HIGH-RESOLUTION MAPPING OF THE X-LINKED LYMPHOPROLIFERATIVE SYNDROME REGION BY FISH ON COMBED DNA

X-linked lymphoproliferative syndrome is an inherited immunodeficiency for which the responsible gene is currently unknown. Several megabase -sized deleted regions mapping to Xq25 have been identified in XLP pat ients, and more recently a 130-kb deletion has been reported (Lamartin e et al., 1996; Lanyi et al., 1996). To establish a physical map of th is deleted region and to identify the XLP gene, two cosmid contigs wer e established (Lamartine et al., 1996). However, the physical map of t his region is still uncompleted and controversial and three points rem ain unsolved: (1) the centromeric-telomeric orientation of the whole r egion, (2) the relative orientation of the two contigs, and (3) the si ze of the gap between the two contigs. To provide a definitive answer to these questions, high-resolution mapping by fluorescence in situ hy bridization on combed DNA and molecular approaches were combined to es tablish the physical map of the XLP region over 600 kb. Our results id entified a gap of 150 kb between the two contigs, established the rela tive orientation of one contig to the other, and determine the centrom eric-telomeric orientation of the whole region. Our results show that the order of the marker over this region is: cen...1D10T7-DF83-DXS982. ..tel.