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Approved research

Understanding the genetic complexity of neuropsychiatric features in copy-number variant disorders

Principal Investigator: Dr Santhosh Girirajan
Approved Research ID: 45023
Approval date: May 14th 2019

Lay summary

Rare copy-number variants (CNVs), which are large regions of DNA spanning multiple genes that are either duplicated or deleted in an individual, have been associated with several developmental disorders, including autism, schizophrenia, and intellectual disability. In many cases, individuals with the same CNV have very different clinical features. For example, only 40% of individuals with a deletion on chromosome 16p11.2 have autism, while intellectual disability, epilepsy and obesity are also observed in carriers of the deletion. Because of this, it is likely that multiple genes within each CNV region interact with each other and other genes with mutations outside of the CNV to produce the unique set of clinical features in each individual. In this study, we plan to use the UK BioBank data to explore complex interactions between genes that underlie the clinical features of CNVs. We will first identify individuals with developmental disorders in the UK BioBank cohort, and compare frequencies of CNVs between each group with a group of healthy individuals to identify any CNVs that have not been previously described. Next, we will develop new computational methods to uncover associations between genes within CNV regions and specific clinical features, such as an association between genes that function early in development and autism. We will finally map genes associated with clinical features to networks of gene interactions to see if they interact with each other and share a similar function. Our project, which will last for three years, will hopefully identify common functions of genes within CNV regions that are associated with the clinical features of CNV carriers. This will allow researchers to test whether drugs that affect the same functions can be used to treat the clinical features of CNV carriers. Further, if we identify any new CNVs in our study, individuals carrying those CNVs will be able to receive a genetic diagnosis and potential treatment options for their clinical features.