28 March 2014
US researchers have outlined progress in a Medical Exome Project at the annual meeting of the American College of Medical Genetics and Genomics (ACMG).
The project aims to act as a stepping stone in the move from using gene panels for clinical investigation (allowing testing of a limited number of genes, with correspondingly limited sensitivity) towards clinical whole genome sequencing (WGS) or whole exome sequencing (WES). Falling costs and speeds are increasingly making WGS an WES feasible for clinical investigation, and offer scope for greatly increased sensitivity – but at the same time, identify variants of unknown clinical significance and in genes unrelated to the clinical question.
The Medical Exome Project is developing an intermediate approach of enhanced medical exome targeting. This involves two elements, the first being production of a free, curated database of clinically relevant genes (the ‘medical exome’); clinically relevant genes are those previously implicated in disease, disease risk or drug responses. Talking at the ACMG meeting, Avni Santani of the Children’s Hospital of Philadelphia reported that they are developing a curation framework to facilitate the addition of new genes as they are identified.
The second element of the project is devising ways to enhance the performance of targeted DNA sequencing of these genomic regions, and a new exome capture kit to provide more accurate coverage has been developed.
The Medical Exome Project is said to be intended to complement other efforts to create databases of curated clinical genome and exome information, although whether it will ever prove possible to amalgamate the different national and international initiatives of this kind into a single massive resource for everyday clinical use remains to be seen; it would certainly be a mammoth undertaking.