Abstract

Genomic mosaicism is prevalent throughout human somatic tissues and is much more common than previously thought. Here, we describe step-by-step methods to isolate neuronal nuclei from human brain and identify megabase scale copy number variants (CNVs) in single nuclei. The approach detailed herein includes use of CellRaft technology for single nucleus isolation, the PicoPLEX approach to whole genome amplification and library preparation, and a pooled library purification protocol, termed Gel2Gel, which has been developed in our laboratory. These methods are focused toward neuroscience research, but are adaptable to many biomedical fields.