Identifying Genes Whose Mutant Transcripts Cause Dominant Disease Traits by Potential Gain-of-Function Alleles

• Published in: American journal of human genetics Vol. 103; no. 2; pp. 171 - 187
• Main Authors: Coban-Akdemir, Zeynep, White, Janson J., Song, Xiaofei, Jhangiani, Shalini N., Fatih, Jawid M., Gambin, Tomasz, Bayram, Yavuz, Chinn, Ivan K., Karaca, Ender, Punetha, Jaya, Poli, Cecilia, Boerwinkle, Eric, Shaw, Chad A., Orange, Jordan S., Gibbs, Richard A., Lappalainen, Tuuli, Lupski, James R., Carvalho, Claudia M.B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.08.2018; Elsevier
• Subjects: Alleles; antimorphic; bioinformatic tool; Codon, Nonsense - genetics; Databases, Genetic; dominant negative; Exome - genetics; frameshift alleles; Gain of Function Mutation - genetics; genotype-phenotype correlations; Humans; Mutation - genetics; NMD escape intolerance scores; NMDEscPredictor; Nonsense Mediated mRNA Decay - genetics; nonsense-mediated decay; Phenotype; stopgain variants; WES analysis; antimorphic; nonsense-mediated decay; frameshift alleles; stopgain variants; WES analysis; NMDEscPredictor; genotype-phenotype correlations; dominant negative; NMD escape intolerance scores; bioinformatic tool

Premature termination codon (PTC)-bearing transcripts are often degraded by nonsense-mediated decay (NMD) resulting in loss-of-function (LoF) alleles. However, not all PTCs result in LoF mutations, i.e., some such transcripts escape NMD and are translated to truncated peptide products that result in...