Transcription map of Xq27: Candidates for several X-linked diseases

Human Xq27 contains candidate regions for several disorders, yet is predict ed to be a gene-poor cytogenetic band. We have developed a transcription ma p for the entire cytogenetic band to facilitate the identification of the r elatively small number of expected candidate genes. Two approaches were tak en to identify genes: (1) a group of 64 unique STSs that were generated dur ing the physical mapping of the region were used in RT-PCR with RNA from hu man adult and fetal brain and (2) ESTs that have been broadly mapped to thi s region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four disti nct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for s everal rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and Borjeson-Forssm an-Lehman syndrome). Two transcriptionally active regions were identified i n the center of Xq27 and include candidate regions for X-linked mental reta rdation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth regi on of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE ) genes. The analysis thus suggests clustered transcription in Xq27 and pro vides candidates for several heritable disorders for which the causative ge nes have not yet been found. (C) 1999 Academic Press.