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Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner

Simone de Jong123, Iouri Chepelev4, Esther Janson1, Eric Strengman13, Leonard H van den Berg5, Jan H Veldink5 and Roel A Ophoff23*

Author Affiliations

1 Department of Medical Genetics, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands

2 Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, 3508 GA, The Netherlands

3 Center for Neurobehavioral Genetics, University of California Los Angeles, Box 951761, Gonda #4357C 695 Charles E. Young Drive South, Los Angeles, CA, 90095, USA

4 Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, MD, 20892, USA

5 Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands

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BMC Genomics 2012, 13:458  doi:10.1186/1471-2164-13-458

Published: 6 September 2012



Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry. Two divergent MAPT haplotypes, H1 and H2 are described with distinct linkage disequilibrium patterns across the region reflecting the inversion status at this locus. The MAPT H1 haplotype has been associated with progressive supranuclear palsy, corticobasal degeneration, Parkinson’s disease and Alzheimer’s disease, while the H2 is linked to recurrent deletion events associated with the 17q21.31 microdeletion syndrome, a disease characterized by developmental delay and learning disability.


In this study, we investigate the effect of the inversion on the expression of genes in the 17q21.31 region. We find the expression of several genes in and at the borders of the inversion to be affected; specific either to whole blood or different regions of the human brain. The H1 haplotype was found to be associated with an increased expression of LRRC37A4, PLEKH1M and MAPT. In contrast, a decreased expression of MGC57346, LRRC37A and CRHR1 was associated with H1.


Studies thus far have focused on the expression of MAPT in the inversion region. However, our results show that the inversion status affects expression of other genes in the 17q21.31 region as well. Given the link between the inversion status and different neurological diseases, these genes may also be involved in disease pathology, possibly in a tissue-specific manner.