number of loci being implicated through genetic linkage studies. However, the specific genetic variations and molecules involved in bipolar susceptibility and pathogenesis are yet to be identified. Genetic linkage analysis has identified a bipolar disorder susceptibility locus on chromosome 4q35, and the interval harbouring this susceptibility gene has been narrowed to a size that is amenable to positional cloning. We have used the resources of the Human Genome Project (HGP) and Celera Genomics to identify overlapping sequenced BAC clones and sequence contigs that represent the region implicated by linkage analysis. A combination of bioinformatic tools and laboratory techniques have been applied to annotate this DNA sequence data and establish a comprehensive transcript map that spans approximately 5.5 Mb. This map encompasses the chromosome 4q35 bipolar susceptibility locus, which localises to a ‘most probable’ candidate interval of approximately 2.3 Mb, within a more conservative candidate interval of approximately 5 Mb. Localised within this map are 11 characterised genes and eight novel genes of unknown function, which together provide a collection of candidate transcripts that may be investigated for association with bipolar disorder. Overall, this region was shown to be very gene-poor, with a high incidence of pseudogenes, and redundant and novel repetitive elements. Our analysis of the interval has demonstrated a significant difference in the extent to which the current HGP and Celera sequence data sets represent this region.

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Acknowledgements

This study was supported by the National Health and Medical Research Council (Australia) via grants to the Garvan Institute of Medical Research (Block Grant 993050), the Mood Disorders Unit, Prince of Wales Hospital (Program Grant 993208), the Network of Brain Research into Mental Disorders (Unit Grant 983302), and by a research contract from Merck & Co and Merck Sharpe Dohme, Australia through PsyGene Pty Ltd, and by the New South Wales Health Department Infrastructure Grant Program.

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Authors and Affiliations

  1. Garvan Institute of Medical Research, Sydney, Australia

    I P Blair, L J Adams, R F Badenhop, M J Moses, A Scimone & P R Schofield

  2. Merck Research Laboratories, West Point, PA, USA

    J A Morris, L Ma & C P Austin

  3. Department of Biological Sciences, Macquarie University, Sydney, Australia

    J A Donald

  4. University of New South Wales, School of Psychiatry, and Prince of Wales Hospital, Mood Disorders Unit, Sydney, Australia

    R F Badenhop & P B Mitchell

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  1. I P Blair
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Correspondence to P R Schofield.

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Blair, I., Adams, L., Badenhop, R. et al. A transcript map encompassing a susceptibility locus for bipolar affective disorder on chromosome 4q35. Mol Psychiatry 7, 867–873 (2002). https://doi.org/10.1038/sj.mp.4001113

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