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Experimental Section / Short Communication

Burden of Common Complex Disease Variants in the Exomes of Two Healthy Centenarian Brothers

Tindale L.C.a, b · Zeng A.a, b · Bretherick K.L.b · Leach S.b · Thiessen N.b · Brooks-Wilson A.R.a, b

Author affiliations

aDepartment of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, B.C., and bCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, B.C., Canada

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Gerontology 2016;62:58-62

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Article / Publication Details

First-Page Preview
Abstract of Experimental Section / Short Communication

Received: January 19, 2015
Accepted: April 14, 2015
Published online: June 10, 2015
Issue release date: December 2015

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 1

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER

Abstract

Background: It is not understood whether long-term good health is promoted by the absence of disease risk variants, the presence of protective variants, or both. We characterized the exomes of two exceptionally healthy centenarian brothers aged 106 and 109 years who had never been diagnosed with cancer, cardiovascular disease, diabetes, Alzheimer's disease, or major pulmonary disease. Objective: The aim of this study was to gain insight into whether exceptional health and longevity are a result of carrying fewer disease-associated variants than typical individuals. Methods: We compared the number of disease-associated alleles, and the proportion of alleles predicted to be functionally damaging, between the centenarian brothers and published population data. Mitochondrial sequence reads were extracted from the exome data in order to analyze mitochondrial variants. Results: The brothers carry a similar number of common disease-associated variants and predicted damaging variants compared to reference groups. They did not carry any high-penetrance clinically actionable variants. They carry mitochondrial haplogroup T, and one brother has a single heteroplasmic variant. Conclusion: Although our small sample size does not allow for definitive conclusions, a healthy aging and longevity phenotype is not necessarily due to a decreased burden of common disease-associated variants. Instead, it may be rare ‘positive' variants that play a role in this desirable phenotype.

© 2015 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Experimental Section / Short Communication

Received: January 19, 2015
Accepted: April 14, 2015
Published online: June 10, 2015
Issue release date: December 2015

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 1

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


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