Whole-genome sequencing of the world's oldest people

PLoS One. 2014 Nov 12;9(11):e112430. doi: 10.1371/journal.pone.0112430. eCollection 2014.

Abstract

Supercentenarians (110 years or older) are the world's oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Aging / genetics*
  • Desmocollins / genetics
  • Female
  • Genome, Human*
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics
  • Humans
  • Longevity / genetics*
  • Male
  • Mutation
  • Sequence Analysis, DNA

Substances

  • DSC2 protein, human
  • Desmocollins
  • Homeodomain Proteins
  • TSHZ3 protein, human