Random allelic expression in the adult human body.
CP: Molecular biology
aging
allele-specific expression
cancer
dementia
gene expression
gene regulation
human genome
random monoallelic expression
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
31 01 2023
31 01 2023
Historique:
received:
14
04
2022
revised:
17
10
2022
accepted:
15
12
2022
pubmed:
15
1
2023
medline:
7
2
2023
entrez:
14
1
2023
Statut:
ppublish
Résumé
Genes are typically assumed to express both parental alleles similarly, yet cell lines show random allelic expression (RAE) for many autosomal genes that could shape genetic effects. Thus, understanding RAE in human tissues could improve our understanding of phenotypic variation. Here, we develop a methodology to perform genome-wide profiling of RAE and biallelic expression in GTEx datasets for 832 people and 54 tissues. We report 2,762 autosomal genes with some RAE properties similar to randomly inactivated X-linked genes. We found that RAE is associated with rapidly evolving regions in the human genome, adaptive signaling processes, and genes linked to age-related diseases such as neurodegeneration and cancer. We define putative mechanistic subtypes of RAE distinguished by gene overlaps on sense and antisense DNA strands, aggregation in clusters near telomeres, and increased regulatory complexity and inputs compared with biallelic genes. We provide foundations to study RAE in human phenotypes, evolution, and disease.
Identifiants
pubmed: 36640362
pii: S2211-1247(22)01846-0
doi: 10.1016/j.celrep.2022.111945
pmc: PMC10484211
mid: NIHMS1870509
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111945Subventions
Organisme : NIMH NIH HHS
ID : R21 MH118570
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH120468
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG012252
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109577
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG064013
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The University of Utah has filed a patent related to this work. C.G. is a co-founder of and has equity in Storyline Health Inc., which uses artificial intelligence to build scalable research and clinical tools for precision medicine.
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