Why Bigger Brains Get More Mutations | Christopher Walsh | 306
Shownotes
How genomics is used to study what makes a human brain, and how genetically damaged neurons get removed.
TOPICS DISCUSSED:
- Scale & Size: A human brain is about three times a chimpanzee brain by mass, but the larger change is extra association cortex and extra upper-layer circuits that talk mostly to other cortex.
- When Development Ends: Most cortical neurons are born before birth. Myelin and other glia keep forming into the twenties. Synapses keep changing after that.
- Broken Genomes Get Edited: Walsh describes forthcoming work in which ~25–30% of late-fetal cortical neurons carry genetic defects, falling to ~5% by birth, with smaller defects still being removed through adult life.
- Regulation vs. New Genes: Humans and mice both have ~20,000 genes. Most human-specific change is in when and where those genes turn on, not in inventing new proteins.
- Human Accelerated Regions: About half of HARs involve the brain. Rare mutations in them show up more often in kids with intellectual disability and autism.
- ASPM & Microcephaly: Loss of one conserved cell-division gene can shrink a human brain toward chimpanzee volume and shape. The same knockout barely shrinks a mouse.
- Heritability of Genetic Disorders: Autism is highly heritable in twin studies. A whole-genome test today still finds a specific cause in only about a quarter to a third of kids.
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