Article abstract
Nature Genetics 40, 1076 - 1083 (2008)
Published online: 10 August 2008 | Corrected online: 17 August 2008 | doi:10.1038/ng.193
Evolutionary toggling of the MAPT 17q21.31 inversion region
Michael C Zody1,2,9, Zhaoshi Jiang3,9, Hon-Chung Fung4,5, Francesca Antonacci3, LaDeana W Hillier6, Maria Francesca Cardone7, Tina A Graves6, Jeffrey M Kidd3, Ze Cheng3, Amr Abouelleil1, Lin Chen3, John Wallis6, Jarret Glasscock6, Richard K Wilson6, Amy Denise Reily6, Jaime Duckworth8, Mario Ventura7, John Hardy4, Wesley C Warren6 & Evan E Eichler3
Abstract
Using comparative sequencing approaches, we investigated the evolutionary history of the European-enriched 17q21.31 MAPT inversion polymorphism. We present a detailed, BAC-based sequence assembly of the inverted human H2 haplotype and compare it to the sequence structure and genetic variation of the corresponding 1.5-Mb region for the noninverted H1 human haplotype and that of chimpanzee and orangutan. We found that inversion of the MAPT region is similarly polymorphic in other great ape species, and we present evidence that the inversions occurred independently in chimpanzees and humans. In humans, the inversion breakpoints correspond to core duplications with the LRRC37 gene family. Our analysis favors the H2 configuration and sequence haplotype as the likely great ape and human ancestral state, with inversion recurrences during primate evolution. We show that the H2 architecture has evolved more extensive sequence homology, perhaps explaining its tendency to undergo microdeletion associated with mental retardation in European populations.
- Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
- Department of Medical Biochemistry and Microbiology, Uppsala University, Box 597, Uppsala SE-751 24, Sweden.
- Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
- Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, London WC1N 3BG, UK.
- Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199 Tung Hwa North Road, Taipei 10591, Taiwan.
- Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St. Louis, Missouri 63108, USA.
- Department of Genetics and Microbiology, University of Bari, Via Amendola 165/A, Bari 70126, Italy.
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
- These authors contributed equally to this work.
Correspondence to: Evan E Eichler3 e-mail: eee@gs.washington.edu
Correspondence to: Wesley C Warren6 e-mail: wwarren@watson.wustl.edu
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