LOCATION ON THE HUMAN GENETIC-LINKAGE MAP OF 26 GENES INVOLVED IN BLOOD-COAGULATION

Several human genetic linkage maps have been constructed as part of th e Human Genome Project. These maps show the positional order of closel y linked, highly informative AC-repeat polymorphisms on each human chr omosome, and are extremely useful in genetic linkage analysis of inher itable diseases. For a candidate gene approach the cur rent linkage ma ps are less useful, since they consist mainly of anonymous markers rat her than of specific genes. This situation also applies for inheritabl e disorders of blood coagulation. Numerous genes are involved in the b lood coagulation cascade and its regulation, and can be considered as candidate genes for unexplained haemophilia and thrombophilia. We have selected 29 candidate genes that seem to be the ones mast likely to b e involved in thrombophilia. For 19 genes genotype data were already p resent in the CEPH database (version 7.0). We typed 7 additional genes in the CEPH reference families, i.e. the factor V, factor XII, protei n C, protein S, prothrombin, thrombomodulin, and heparin cofactor II g ene, The genotype data were used to integrate these 26 genes in the cu rrent genetic linkage map, and to identify closely linked AC-repeat po lymorphisms, This information will benefit the investigation of inheri table disorders of blood coagulation, especially thrombophilia.