Aging and neurodegeneration are associated with increased mutations in single human neurons

It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant…

• HH
  Howard Hughes Medical Institute
• PG
  Paul G. Allen Family Foundation
• MC
  Manton Center for Orphan Disease Research, Boston Children's Hospital
• LC
  Ludwig Center at Harvard
• NI
  National Institute on Aging

  Award: K99 AG054749 01
• NI
  National Institute of Mental Health

  Awards: U01 MH106883, U01MH106883, F30 MH102909, P50MH106933
• NH
  National Human Genome Research Institute

  Award: T32HG002295
• NI
  National Institute of General Medical Sciences

  Award: T32GM007753
• NI
  National Institute of Neurological Disorders and Stroke

  Awards: R01 NS079277, R01 NS032457
• NC
  National Center for Research Resources

  Award: 1S10RR028832-01