Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements.

ABSTRACT: Accurate somatic mutation detection from single-cell DNA sequencing is challenging due to amplification-related artifacts. To reduce this artifact burden, an improved amplification technique, primary template-directed amplification (PTA), was recently introduced. We analyzed whole-genome sequencing data from 52 PTA-amplified single neurons using SCAN2, a new genotyper we developed to leverage mutation signatures and allele balance in identifying somatic single-nucleotide variants (SNVs) and small insertions and deletions (indels) in PTA data. Our analysis confirms an increase in nonclonal somatic mutation in single neurons with age, but revises the estimated rate of this accumulation to 16 SNVs per year. We also identify artifacts in other amplification methods. Most importantly, we show t

SUBMITTER: Luquette LJ 

PROVIDER: S-EPMC9833626 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature