Several rare genetic diseases are linked to structural variations (SV) such as duplications and deletions. These SVs typically alter the gene dosage of the genes with which they overlap: gain of function in copy number gains and loss of function in copy number losses. Recently, we and others showed that SVs that target non-coding DNA can cause gene mis-expression and rare genetic diseases. The goal of this study is to see if SVs contribute to common traits in the UK biobank, such as bone, cardiovascular and ophthalmological diseases. Non-coding, rare, big variations (structural ones) have yet to be discovered as contributors to common diseases and traits. Is it possible that rare SVs in common diseases are missed due to technological limitations or a lack of interpretation tools? Can we discover new common disease mechanisms by studying rare mutations in non-coding DNA? Does the 3D chromatin rearrangement affect prevalent diseases and traits? These are the questions we hope to answer with this study proposal.
