The BSMN will generate comprehensive maps of somatic genomic variation in neurotypical and diseased human brains, including a prioritized call set of confirmed somatic variants (Box 1) that may contribute to neuropsychiatric disease and epilepsy. Functional validation experiments will be performed using CRISPR/Cas9-mediated genome engineering, hiPSC-based neurogenesis, and mosaic mouse models generated by in utero electroporation (Fig. 3). The BSMN is initially determining concordance among disparate sequencing and bioinformatic approaches by performing a “common experiment” in which pulverized tissue from one neurotypical individual in the Lieber brain repository has been distributed to all of the working groups for independent assessment of mosaicism.
