title: Characterization of the human lineage-specific pericentric inversion that distinguishes human chromosome 1 from the homologous chromosomes of the great apes.
abstract: The human and chimpanzee genomes are distinguishable in terms of ten gross karyotypic differences including nine pericentric inversions and a chromosomal fusion. Seven of these large pericentric inversions are chimpanzee-specific whereas two of them, involving human chromosomes 1 and 18, were fixed in the human lineage after the divergence of humans and chimpanzees. We have performed detailed molecular and computational characterization of the breakpoint regions of the human-specific inversion of chromosome 1. FISH analysis and sequence comparisons together revealed that the pericentromeric region of HSA 1 contains numerous segmental duplications that display a high degree of sequence similarity between both chromosomal arms. Detailed analysis of these regions has allowed us to refine the p-arm breakpoint region to a 154.2 kb interval at 1p11.2 and the q-arm breakpoint region to a 562.6 kb interval at 1q21.1. Both breakpoint regions contain human-specific segmental duplications arranged in inverted orientation. We therefore propose that the pericentric inversion of HSA 1 was mediated by intra-chromosomal non-homologous recombination between these highly homologous segmental duplications that had themselves arisen only recently in the human lineage by duplicative transposition.
authors.affiliation: Department of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Justyna M
authors.initials: JM
authors.lastname: Szamalek
authors.forename: Violaine
authors.initials: V
authors.lastname: Goidts
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Horst
authors.initials: H
authors.lastname: Hameister
authors.forename: Hildegard
authors.initials: H
authors.lastname: Kehrer-Sawatzki
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D002503:Centromere / Q000235:genetics; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping; D002679:Pan troglodytes / Q000235:genetics*; D026801:Synteny