HIGH-DENSITY PHYSICAL MAPPING OF A 3-MB REGION IN XP22.3 AND REFINED LOCALIZATION OF THE GENE FOR X-LINKED RECESSIVE CHONDRODYSPLASIA PUNCTATA (CDPX1)

The study of patients with chromosomal rearrangements has led to the m apping of the gene responsible for X-linked recessive chondrodysplasia punctata (CDPX1; MIM 302950) to the distal part of the Xp22.3 region, between the loci PABX and DXS31. To refine this mapping, a yeast arti ficial chromosome (YAC) contig map spanning this region has been const ructed. Together with the YAC contig of the pseudoautosomal region tha t we previously established, this map covers the terminal 6 Mb of Xp, with an average density of 1 probe every 100 kb. Newly isolated probes that detect segmental X-Y homologies on Yp and Yq suggest multiple co mplex rearrangements of the ancestral pseudoautosomal region during ev olution. Compilation of the data obtained from the study of individual s carrying various Xp22.3 deletions led us to conclude that the CDPX d isease displays incomplete penetrance and, consequently, to refine the localization of CDPX1 to a 600-kb interval immediately adjacent to th e pseudoautosomal boundary. This interval, in which 12 probes are orde red, provides the starting point for the isolation of CDPX1. (C) 1995 Academic Press, Inc.