4.5-Mb YAC STS contig at 50-kb resolution, spanning Xq25 deletions in two patients with lymphoproliferative syndrome

Sequence-tagged site (STS) content mapping in yeast artificial chromosomes (YACs) was used to cover the region deleted in two patients affected with X-linked lymphoproliferative disorder. The order of markers includes, centromere to telomere, DXS8009-DXS1206-DXS8078-DXS8044-DXS982-DXS6811-DXS8093-AFM240xb10-DXS75-DXS737-DXS100-DXS6-DXS1046-DXS8038. The order of six major markers is confirmed by fluorescent in situ hybridization, and all the markers assigned by linkage mapping fall within a 1.6-cM interval. The contig comprises 90 clones containing 89 STSs, yielding a resolution of 50 kb; DNA in a gap just telomeric to DXS8044 has not been found in >20 equivalents of YACs or bacterial clones. The two deletions were found to have centromeric breakpoints that lie close to DXS1206 and may be identical; the telomeric breakpoints are similar to 150 kb apart, one falling between DXS737 and DXS100, the other between DXS100 and DXS1046. Several STSs near the breakpoints show weak amplification from more than one site; one gives products from three groups of YACs, and lie, respectively, within 50 kb of the centromeric and the two telomeric deletion borders. Such partially duplicated segments of DNA are candidates for involvement in the formation of the deletions.