Grant: Project Grant

Babies born with a genetic deletion (missing piece of DNA) on one of the pair of chromosomes 22 are known to be at high risk of having birth defects and, later on, learning difficulties and schizophrenia. Some are severely affected and some have better outcomes, even though they have the same deletion. The deletion can be found in up to 1 in 1000 pregnancies, and is usually a change that is new to the family. New commercially available tests can now screen for this genetic deletion in pregnancy. Families, healthcare providers, and researchers want to anticipate and ultimately prevent the most disabling outcomes. There is evidence that additional changes elsewhere in a person's DNA are important to specific expression and outcomes of the deletion. By studying 100 Canadian adults who have this deletion on chromosome 22 and their 200 parents who do not have this deletion we will first determine how the parents' traits, like intellectual level, may modify outcomes. Then we will use the latest technology, whole genome sequencing, to sequence the entire genome (DNA) of these 300 people. This will enable us to identify and interpret other genetic changes, both new and inherited, that make it more (or less) likely for individuals with the deletion to develop specific features that affect lifelong outcome. To start, we will compare those with and without schizophrenia. Some new genetic changes may cluster together in the genome. We will examine whether these clusters are associated with poor outcomes, and/or with the occurrence of the deletion event itself in the family. The results promise to help identify factors that shape important outcomes in individuals with this deletion, so that we can intervene early and help to prevent major disabilities. This study will also advance our understanding of common diseases like schizophrenia, and of the many genetic conditions that are similar to this specific genetic deletion.