A radiation hybrid map of 48 loci including the Clouston hidrotic ectodermal dysplasia locus in the pericentromeric region of chromosome 13q

To facilitate the identification of the gene responsible for Clouston hidro tic ectodermal dysplasia (HED), we used a chromosome 13-specific radiation hybrid panel to map 54 loci in the HED candidate region. The marker retenti on data were analyzed using RHMAP version 3. The 54 markers have an average retention frequency of 31.6% with decreasing retention as a function of di stance from the centromere. Two-point analysis identified three linkage gro ups with a threshold lod score of 4.00; one linkage group consisted of 49 l oci including the centromeric marker D13Z1 and the telomeric flanking marke r for the HED candidate region D13S143. Assuming a centromeric retention mo del, multipoint maximum likelihood analysis of these 49 loci except D13Z1 p rovided a 1000:1 framework map ordering 29 loci with 21 unique map position s and similar to 2000 times more likely than the next order. Loci that coul d not be ordered with this level of support were positioned within a range of adjacent intervals. This map spans 347 cR(9000), has an average resoluti on of 17.3 cR(9000), and includes 3 genes (TUBA2, GJ beta 2, and FGF-9), 18 ESTs, 19 polymorphic loci, and 8 single-copy DNA segments. Comparison of o ur RH map to a YAC contig showed an inconsistency in order involving a reve rsed interval of 6 loci. Fiber-FISH and FISH on interphase nuclei analyses with PACs isolated from this region supported our order. We also describe t he isolation of 8 new chromosome 13q polymorphic (CA), markers that have an average PIC value of 0.67. These data and mapping reagents will facilitate the isolation of disease genes from this region. (C) 1999 Academic Press.