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Genetic Variation

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Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model

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Published on: September 29, 2011

Genetic variation in healthy oldest-old.

Julius Halaschek-Wiener¹, Mahsa Amirabbasi-Beik, Nasim Monfared

¹Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

|August 15, 2009

Summary

Healthy aging involves genetic factors. Researchers studied 47 healthy individuals aged 85+ and identified 935 genetic variants, including novel ones, in aging-related genes.

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A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

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Area of Science:

Genetics
Gerontology
Molecular Biology

Background:

Healthy aging to 85+ years involves genetic and environmental factors.
Individuals may achieve longevity by lacking disease susceptibility or possessing resistance factors.
Exceptional longevity is a complex phenotype influenced by various biological pathways.

Purpose of the Study:

To characterize genetic variation in healthy individuals aged 85 years and older (the 'oldest-old').
To identify genetic factors contributing to healthy aging and disease resistance.
To analyze variations in candidate genes related to aging processes.

Main Methods:

DNA sequencing of 24 candidate healthy aging genes in 47 healthy oldest-old individuals.
Re-sequencing of exons, intron-exon boundaries, and conserved non-coding sequences.
Analysis of genes involved in dietary restriction, metabolism, autophagy, stem cell activation, tumor suppression, DNA methylation, progeria syndromes, and stress response.

Main Results:

Identified 935 genetic variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertions/deletions.
41% (385) of detected variants were novel, not previously recorded in dbSNP.
Comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old.

Conclusions:

This study provides a valuable resource of genetic variants, particularly novel polymorphisms, in healthy centenarians.
These variants can be used to test for genetic associations in disease susceptibility or resistance models.
An innovative tagSNP selection strategy combining re-sequencing and HapMap data is proposed.