Principal Investigator: Dr Santhosh Girirajan
Pennsylvania State University, University Park, Pennsylvania, USATags: 45023, Autism, Complex Traits, copy-number variants, genetic interactions, Machine Learning, neurodevelopment
Rare pathogenic copy-number variants (CNVs) are often characterized by variable expressivity of neuropsychiatric features among carriers of the same variant. This suggests a role for complex genetic interactions among genes both within the CNV region and with variants in the genetic background towards these clinical features. We propose to use the UK BioBank genomic and clinical datasets to understand the genetic complexity of neurodevelopmental features. We will first identify pathogenic CNVs among individuals with specific neurodevelopmental disorders, such as autism, intellectual disability and schizophrenia, as well as healthy control individuals within the cohort. Next, we will use machine-learning methods to correlate CNVs with phenotypes, and look for associations between genes affected by CNVs with individual neuropsychiatric phenotypes. Finally, we will identify potential interactions between genes within CNV regions associated with neurodevelopmental phenotypes. We hope to identify novel variants, interactions and biological pathways that modulate the neurodevelopmental phenotypes of individual genes within CNV regions.
The availability of both microarray and exome sequencing data for individuals in the UK BioBank will allow us to extend our analysis of associations between genes and specific neurodevelopmental phenotypes to include genes disrupted by both CNVs and SNVs. We will also be able to identify interactions between genes within CNV regions and variants in the genetic background to better understand the pathogenicity of variably expressive CNVs.
Last updated Aug 15, 2019