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Related Experiment Video

Updated: Jan 19, 2026

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
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Allele-Specific Transcript Abundance: A Pilot Study in Healthy Centenarians.

Lauren C Tindale1,2, Nina Thiessen1, Stephen Leach1

  • 1Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|September 11, 2019
PubMed
Summary

Healthy aging and longevity may involve allele-specific abundance (ASA), where gene expression levels differ between individuals. This pilot study found no significant differences in ASA patterns between centenarians and controls.

Keywords:
GeneticsHuman agingLongevityTranscriptomics

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Area of Science:

  • Genetics
  • Molecular Biology
  • Gerontology

Background:

  • The genetic underpinnings of healthy aging and longevity are not fully understood.
  • A hypothesis suggests long-lived individuals may mitigate common disease risk variants by expressing them at lower levels.
  • Allele-specific abundance (ASA) refers to differential transcript levels between haplotypes in diploid individuals.

Purpose of the Study:

  • To investigate allele-specific abundance (ASA) in healthy centenarians compared to mid-life controls.
  • To explore the role of ASA in the genetic basis of longevity.
  • To identify potential differences in gene expression patterns related to aging and disease risk.

Main Methods:

  • Transcriptome sequencing of four healthy centenarians and four mid-life controls.
  • Utilizing CIBERSORT to estimate blood cell fractions (neutrophils, CD8+ T cells, NK cells, monocytes).
  • Analyzing ASA variants, their distribution by predicted effect, and their representation in immune pathways.

Main Results:

  • ASA variants were more prevalent in noncoding than coding regions.
  • No overall bias in expression toward major or minor alleles was observed between centenarians and controls.
  • Immune pathways were highly represented in genes exhibiting ASA, with evidence in disease-associated genes and transcription factors, but no significant inter-group differences were found in this pilot study.

Conclusions:

  • This pilot study did not reveal significant differences in allele-specific abundance patterns between centenarians and controls.
  • While ASA was observed in immune-related genes and disease-associated factors, its role in exceptional longevity requires further investigation.
  • Future research with larger cohorts is needed to elucidate the genetic mechanisms of healthy aging and longevity.