INTEGRATION OF PHYSICAL, BREAKPOINT AND GENETIC MAPS OF CHROMOSOME-22- LOCALIZATION OF 587 YEAST ARTIFICIAL CHROMOSOMES WITH 238 MAPPED MARKERS

Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying th e structure and function of the genome. We used data from STS content mapping of YACs and natural and induced chromosomal breakpoints to anc hor contigs of overlapping yeast artificial chromosome (YAC) clones sp anning extensive regions of human chromosome 22. The STSs were assigne d to specific regions (bins) on the chromosome using cell lines from a somatic hybrid mapping panel defining a maximum of 25 intervals. YAC libraries were screened by PCR amplification of hierarchical pools of yeast DNA with 238 markers, and a total of 587 YAC clones were identif ied. These YACs were assembled into contigs based upon their shared ST S content using a simulated annealing algorithm. Fifteen contigs, cont aining between 2 and 74 STSs were assembled, and ordered along the chr omosome based upon the cytogenetic breakpoint, meiotic and PFG maps. A dditional singleton YACs were assigned to unique chromesomal bins. The se ordered YAC contigs will be useful for identifying disease genes an d chromosomal breakpoints by positional cloning and will provide the f oundation for higher resolution physical maps for large scale sequenci ng of the chromosome.