Characterization of the human lineage-specific pericentric inversion that distinguishes human chromosome 1 from the homologous chromosomes of the great apes.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Szamalek, Justyna M; Goidts, Violaine; Cooper, David N; Hameister, Horst; Kehrer-Sawatzki, Hildegard
Year of Publication: 2006
Journal: Hum Genet
Volume: 120
Issue: 1
Pagination: 126-38
Date Published: 2006 Aug
Publication Language: eng
ISSN: 0340-6717
Keywords: Animals, Cell Line, Cell Lineage, Centromere, Chromosome Breakage, Chromosome Inversion, Chromosomes, Human, Pair 1, Evolution, Molecular, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Pan troglodytes, Synteny

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.

DOI: 10.1007/s00439-006-0209-y
Alternate Journal: Hum. Genet.