Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders

Area of Science:

• Genetics
• Environmental Health
• Neuroscience

Background:

• * De novo mutations are significant in sporadic psychiatric and developmental disorders.
• * The role of environmental carcinogens in driving mutations for neurodevelopmental disorders (NDDs) is understudied.

Purpose of the Study:

• * To investigate the environmental mutation vulnerability of gene sets associated with diseases.
• * To explore how sequence characteristics influence mutation vulnerability in disease-related genes.

Main Methods:

• * Analyzed whole genome sequencing data from human cell lines exposed to carcinogens and lung cancers from polluted regions.
• * Compared mutation rates in disease-associated genes versus control genes using exact binomial tests.
• * Modeled sequence length, gene expression, and GC content effects on mutation rates using Quasi-Poisson regressions.

Main Results:

• * Radiation and polycyclic aromatic hydrocarbons disproportionately mutated genes linked to autism spectrum disorder, schizophrenia, and ADHD.
• * Genes for other diseases like ALS and Alzheimer's showed no significant mutation bias.
• * Sequence length, gene expression, and GC content influenced mutation rates differently for entire genes versus coding sequences.

Conclusions:

• * Environmental mutagens can disproportionately affect genes relevant to NDDs.
• * Findings support a role for environment-induced germline and somatic mutations in NDD etiology.