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Genetics

The MAPT locus—a genetic paradigm in disease susceptibility

Nature Reviews Neurology volume 8, pages 477–478 (2012)Cite this article

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Understanding how genetic variation can confer susceptibility to neurological disease is an urgent priority. A new gene-expression study has explored the relationship between DNA sequence variation at the microtubule-associated protein tau (MAPT) locus and MAPT expression in the brain, providing an exciting new paradigm for the field.

To understand the genetic basis of neurological disease, we must better understanding how expression and splicing of disease-associated genes is regulated. Studies to resolve these issues should be done not in diseased brain tissue but in healthy postmortem brain tissue, as this approach will enable the association of genetic variation with alterations in gene expression to be determined without the confounding effects of disease pathology. In a recent study, published in Human Molecular Genetics, Daniah Trabzuni, Mina Ryten and colleagues analysed the expression of microtubule-associated protein tau (MAPT) mRNA in 2,011 brain regions from human postmortem brain tissue obtained from 439 healthy individuals.1 Expression data from ten distinct brain regions, including the hippocampus, cortex, substantia nigra and white matter, were assessed to determine the variation in MAPT expression across these regions and understand how genetic haplotypes at this locus affect gene expression and splicing.

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Figure 1: The MAPT gene locus and the tau protein isoforms.

References

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Acknowledgements

Work in the Wade-Martins laboratory has been supported by Alzheimer's Research UK, Cure PSP, The Wellcome Trust and the Monument Trust Discovery Award from Parkinson's UK.

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  1. Department of Physiology, Oxford Parkinson's Disease Centre, Anatomy and Genetics, Le Gros Clark Building, South Parks Road, University of Oxford, Oxford, OX1 3QX, UK

    Richard Wade-Martins

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Wade-Martins, R. The MAPT locus—a genetic paradigm in disease susceptibility. Nat Rev Neurol 8, 477–478 (2012). https://doi.org/10.1038/nrneurol.2012.169

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