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.
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Zody
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Jiang
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonacci
authors.forename: LaDeana W
authors.initials: LW
authors.lastname: Hillier
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Cardone
authors.forename: Tina A
authors.initials: TA
authors.lastname: Graves
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.forename: Ze
authors.initials: Z
authors.lastname: Cheng
authors.forename: Amr
authors.initials: A
authors.lastname: Abouelleil
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Wallis
authors.forename: Jarret
authors.initials: J
authors.lastname: Glasscock
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: Amy Denise
authors.initials: AD
authors.lastname: Reily
authors.forename: Jaime
authors.initials: J
authors.lastname: Duckworth
authors.forename: Mario
authors.initials: M
authors.lastname: Ventura
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Warren
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D000818:Animals; D001483:Base Sequence; D007446:Chromosome Inversion; D002886:Chromosomes, Human, Pair 17; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011148:Pongo pygmaeus / Q000235:genetics; D017422:Sequence Analysis, DNA; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins