Noncoding Variants as Genetic Contributors to Autoimmune Disease Pathogenesis

Ellen Javier; Xiaoming Lu; Leah C Kottyan

doi:10.1016/j.jid.2019.07.698

Noncoding Variants as Genetic Contributors to Autoimmune Disease Pathogenesis

J Invest Dermatol. 2020 Feb;140(2):277-278. doi: 10.1016/j.jid.2019.07.698.

Authors

Ellen Javier¹, Xiaoming Lu², Leah C Kottyan³

Affiliations

¹ Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address: [email protected].
² Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
³ Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA.

PMID: 31980060
DOI: 10.1016/j.jid.2019.07.698

Abstract

Understanding the functions of disease-associated noncoding variants is essential for understanding the molecular mechanisms driving diseases with a genetic cause and for identifying therapeutic targets. Combined computational and experimental analyses have demonstrated that IRF5 is hyperactivated by a pathogenic allele of TNPO3 through long-distance chromatin looping. This finding identifies a molecular mechanism contributing to the polygenic autoimmune diseases of systemic lupus erythematosus and systemic sclerosis.

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MeSH terms

Alleles
Autoimmune Diseases / genetics*
Chromatin
Humans
Interferon Regulatory Factors / genetics
Lupus Erythematosus, Systemic / genetics*
beta Karyopherins

Substances

Chromatin
IRF5 protein, human
Interferon Regulatory Factors
TNPO3 protein, human
beta Karyopherins