From association to mechanism in complex disease genetics: the role of the 3D genome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Yao Fu, Kandice L Tessneer, Chuang Li, Patrick M Gaffney

ABSTRACT

Genome-wide association studies (GWAS) and fine mapping studies in autoimmune diseases have identified thousands of genetic variants, the majority of which are located in non-protein-coding enhancer regions. Enhancers function within the context of the three-dimensional (3D) genome to form long-range DNA looping events with target gene promoters that spatially and temporally regulate gene expression. Investigating the functional significance of GWAS variants in the context of the 3D genome is essential for mechanistic understanding of these variants and how they influence disease pathology by altering DNA looping between enhancers and the target gene promoters they regulate. In this review, we discuss the functional complexity of the 3D genome and the technological approaches used to characterize DNA looping events. We then highlight examples from the literature that illustrate how functional mapping of the 3D genome can assist in defining mechanisms that influence pathogenic gene expression. We conclude by highlighting future advances necessary to fully integrate 3D genome analyses into the functional workup of GWAS variants in the continuing effort to improve the health of patients with autoimmune diseases. More... »

PAGES

216

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-018-1721-x

DOI

http://dx.doi.org/10.1186/s13075-018-1721-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107318636

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30268153


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