Genome Analysis for Disease Variant Identification
Unravelling human developmental disease
Developmental disorders are characterized by congenital malformations, abnormalities in growth and/or in neurological development. Although developmental disorders are individually rare, collectively they affect 2% of the population, representing a major health and economic burden for society. Because an important proportion of developmental disorders are caused by genetic mutations, affected individuals often undergo extensive testing involving microarrays or Next Generation Sequencing. For affected families, a clear genetic diagnosis is key to understanding the cause of their disease, receiving better medical treatment and making informed health-related decisions. However, despite embarking on diagnostic odysseys involving microarrays, whole exome sequencing or even whole genome sequencing, over 50% of individuals with developmental disorders remain without genetic diagnosis. This diagnostic gap exposes the limitations of current technologies to detect and interpret disease-causing mutations. For instance, whole genome sequencing can detect mutations throughout the genome but pinpointing a disease-causing mutation among hundreds of thousands of benign variants remains a daunting task. Thus, accurate identification of disease-causing mutations, especially in non-coding regions of the genome, currently represents a major challenge in human genetics.
To address this challenge, we are applying state-of-the-art functional genomics technologies to identify pathogenic mutations underlying human developmental disease and dissect the molecular mechanism through which these alterations disrupt human development. Our research aims to better understand the genetic causes and mechanisms of currently unsolved developmental disorders. Ultimately, our goal is to translate results from basic research carried out at the lab bench into the clinic by improving current methods of genetic diagnosis and setting a base on which to provide better medical treatment and accurate genetic counselling to individuals affected by developmental disorders.