International cooperation to enable the diagnosis of all rare genetic diseases
An article published by Boycott, Rath et al., in The American Journal of Human Genetics details the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. According to the authors, since the introduction of Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) in 2010, the pace of the discovery of genes underlying rare genetic diseases per year has increased, and the roportion of discoveries made by WES or WGS or by conventional approaches has steadily increased. Since 2013, WES and WGS have discovered nearly three times as many genes as conventional approaches, but the rate of discovery appears to be declining. Additionally, since 2010, the proportion of discoveries that are new disease-gene relations each year (known genes associated with a new disease) has steadily increased, but since 2013, the rate of discovery of both novel genes and new disease-gene relations appears to be declining. The authors then describe the critical role of the International Rare Diseases Research Consortium (IRDiRC), which was established in 2011 to bring together researchers and organisations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. According to the authors a non-trivial number of well-known rare diseases for which, despite multiple groups’ efforts to use WES and, in some cases, WGS, the causal genetic mechanism remains elusive. The reasons that such discovery efforts fail are myriad and most likely include both technical limitations and complex biology. The authors also provide reasons why IRDiRC is poised to achieve its goal of diagnosing all rare genetic diseases and the critical steps ahead to reach this goal.
