A complete physical contig and partial transcript map of the Williams syndrome critical region

Williams syndrome (WS) is a contiguous gene syndrome caused by hemizygosity for a chromosomal deletion at 7q11.23. The range of phenotypes includes me ntal retardation, dysmorphic facies, heart abnormalities, short stature, a specific cognitive profile, hyperacusis, and infantile hypercalcaemia. To i dentify all the deleted genes, we have constructed a detailed physical map and complete BAC/PAC contig of the critical region, extending a distance of approximately 2 Mb and delimited by the nondeleted markers D7S1816 and D7S 489A. Somatic cell hybrids of WS patients were made and used to define the centromeric and telomeric deletion breakpoints, enabling the size of the WS deletion to be defined as approximately 1.4 Mb. Genes previously mapped to the region have been located on the contig, and we have isolated eight tra nscripts, two of which have been characterized as the genes CPETR1 and CPET R2. This contig and expressed sequence map will form the basis for the cons truction of a complete transcription map of the deleted region and will ena ble genotype-phenotype correlations to be attempted to identify the individ ual components of WS. (C) 1999 Academic Press.