Rare genetic disorders, while individually rare, are collectively common. They represent some of the most severe disorders affecting patients worldwide with significant morbidity and mortality. Over the last decade, advances in genomic methods have significantly uplifted diagnostic rates for patients and facilitated novel and targeted therapies. However, many patients with rare genetic disorders remain undiagnosed. While there are many reasons for diagnosis rates remaining incomplete, a major challenge is that many of the genes underlying mendelian phenotypes have not yet been linked to disease. I will describe existing strategies to identify novel Mendelian genes, including efforts through the GREGoR Consortium (Genomics Research to Elucidate the Genetics of Rare diseases). These will include the importance of data sharing for gene and variant matching, the utilisation of large-scale genomic sequencing projects, multiomic technologies (RNA-seq, long-read sequencing, etc.), and constraint-based reference population methods. Wider adoption of these methods will increase diagnosis rates, facilitating the delivery of improved medical care.
Anne O’Donnell-Luria (Sun,) studied this question.