Many genomic disorders occur as a result of chromosome rearrangements involving 
low-copy repeats (LCRs). To better understand the molecular basis of chromosome 
rearrangements, including translocations, we have investigated the mechanism of 
evolutionary rearrangements. In contrast to several intrachromosomal 
rearrangements, only two evolutionary translocations have been identified by 
cytogenetic analyses of humans and greater apes. Human chromosome 2 arose as a 
result of a telomeric fusion between acrocentric chromosomes, whereas 
chromosomes 4 and 19 in Gorilla gorilla are the products of a reciprocal 
translocation between ancestral chromosomes, syntenic to human chromosomes 5 and 
17, respectively. Fluorescence in situ hybridization (FISH) was used to 
characterize the breakpoints of the latter translocation at the molecular level. 
We identified three BAC clones that span translocation breakpoints. One 
breakpoint occurred in the region syntenic to human chromosome 5q13.3, between 
the HMG-CoA reductase gene (HMGCR) and RAS p21 protein activator 1 gene (RASA1). 
The second breakpoint was in a region syntenic to human chromosome 17p12 
containing the 24 kb region-specific low-copy repeat-proximal CMT1A-REP. 
Moreover, we found that the t(4;19) is associated with a submicroscopic 
chromosome duplication involving a 19p chromosome fragment homologous to the 
human chromosome region surrounding the proximal CMT1A-REP. These observations 
further indicate that higher order genomic architecture involving low-copy 
repeats resulting from genomic duplication plays a significant role in 
karyotypic evolution.