Genomic contributions to Mendelian disease

Genomic research has two quite distinct faces. On the one hand, it produces large, curated, reference data sets through numerous networks of investigators for community use—although this aspect has great and widespread utility, it does not inspire per se. On the other hand, it allows an unbiased genome-wide view that is exciting precisely because it habitually uncovers biology that we were hopelessly ignorant about. Consequently, I am sanguine that the search for Mendelian disease genes by exomic and genomic sequencing will produce more than a long and comprehensive list of genes and associated disease mutations. Importantly, we are likely to hear new and surprising biological stories.