Discovering the genes and genetic variants underlying human Mendelian disorders is of significant biomedical relevance. The knowledge of those variants, which are rare and highly penetrant, will facilitate rapid and accurate diagnosis of Mendelian disorders and might lead to new therapeutic approaches. This knowledge can also lead to insight about the common or more complex phenotypes that involve similar genes, pathways, and phenotypes. In the long run, a comprehensive collection of rare and highly penetrant variants would be a highly valuable resource for understanding basic human genetics and would identify entry points into fundamental developmental and physiological pathways.
While the genetic basis of more than 3000 Mendelian disorders has been determined so far, the genetic basis remains to be determined for a large number of confirmed or suspected Mendelian disorders. Recent advances in genome technology and computational methods have made it possible to identify the genetic basis of Mendelian disorders using genome-wide approaches in a more rapid and cost-effective way than linkage mapping and candidate gene approaches.
The Centers for Mendelian Genomics (CMG) are co-funded by NHGRI and the National Heart, Lung, and Blood Institute of National Institutes of Health (NHLBI). The CMG aim to make major contributions to the discovery of the genetic basis of most or all Mendelian disorders in two main ways. The first is to use genome-wide sequencing and other genomic approaches to discover the genetic basis underlying as many Mendelian traits as possible, spanning the various Mendelian inheritance patterns, during the funding period. The second is to accelerate the discovery by disseminating the obtained knowledge and effective approaches, reaching out to individual investigators, and coordinating with other rare disease programs worldwide.