A 4-MEGABASE YAC CONTIG THAT SPANS THE LANGER-GIEDION SYNDROME REGIONON HUMAN-CHROMOSOME 8Q24.1 - USE IN REFINING THE LOCATION OF THE TRICHORHINOPHALANGEAL SYNDROME AND MULTIPLE EXOSTOSES GENES (TRPS1 AND EXT1)

We have constructed a physical map covering over 4 Mb of human chromos ome 8q24.1 and used this map to refine the locations of the genes resp onsible for Langer-Giedion syndrome. The map is composed of overlappin g YAC clones that were identified and ordered in relation to sequence tagged sites mapped to the Langer-Giedion chromosomal region on somati c cell hybrids. The minimal region of overlap of Langer-Giedion syndro me deletions, previously identified by analysis of 15 patients, was pl aced on the map by analysis of 2 patients whose deletions define the e ndpoints. The chromosome 8 breakpoint of a balanced t(8;9)(q24.11;q33. 3) translocation from a patient with trichorhinophalangeal syndrome (T RPS I) was found to be located just within the proximal end of the min imal deletion region. A deletion of 8q24.11-q24.3 in a patient with mu ltiple exostoses was found to overlap the distal end of the LGS deleti on region, indicating that the EXT1 gene is distal to the TRPS1 gene a nd supporting the hypothesis that Langer-Griedion syndrome is due to l oss of functional copies of both the TRPS1 and the EXT1 genes. (C) 199 5 Academic Press, Inc.