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Single-cell methylation analysis of brain tissue prioritizes mutations that alter transcription. | LitMetric

AI Article Synopsis

  • Understanding how genetic variants affect behavior is a major scientific challenge.
  • In a study of eight mouse strains, researchers found that DNA methylation plays a critical role in how genes express themselves based on the density of CpG sequences in the genome.
  • The results suggest that candidate genetic variants can be better prioritized for research based on their CpG density, indicating that DNA methylation influences mutation occurrence in a non-random manner.*

Article Abstract

Relating genetic variants to behavior remains a fundamental challenge. To assess the utility of DNA methylation marks in discovering causative variants, we examined their relationship to genetic variation by generating single-nucleus methylomes from the hippocampus of eight inbred mouse strains. At CpG sequence densities under 40 CpG/Kb, cells compensate for loss of methylated sites by methylating additional sites to maintain methylation levels. At higher CpG sequence densities, the exact location of a methylated site becomes more important, suggesting that variants affecting methylation will have a greater effect when occurring in higher CpG densities than in lower. We found this to be true for a variant's effect on transcript abundance, indicating that candidate variants can be prioritized based on CpG sequence density. Our findings imply that DNA methylation influences the likelihood that mutations occur at specific sites in the genome, supporting the view that the distribution of mutations is not random.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10726494PMC
http://dx.doi.org/10.1016/j.xgen.2023.100454DOI Listing

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