The goal of our parent grant, U01MH106891, ?Somatic Mosaicism in Schizophrenia and Control Brains? is to determine the extent to which somatic genomic variation contributes to schizophrenia. Mosaicism is the occurrence of two (or more) genomes in an individual who is derived from a single zygote. Members of the NIMH-supported Brain Somatic Mosiacism Network (BSMN) are characterizing mosaic variation in other neuropsychiatric disorders with a common goal of assessing the role of somatic mosaic variation across diseases including bipolar disorder, schizophrenia, autism spectrum disorder, and Tourette syndrome. We propose three capstone projects to map the full spectrum of somatic variation in human brain and characterize the contributions of mosaic variants to neuropsychiatric disease risk. These capstones can advance the mission of the BSMN, to both achieve greater power of discovery of somatic mutations by combining and harmonizing deep coverage whole genome sequencing data that have been generated across nodes, as well as placing the variants identified through the study of brain somatic mosaicism (BSM) in the context of neurodevelopment and disease. To integrate this multi-dimensional data from the BSMN, as well as other consortia, administrative supplements are requested to continue, in the final two years of the award, three capstone projects, as well as to contribute to the Data Coordinating Center (DCC) and data analytic core (DAC). We expect these Capstone Projects to increase the profile of the BSMN by creating an unprecedented data resource of somatic mosaicism variants across development and diseases widely available to the scientific community. The enhanced power provided by the combined analyses of the BSMN will provide foundational knowledge that will guide future work, and lead to new insight into brain somatic mosaicism.
The specific aims of this site are: SA1, for Capstone 1, Sage Bionetworks will be responsible the development of a BSMN website that will feature the consortium goals and members, provide an inventory of analytical tools and descriptions of best practices, and link to data and resources. SA2, for Capstone 3, Mount Sinai will participate in the analyses of RNA-seq data and paired DNA sequence data for the primary identification of somatic mosaicism.
As part of the Brain Somatic Mosaicism Network (BSMN) we will participate in cross-disorder analyses as well as creating (Sage's role) web interfaces for dissemination of knowledge and methodology from across the BSMN. 1
| Rodin, Rachel E; Walsh, Christopher A (2018) Somatic Mutation in Pediatric Neurological Diseases. Pediatr Neurol 87:20-22 |
| Dou, Yanmei; Gold, Heather D; Luquette, Lovelace J et al. (2018) Detecting Somatic Mutations in Normal Cells. Trends Genet 34:545-557 |
| McConnell, Michael J; Moran, John V; Abyzov, Alexej et al. (2017) Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science 356: |
