A 1.8-MB YAC CONTIG IN XP11.23 - IDENTIFICATION OF CPG ISLANDS AND PHYSICAL MAPPING OF CA REPEATS IN A REGION OF HIGH GENE DENSITY

The genes ARAF1, SYN1, TIMP, and PFC are clustered within 70 kb of one another, and, as reported in the accompanying paper (J. Knight et al. , 1994, Genomics 21: 180-187), at least four more genes map within 400 kb: a cluster of Kruppel-type zinc finger genes (including ZNF21, ZNF 41, and ZNF81) and ELK-1, a member of the ets oncogene superfamily. Th is gene-rich region is of particular interest because of the large num ber of disease genes mapping to Xp11.23: at least three eye diseases ( retinitis pigmentosa type 2, congenital stationary night blindness CSN B1, and Aland Island eye disease), Wiskott-Aldrich syndrome, X-linked nephrolithiasis and a translocation breakpoint associated with synovia l sarcoma. We have constructed a 1.8-Mb YAC contig in this region, con firming the link between TIMP and OATL1 reported by Knight et al. (199 4) and extending the map in the distal direction. To investigate the l ikelihood that more genes are located within this region, we have carr ied out detailed mapping of rare-cutter restriction sites in these YAC s and identified seven CpG islands. At least six of these islands are located over 50 kb from any known gene locations, suggesting that the region contains at least this many as yet unidentified genes. We have also mapped the physical locations of six highly polymorphic CA repeat s within the contig, thus integrating the physical, genetic, and trans criptional maps of the region and facilitating the mapping and identif ication of disease genes. Together with the report by Knight et al. (1 994), these data indicate the following order of loci: er-DXS1264-DXS1 055-DXS1003-DXS1146-DXS1266-(ZNF41, ARAF1)-SYN1 CA repeat-SYN1 (3' end )-TIMP-SYN1 (5' end)-PFC CA repeat-PFC(DXS426, ELK1)-(DXS1265, ZNF81)- ZNF21-DXS1267-OATL1-Xcen. (C) 1994 Academic Press, Inc.