Rare diseases are arbitrarily defined as those that affect fewer than 200,000 individuals in the U.S. Per this definition, more than 7,000 rare diseases have been delineated, and in aggregate these affect more than 25 million people [Rare Diseases Act of 2002, Section 2, Findings]. The majority of these diseases are “genetic disorders” and many of them are thought to be monogenic. The bulk of genes underlying these rare monogenic diseases remain unknown. Lack of information about the genes and pathways that underlie rare monogenic diseases is a major gap in our scientific knowledge. Discovery of the genetic basis of a large collection of rare disorders that have, to date, been unyielding to analysis will substantially expand our understanding of biology of rare diseases, facilitate accurate diagnosis and improved management, and provide initiative for further investigation of novel therapeutics.
