WGA can be used to analyze the genomes of single neurons (26). The spectrum of mutations identified from the genomes of single neurons can then be compared to germline variants in bulk tissue data derived from a non-neuronal control (e.g., brain dural fibroblasts or heart) to identify candidate somatic mutations (5). WGA approaches already are used in pre-implantation genetic screening of embryos (76, 77) and include (i) degenerate-oligonucleotide-primed PCR (DOP-PCR), (ii) multiple displacement amplification (MDA), and (iii) multiple annealing and looping-based amplification (MALBAC). Each method has its advantages and drawbacks. In general, DOP-PCR provides coverage evenly across the genome, which facilitates the detection of large CNVs and chromosomal aneuploidies. However, DOP-PCR has a higher read duplication rate, lower mapping rate, and lower recovery rate when compared with MDA and MALBAC (78) and is cost prohibitive for SNV, indel, and MEI detection. By comparison, MDA yields a high rate of artificial chimeric DNA molecules that can lead to false-positive calls in downstream analyses (79), whereas MALBAC exhibits reduced coverage of certain genomic regions (14, 16, 80), especially those rich in repetitive
