Evolutionary toggling of the MAPT 17q21.31 inversion region

Michael C. Zody, Zhaoshi Jiang, Hon Chung Fung, Francesca Antonacci, La Deana W. Hillier, Maria Francesca Cardone, Tina A. Graves, Jeffrey M. Kidd, Ze Cheng, Amr Abouelleil, Lin Chen, John Wallis, Jarret Glasscock, Richard K. Wilson, Amy Denise Reily, Jaime Duckworth, Mario Ventura, John Hardy, Wesley C. Warren, Evan E. Eichler

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126 Scopus citations


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.

Original languageEnglish
Pages (from-to)1076-1083
Number of pages8
JournalNature Genetics
Issue number9
StatePublished - Sep 2008


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