Somatic mutation and genomic diversity in human brain in development, disease, and degeneration - Christopher Walsh

Event Details:

Thursday, February 25, 2021
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Time
12:00pm to 1:00pm PST
Location
Contacts
neuroscience@stanford.edu
Event Sponsor
Wu Tsai Neurosciences Institute
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Wu Tsai Neurosciences Institute Seminar Series Presents

Christopher Walsh, MD, PhD 

Bullard Professor of Pediatrics and Neurology, HHMI, Harvard University

Host: Daniel Pederick (Luo Lab)

 

Abstract

Although it had long been assumed that the genomes of all neurons are identical, recent work shows that every cell division causes mutations even during normal development, and that postmitotic neurons continue to accumulate mutations throughout life even in the absence of cell division.  Recent studies implicate clonal somatic mutations in focal epilepsy, autism spectrum disorders, and schizophrenia. Reading out these developmental mutations reveals a forensic cell lineage map that records each cell division that generates each person.
Sequencing the DNA genome from a single neuron reveals a universe of genomic diversity, with transposon insertion, copy number variants, and hundreds of point mutations distinguishing the genome of one neuron from another.  Surprisingly, neurons accumulate a dozen of more mutations per year in human brain, with thousands of such mutations present in old age.  SNV accumulate faster in rare genetic disorders, associated with precocious neurodegeneration and are likely to play a role in more common forms of degeneration as well.  Supported by the NIMH, NINDS, and HHMI.