HIGH-RESOLUTION PHYSICAL MAPPING OF A 6.7-MB YAC CONTIG SPANNING A REGION CRITICAL FOR THE MONOSOMY-21 PHENOTYPE IN 21Q21.3-Q22.1

Deletion of genes from the chromosome 21 region between APP and SOD1 i s a potential cause of some of the major phenotypic features of monoso my 21 patients, Fine physical mapping helps identify potential candida te genes, After selecting nonchimeric YACs by FISH analysis, we determ ined their marker contents by PCR and hybridization studies, Fifteen Y ACs were chosen and mapped by restriction enzyme analysis and labeling of end fragments. We localized 55 markers, including 31 STSs, 10 YAC ends, and 4 NotI linking clones, along a 6.7-Mb contig. This map facil itates transcriptional analysis of this region and construction of rea dy-to-sequence contigs, Furthermore, FISH mapping of two patients with partial monosomy 21 using YAC and cosmid clones allowed us to define more accurately the telomeric border of the critical region between ma rkers S226 and S213. (C) 1997 Academic Press.