The application of genetics to inherited bleeding disorders

Summary.  Most bleeding disorders encountered in clinical practice will be diagnosed, at least initially, by phenotypic assays. However, since the characterization of the genes that encode coagulation factors in the 1980s, significant progress has been made in translating this knowledge for diagnostic and therapeutic purposes. For the haemophilias, in particular, molecular genetic testing to determine carrier status, prenatal diagnosis and prediction of the likelihood of inhibitor development has now become an established component of comprehensive clinical management. For von Willebrand’s disease (VWD), significant recent advances have allowed for the establishment of genotype–phenotype correlations that have improved our understanding of the disease. The availability of high density single nucleotide polymorphism (SNP) maps will allow investigators to probe the genetic basis of the general symptoms of bleeding and bruising using a comprehensive genome-wide approach. This article will review the state-of-the-art for molecular diagnostics for both haemophilia and VWD and will end with a discussion of plans for an international genome-wide association study (GWAS) designed to improve our understanding of blood coagulation.