REFINED MAPPING AND YAC CONTIG CONSTRUCTION OF THE X-LINKED CLEFT-PALATE AND ANKYLOGLOSSIA LOCUS (CPX) INCLUDING THE PROXIMAL X-Y HOMOLOGY BREAKPOINT WITHIN XQ21.3

The gene for X-linked cleft palate (CPX) has previously been mapped in an Icelandic kindred between the unordered proximal markers DXS1002/D XS349/DXS95 and the distal marker DXYS1X, which maps to the proximal e nd of the X-Y homology region in Xq21.3. Using six sequence-tagged sit es (STSs) within the region, a total of 91 yeast artificial chromosome (YAC) clones were isolated and overlapped in a single contig that spa ns approximately 3.1 Mb between DXS1002 and DXYS1X. The order of micro satellite and STS markers in this was established as -DXS1168-DSX349-D XS95-DXS364-DXS1196-DXS262-DXS110 - DXS1066 - (DXS1169, DXS1222) - DXS 472-DXS1217-DXYS1X. A long-range restriction map of this region was cr eated using eight nonchimeric, overlapping YAC clones. Analysis of new ly positioned polymorphic markers in recombinant individuals from the Icelandic family has enabled us to identify DXS1196 and DXS1217 as the flanking markers for CPX. The maximum physical distance containing th e CPX gene has been estimated to be 2.0 Mb, which is spanned by a mini mum set of five nonchimeric YAC clones. In addition, YAC end clone and STS analyses have pinpointed the location of the proximal boundary of the X-Y homology region within the map. (C) 1996 Academic Press, Inc.