Comparative maps of human 19p13.3 and mouse chromosome 10 allow identification of sequences at evolutionary breakpoints

A cosmid/bacterial artificial chromosome (BAC) contiguous (contig) map of h uman chromosome (HSA) 19p13.3 has been constructed, and over 50 genes have been localized to the contig. Genes and anonymous ESTs from approximate to 4000 kb of human 19p13.3 were placed on the central mouse chromosome 10 map by genetic mapping and pulsed-field gel electrophoresis (PFGE) analysis. A region of similar to 2500 kb of HSA 19p13.3 is collinear to mouse chromoso me (MMU) 10. In contrast, the adjacent approximate to 1200 kb are inverted. Two genes are located in a 50-kb region after the inversion on MMU 10, fol lowed by a region of homology to mouse chromosome 17. The synteny breakpoin t and one of the inversion breakpoints has been localized to sequenced regi ons in human <5 kb in size. Both breakpoints are rich in simple tandem repe ats, including (TCTG)n, (CT)n, and (GTCTCT)n, suggesting that simple repeat sequences may be involved in chromosome breaks during evolution. The overa ll size of the region in mouse is smaller, although no large regions are mi ssing. Comparing the physical maps to the genetic maps showed that in contr ast to the higher-than-average rate of genetic recombination in gene-rich t elomeric region on HSA 19p33.3, the average rate of recombination is lower than expected in the homologous mouse region. This might indicate that a ho t spot of recombination may have been lost in mouse or gained in human duri ng evolution, or that the position of sequences along the chromosome (telom eric compared to the middle of a chromosome) is important for recombination rates.