Construction of a physical and transcript map for a 1-Mb genomic region containing the urofacial (Ochoa) syndrome gene on 10q23-q24 and localization of the disease gene within two overlapping BAC clones (< 360 kb)

Urofacial (Ochoa) syndrome is an autosomal recessive disease characterized by distorted facial expression and urinary abnormalities. Previously, we ma pped the UFS gene to chromosome 10q23-q24 and narrowed the interval to one YAC clone of 1410 kb. Here, we have constructed a BAC/PAC contig of the 1-M b region using STS content mapping with 42 BAC/ PAC-end sequences, 9 previo usly reported and 16 newly identified microsatellite markers, and 14 EST ma rkers. A total of 26 polymorphic microsatellite markers were genotyped for 31 UFS patients from Colombia and 2 patients from the United States. Haplot ype analyses suggest that the UFS gene is located within two overlapping BA C clones, a region of <360 kb of DNA sequence. We tested 42 EST markers pre viously mapped to the D10S1709-D10S603 interval against the BAC/PAC contig and identified 11 ESTs located in the 1-Mb region. Four of the 11 ESTs mapp ed to the 360-kb UFS critical region. Shotgun sequencing of the two BAC clo nes and BLASTN search of the EST databases revealed 3 other ESTs contained in the UFS critical region. These results will facilitate the cloning and i dentification of the UFS gene. (C) 1999 Academic Press.