YAC CONTIGS FOR 4Q35 IN THE REGION OF THE FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY (FSHD) GENE

We report here the construction of a genetic linkage map and an overla pping set of clones containing DNA markers linked to the causative loc us for facioscapulohumeral muscular dystrophy (FSHD) on 4q35. Multipoi nt linkage analysis placed eight loci in the following order with odds greater than 1000:1: I-D4S426-D4S187-D4S130-D4S163-D4S139-D4F35S1-qte r. The most likely position of D4S809 was distal to D4F35S1. Thirty-fo ur yeast artificial chromosomes (YACs) were isolated by PCR-based assa ys for STSs derived from DNA markers with known genetic and physical o rder. Walking from the insert ends of 2 YACs identified 7 additional Y ACs, bridging the gaps between three of the markers. Two new YACs were found by hybridization of a cosmid inter-Alu PCR product to dot blots of inter-Alu PCR products of PAC DNA pools. All YAC clones were posit ioned using the genetic and physical order of the STSs and inter-Alu P CR fingerprint data. Eleven of the YACs and two cosmids were mapped by fluorescence in situ hybridization to confirm the location of the clo nes and to detect chimerism. The 43 YACs were assembled into two conti gs. The larger contig spans approximately 2.4 Mb and contains markers closest to the FSHD gene. (C) 1994 Academic Press, Inc.