High resolution genetic map of the adenomatous polyposis coli gene (APC) region

Familial adenomatous polyposis coli (APC) is a dominantly inherited colorectal cancer susceptibility disease caused by mutation in a gene called APC and located on chromosome 5q21. Presymptomatic diagnosis of this condition is recommended because it enables restriction of the efficient but demanding prevention program to those relatives that are genetically affected. The large size of the APC gene makes the direct search for the causal alteration difficult to implement in routine diagnostic laboratories. Because APC appears to be genetically homogeneous with alteration in a single locus causing the disease, cosegregation analysis may represent an alternative efficient method for presymptomatic diagnosis. However, the reliability of the risk estimation by linkage analysis in APC families is hampered by the lack of a short range genetic map of the APC locus. A combined approach including genotyping of 65 APC families, analysis of the CEPH database, and complementary typing of both APC and CEPH families has made it possible to derive the following genetic map: Centromere-[D5S82-D5S49]-0.02-D5S122-0.01-D5S136 -0.01-D5S135-0.02-[APC-D5S346-MCC]-0.04-[D5S81-D5S6 4]-Telomere. This order, which differs from previously proposed genetic maps, is fully compatible with recent physical mapping data. These data should contribute to increase the reliability of the presymptomatic test for APC.