The case studies illustrate how all this works in practice. Analysis of non-synonymous SNPs in the selectins leads to the finding of several that appear to be deleterious to protein function, but which do not directly lead to a disease phenotype. Inspection of homologs in the KnowledgeNet graphical interface suggests a role for functional redundancy in conferring network level robustness, and consulting mouse knockout and expression profile data supports that conclusion. The result also strongly suggests an epistatic relationship between the deleterious SNPs in selectin E and selectin P: An individual homozygous in either one will likely not display clinical symptoms, but an individual homozygous in both will probably have a significantly compromised inflammatory response. In the hypertension example, a list of possible candidate genes is generated. The KnowledgeNet interface allows a user to browse the relationships between those genes, clustering the main pathways, and providing access to analysis of the relevant non-synonymous SNPs. As is often the case, the roles of the some of the genes in disease susceptibility are complicated, and the available information is some times contradictory.
