Variant to Gene Mapping to Discover New Targets for Immune Tolerance.

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  • Author(s): Mehra P;Mehra P; Wells AD; Wells AD; Wells AD
  • Source:
    Frontiers in immunology [Front Immunol] 2021 Apr 15; Vol. 12, pp. 633219. Date of Electronic Publication: 2021 Apr 15 (Print Publication: 2021).
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Lausanne : Frontiers Research Foundation]
    • Subject Terms:
      Genetic Variation* ; Genome-Wide Association Study*/statistics & numerical data ; Immune Tolerance*; Autoimmune Diseases/*etiology ; Chromosome Mapping/*methods; Autoimmune Diseases/complications ; Autoimmune Diseases/genetics ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci
    • Abstract:
      The breakdown of immunological tolerance leads to autoimmune disease, and the mechanisms that maintain self-tolerance, especially in humans, are not fully understood. Genome-wide association studies (GWAS) have identified hundreds of human genetic loci statistically linked to autoimmune disease risk, and epigenetic modifications of DNA and chromatin at these loci have been associated with autoimmune disease risk. Because the vast majority of these signals are located far from genes, identifying causal variants, and their functional consequences on the correct effector genes, has been challenging. These limitations have hampered the translation of GWAS findings into novel drug targets and clinical interventions, but recent advances in understanding the spatial organization of the genome in the nucleus have offered mechanistic insights into gene regulation and answers to questions left open by GWAS. Here we discuss the potential for 'variant-to-gene mapping' approaches that integrate GWAS with 3D functional genomic data to identify human genes involved in the maintenance of tolerance.
      Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
      (Copyright © 2021 Mehra and Wells.)
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    • Contributed Indexing:
      Keywords: autoimmunity; genome-wide association studies; immune tolerance; multi-omics; single nucleotide polymorphism; variant-to-gene mapping
    • Publication Date:
      Date Created: 20210503 Date Completed: 20210916 Latest Revision: 20210916
    • Publication Date:
      20231215
    • Accession Number:
      PMC8082446
    • Accession Number:
      10.3389/fimmu.2021.633219
    • Accession Number:
      33936046