Allele-Specific Transcript Abundance: A Pilot Study in Healthy Centenarians

Abstract The genetic basis of healthy aging and longevity remains largely unexplained. One hypothesis as to why long-lived individuals do not appear to have a lower number of common-complex disease variants, is that despite carrying risk variants, they express disease-linked alleles at a lower level...

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Bibliographic Details
Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2020-05, Vol.75 (6), p.1068-1072
Main Authors: Tindale, Lauren C, Thiessen, Nina, Leach, Stephen, Brooks-Wilson, Angela R
Format: Article
Language:English
Subjects:
Aged, 80 and over
Aging
Alleles
CD8 antigen
Centenarians
Diploids
Diploidy
Female
Gene expression
Gene Expression Profiling
Genes - genetics
Genetic Predisposition to Disease - genetics
Genetic Variation - genetics
Geriatrics
Haplotypes
Haplotypes - genetics
Healthy Aging - genetics
Humans
Leukocytes (neutrophilic)
Lymphocytes T
Male
Monocytes
Neutrophils
Oldest old people
Pilot Projects
Ribonucleic acid
RNA
THE JOURNAL OF GERONTOLOGY: Biological Sciences
Transcription factors
Transcriptome - genetics
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Summary:Abstract The genetic basis of healthy aging and longevity remains largely unexplained. One hypothesis as to why long-lived individuals do not appear to have a lower number of common-complex disease variants, is that despite carrying risk variants, they express disease-linked alleles at a lower level than the wild-type alleles. Allele-specific abundance (ASA) is the different transcript abundance of the two haplotypes of a diploid individual. We sequenced the transcriptomes of four healthy centenarians and four mid-life controls. CIBERSORT was used to estimate blood cell fractions: neutrophils were the most abundant source of RNA, followed by CD8+ T cells, resting NK cells, and monocytes. ASA variants were more common in noncoding than coding regions. Centenarians and controls had a comparable distribution of ASA variants by predicted effect, and we did not observe an overall bias in expression toward major or minor alleles. Immune pathways were most highly represented among the gene set that showed ASA. Although we found evidence of ASA in disease-associated genes and transcription factors, we did not observe any differences in the pattern of expression between centenarians and controls in this small pilot study.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/glz188