AN XP22.1-P22.2 YAC CONTIG ENCOMPASSING THE DISEASE LOCI FOR RS, KFSD, CLS, HYP AND RP15 - REFINED LOCALIZATION OF RS

To facilitate the positional cloning of the genes involved in retinosc hisis (RS), keratosis follicularis spinulosa decalvans (KFSD), Coffin- Lowry syndrome (CLS), X-linked hypophosphatemic rickets (XLH, locus na me HYP) and X-linked dominant cone-rod degeneration (locus name RP 15) , we have extended the molecular map of the Xp22 region. Screening of several YAC libraries allowed us to identify 156 YACs, 52 of which loc alize between markers DXS414 (P90) and DXS451 (kQST80H1). Analysis of their marker content facilitated the construction of a YAC contig from the region spanning (in this order): DXS414 - DXS987 - DXS207 - DXS10 53 - DXS197 - DXS43 - DXS1195 - DXS418 - DXS999 - PDHA1 - DXS7161 - DX S443 - DXS7592 - DXS1229 - DXS365 - DXS7101 - DXS7593 - DXS1052 - DXS2 74 - DXS989 - DXS451. The region between DXS414 and DXS451 covers abou t 4.5-5 Mb. Two additional markers (DXS7593 and DXS7592) were placed i n the region, thereby increasing the genetic resolution. Using the ded uced marker order, the analysis of key recombinants in families segreg ating RS allowed us to refine the critical region for RS to 0.6 Mb, be tween DXS418 and DXS7161.