Scientific Publications

Evolutionary toggling of the MAPT 17q21.31 inversion region.

Publication TypeJournal Article
AuthorsZody, MC, Jiang Z., Fung HC, Antonacci F., Hillier LW, Cardone MF, Graves TA, Kidd JM, Cheng Z., Abouelleil A., Chen L., Wallis J., Glasscock J., Wilson RK, Reily AD, Duckworth J., Ventura M., Hardy J., Warren WC, and Eichler EE
AbstractUsing 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.
Year of Publication2008
JournalNature genetics
Date Published (YYYY/MM/DD)2008/09/01
ISSN Number1061-4036