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Genetic regulation ...
Genetic regulation of gene expression and splicing during a 10-year period of human aging
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- Balliu, Brunilda (author)
- Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA
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- Durrant, Matthew (author)
- Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA
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- de Goede, Olivia (author)
- Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA
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- Abell, Nathan (author)
- Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA
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- Li, Xin (author)
- Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA
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- Liu, Boxiang (author)
- Stanford Univ, Dept Biol, Sch Med, Stanford, CA USA
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- Gloudemans, Michael J. (author)
- Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA
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- Cook, Naomi L. (author)
- Uppsala universitet,Molekylär epidemiologi,Uppsala Univ, Dept Med Sci, Uppsala, Sweden
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- Smith, Kevin S. (author)
- Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA
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- Knowles, David A. (author)
- New York Genome Ctr, New York, NY USA
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- Pala, Mauro (author)
- Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy
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- Cucca, Francesco (author)
- Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy
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- Schlessinger, David (author)
- NIA, Lab Genet, Bethesda, MD USA
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- Jaiswal, Siddhartha (author)
- Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA
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- Sabatti, Chiara (author)
- Stanford Univ, Dept Biomed Data Sci, Sch Med, Stanford, CA USA
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- Lind, Lars (author)
- Uppsala universitet,Klinisk epidemiologi
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- Ingelsson, Erik (author)
- Stanford Univ, Sch Med, Div Cardiovasc Med, Dep Med, Stanford, CA USA; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA USA
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- Montgomery, Stephen B. (author)
- Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA; Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA
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(creator_code:org_t)
- 2019-11-04
- 2019
- English.
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 20:1
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https://doi.org/10.1...
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https://doi.org/10.1...
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Abstract
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- Background: Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age.Results: We perform RNA sequencing in whole blood from the same individuals at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging at a population and individual level. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age. We identify 1291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories. Further, we observe a strong correlation of genetic effects on expression and splicing between the two ages, with a small subset of tested genes showing a reduction in genetic associations with expression and splicing in older age.Conclusions: These findings demonstrate that, although the transcriptome and its genetic regulation is mostly stable late in life, a small subset of genes is dynamic and is characterized by a reduction in genetic regulation, most likely due to increasing environmental variance with age.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Keyword
- Aging
- Longevity
- Gene expression
- Alternative splicing
- Gene regulation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Balliu, Brunilda
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Durrant, Matthew
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de Goede, Olivia
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Abell, Nathan
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Li, Xin
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Liu, Boxiang
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show more...
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Gloudemans, Mich ...
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Cook, Naomi L.
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Smith, Kevin S.
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Knowles, David A ...
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Pala, Mauro
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Cucca, Francesco
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Schlessinger, Da ...
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Jaiswal, Siddhar ...
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Sabatti, Chiara
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Lind, Lars
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Ingelsson, Erik
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Montgomery, Step ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
- Articles in the publication
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Genome Biology
- By the university
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Uppsala University