Breakpoint analysis of human chromosome 3 inversions during hominoid evolution

Abstract

Comparative fluorescence in situ hybridization (FISH) mapping revealed four large DNA segments which have been conserved in their entirety between human chromosome 3 and Bornean orangutan chromosome 2 as well as three evolutionary breakpoints which distinguish between the human and Bornean orangutan chromosome forms. Examination of the structural and functional features of evolutionary breakpoints provides new insights into the possible effects of evolutionary rearrangements on genome function and the relationship between human chromosome pathology and evolution. FISH of human BAC clones which were assesssed in human genomic sequence to primate chromosomes, combined with precise breakpoint localizations by polymerase chain reaction (PCR) analysis of flow-sorted chromosomes and in silico analysis, were used to characterize the evolutionary breakpoints. None of the three breakpoints studied disrupts a validated gene(s), however they are all associated with segmental duplications. At least eleven DNA segments (&a