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The dystrobrevin-binding protein 1 gene: features and networks

Molecular Psychiatry volume 14, pages 18–29 (2009)Cite this article

Abstract

The dystrobrevin-binding protein 1 (DTNBP1) gene has been one of the most studied and promising schizophrenia susceptibility genes since it was first reported to be associated with schizophrenia in the Irish Study of High Density Schizophrenia Families (ISHDSF). Although many studies have been performed both at the functional level and in association with psychiatric disorders, there has been no systematic review of the features of the DTNBP1 gene, protein or the relationship between function and phenotype. Using a bioinformatics approach, we identified the DTNBP1 gene in 13 vertebrate species. The comparison of these genes revealed a conserved gene structure, protein-coding sequence and dysbindin domain, but a diverse noncoding sequence. The molecular evolutionary analysis suggests the DTNBP1 gene probably originated in chordates and matured in vertebrates. No signature of recent positive selection was seen in any primate lineage. The DTNBP1 gene likely has many more alternative transcripts than the current three major isoforms annotated in the NCBI database. Our examination of risk haplotypes revealed that, although the frequency of a single nucleotide polymorphism (SNP) or haplotype might be significantly different in cases from controls, difference between major geographic populations was even larger. Finally, we constructed the first DTNBP1 interactome and explored its network features. Besides the biogenesis of lysosome-related organelles complex 1 and dystrophin-associated protein complex, several molecules in the DTNBP1 network likely provide insight into the role of DTNBP1 in biological systems: retinoic acid, β-estradiol, calmodulin and tumour necrosis factor. Studies of these subnetworks and pathways may provide opportunities to deepen our understanding of the mechanisms of action of DTNBP1 variants.

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Acknowledgements

We regret that many DTNBP1 studies, especially association studies, have not been cited in this review because of our focus on gene feature and network analysis. This work was supported by a NARSAD Young Investigator Award and a Jeffress Trust grant to ZZ and a research grant (R01MH41953) to KSK/BPR.

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  1. A Y Guo and J Sun: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA

    A Y Guo, J Sun, B P Riley, D L Thiselton, K S Kendler & Z Zhao

  2. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA

    B P Riley, K S Kendler & Z Zhao

  3. Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA, USA

    Z Zhao

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  1. A Y Guo
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Correspondence to Z Zhao.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Guo, A., Sun, J., Riley, B. et al. The dystrobrevin-binding protein 1 gene: features and networks. Mol Psychiatry 14, 18–29 (2009). https://doi.org/10.1038/mp.2008.88

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