Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

• Main Authors: Marina Aznaourova, Nils Schmerer, Bernd Schmeck, Leon N. Schulte
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-11-01
• Series: Frontiers in Genetics
• Subjects: long non-coding RNA; genome-wide association study; variation (genetic); disease; single nucleotide polymorphism; mutation
• Online Access: https://www.frontiersin.org/articles/10.3389/fgene.2020.527484/full

The classic understanding of molecular disease-mechanisms is largely based on protein-centric models. During the past decade however, genetic studies have identified numerous disease-loci in the human genome that do not encode proteins. Such non-coding DNA variants increasingly gain attention in diagnostics and personalized medicine. Of particular interest are long non-coding RNA (lncRNA) genes, which generate transcripts longer than 200 nucleotides that are not translated into proteins. While most of the estimated ~20,000 lncRNAs currently remain of unknown function, a growing number of genetic studies link lncRNA gene aberrations with the development of human diseases, including diabetes, AIDS, inflammatory bowel disease, or cancer. This suggests that the protein-centric view of human diseases does not capture the full complexity of molecular patho-mechanisms, with important consequences for molecular diagnostics and therapy. This review illustrates well-documented lncRNA gene aberrations causatively linked to human diseases and discusses potential lessons for molecular disease models, diagnostics, and therapy.