@article{5105779bee7643c1b2d13097f2759ac5,
title = "Evolutionary toggling of the MAPT 17q21.31 inversion region",
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.",
author = "Zody, {Michael C.} and Zhaoshi Jiang and Fung, {Hon Chung} and Francesca Antonacci and Hillier, {La Deana W.} and Cardone, {Maria Francesca} and Graves, {Tina A.} and Kidd, {Jeffrey M.} and Ze Cheng and Amr Abouelleil and Lin Chen and John Wallis and Jarret Glasscock and Wilson, {Richard K.} and Reily, {Amy Denise} and Jaime Duckworth and Mario Ventura and John Hardy and Warren, {Wesley C.} and Eichler, {Evan E.}",
note = "Funding Information: We thank T. Marques, D. Reich, A. Navarro, N. Patterson, S. McCarroll, T. Brown and K. Augustyn for critical comments and valuable discussions in the preparation of this manuscript; C. Alkan for providing computational assistance; and members of the Broad Institute Sequence Platform (BISP) and Washington University Genome Sequencing Center (WUGSC) for generating clone-based sequencing data for this project. M.C.Z., A.A., W.C.W., L.W.H., T.A.G., R.K.W., A.D.R., J.W., J.G. and the BISP and WUGSC were supported by grants from the National Human Genome Research Institute. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project number Z01 AG000957-05. This work was supported by NIH grants GM058815 and HG002385 to E.E.E. and a Rosetta Inpharmatics Fellowship (Merck Laboratories) to Z.J. E.E.E. is an investigator of the Howard Hughes Medical Institute.",
year = "2008",
month = sep,
doi = "10.1038/ng.193",
language = "English",
volume = "40",
pages = "1076--1083",
journal = "Nature Genetics",
issn = "1061-4036",
number = "9",
}