HIGH-RESOLUTION GENETIC-MAP OF THE ADENOMATOUS POLYPOSIS-COLI GENE (APC) REGION

Familial adenomatous polyposis coli (APC) is a dominantly inherited co lorectal cancer susceptibility disease caused by mutation in a gene ca lled APC and located on chromosome 5q21. Presymptomatic diagnosis of t his condition is recommended because it enables restriction of the eff icient but demanding prevention program to those relatives that are ge netically affected, The large size of the APC gene makes the direct se arch for the causal alteration difficult to implement in routine diagn ostic laboratories. Because APC appears to be genetically homogeneous with alteration in a single locus causing the disease, cosegregation a nalysis may represent an alternative efficient method for presymptomat ic diagnosis, However, the reliability of the risk estimation by linka ge analysis in APC families is hampered by the lack of a short range g enetic map of the APC locus, A combined approach including genotyping of 65 APC families, analysis of the CEPH database, and complementary t yping of both APC and CEPH families has made it possible to derive the following genetic map: 0.02-[APC-D5S346-MCC]-0.04-[D5S81-D5S64]-Telom ere. This order, which differs from previously proposed genetic maps, is fully compatible with recent physical mapping data, These data shou ld contribute to increase the reliability of the presymptomatic test f or APC. (C) 1995 Wiley-Liss, Inc.