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Nat Genet DOI:10.1038/ng.193

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

Publication TypeJournal Article
Year of Publication2008
AuthorsZody, MC, Jiang, Z, Fung, H-C, Antonacci, F, Hillier, LDW, Cardone, MFrancesca, Graves, TA, Kidd, JM, Cheng, Z, Abouelleil, A, Chen, L, Wallis, J, Glasscock, J, Wilson, RK, Reily, ADenise, Duckworth, J, Ventura, M, Hardy, J, Warren, WC, Eichler, EE
JournalNat Genet
Date Published2008 Sep
KeywordsAnimals, Base Sequence, Chromosome Inversion, Chromosomes, Human, Pair 17, Evolution, Molecular, Gene Duplication, Humans, Models, Biological, Molecular Sequence Data, Pan troglodytes, Phylogeny, Polymorphism, Genetic, Pongo pygmaeus, Sequence Analysis, DNA, tau Proteins

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.


Alternate JournalNat. Genet.
PubMed ID19165922
PubMed Central IDPMC2684794
Grant ListR01 GM058815-08 / GM / NIGMS NIH HHS / United States
R01 GM058815 / GM / NIGMS NIH HHS / United States
G0701075 / / Medical Research Council / United Kingdom
GM058815 / GM / NIGMS NIH HHS / United States
HG002385 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R01 HG002385-08 / HG / NHGRI NIH HHS / United States
R01 HG002385 / HG / NHGRI NIH HHS / United States
Z01 AG000957 / AG / NIA NIH HHS / United States
Z01 AG000957-05 / / Intramural NIH HHS / United States
Z01 AG000957-05 / AG / NIA NIH HHS / United States