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Whole-genome sequencing of the world's oldest people.

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.

SUBMITTER: Gierman HJ

PROVIDER: S-EPMC4229186 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Whole-genome sequencing of the world's oldest people.

Gierman Hinco J HJ Fortney Kristen K Roach Jared C JC Coles Natalie S NS Li Hong H Glusman Gustavo G Markov Glenn J GJ Smith Justin D JD Hood Leroy L Coles L Stephen LS Kim Stuart K SK

PloS one 20141112 11

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 m ...[more]

PMID: 25390934

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Whole-genome sequencing of the world's oldest people.

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Whole-genome sequencing of the world's oldest people.

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