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Title: Single-cell damagenome profiling unveils vulnerable genes and functional pathways in human genome toward DNA damage
We report a novel single-cell whole-genome amplification method (LCS-WGA) that can efficiently capture spontaneous DNA damage existing in single cells. We refer to these damage-associated single-nucleotide variants as “damSNVs,” and the whole-genome distribution of damSNVs as the damagenome. We observed that in single human neurons, the damagenome distribution was significantly correlated with three-dimensional genome structures. This nonuniform distribution indicates different degrees of DNA damage effects on different genes. Next, we identified the functionals that were significantly enriched in the high-damage genes. Similar functionals were also enriched in the differentially expressed genes (DEGs) detected by single-cell transcriptome of both Alzheimer’s disease (AD) and autism spectrum disorder (ASD). This result can be explained by the significant enrichment of high-damage genes in the DEGs of neurons for both AD and ASD. The discovery of high-damage genes sheds new lights on the important roles of DNA damage in human diseases and disorders.  more » « less
Award ID(s):
2021795
PAR ID:
10332307
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Science Advances
Volume:
7
Issue:
27
ISSN:
2375-2548
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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