Somatic mutation in single human brain cells

Posted by & filed under Exome sequencing, Part 03: GENERAL THEMES, Part 28: NEUROGENETICS.

Neurons live for decades in a postmitotic state and their genomes are susceptible to DNA damage. Using genome sequencing for individual human brain cells (postmortem), Lodato et al. have searched for somatic single-nucleotide variants (SNVs) in the human brain. After sequencing 36 neurons from the cerebral cortex of three normal individuals, they demonstrated that the average human neuron carries 1700 mutations.

Most of these mutations were unique to single neurons, rather than present in all cells, suggesting that most brain mutations arise after the brain has fully formed. Also, unlike germline and cancer SNVs, which are often caused by errors in DNA replication, in this study mutations were enriched in genes involved in neural function and development and are thought to have happened during gene transcription.

Somatic mutation in single human neurons tracks developmental and transcriptional history. Lodato et al. Science. 2015 Oct 2;350(6256):94-8.

Posted by Yannis Trakadis, MD

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