Cellular network perturbations by disease-associated variants. Issue 3 (June 2017)

• Record Type: Journal Article
• Authors: Sewell, Jared A.; Fuxman Bass, Juan I.
• Is Part Of: Current opinion in systems biology. Issue 3(2017)
• Page Start: 60
• Page End: 66
• Publication Date: 2017-06
• Subjects: Systems biology -- Periodicals; 570
• DOI: 10.1016/j.coisb.2017.04.009
• Languages: English
• ISSNs: 2452-3100

Abstract

Abstract: Genetic and genome-wide association studies (GWAS) have identified a myriad of human disease-associated genomic variants. However, these studies do not reveal the mechanisms by which these variants perturb cellular networks, a necessary step to intervene and improve disease outcomes. This has been challenging because multiple variants are present in haplotype blocks, thereby confounding the identification of causal variants, and because most reside in noncoding regions. Here, we review recent advances in the identification of functional variants and gene-variant associations. In addition, we examine approaches used to study perturbations in protein–protein and protein–DNA interactions associated with disease, and discuss how these perturbations affect cellular networks. Graphical abstract: Highlights: Disease variants affect cellular networks disrupting coding and noncoding regions. Coding variants affect protein activity and perturb cellular interactions. Noncoding variants affect TF binding and epigenetic marks, altering gene expression. Network mapping of variants can inform on mechanisms and improve disease therapies.