Defining Essential Regions of the Human Genome

Update item information
Identifier defining_essential_regions_of_the_human_genome
Title Defining Essential Regions of the Human Genome
Creator Quinlan, A.R.; Human Genetics; School of Medicine; University of Utah Health
Subject Diffusion of Innovation; Genome, Human; Human Genome Project; Exome; Nucleotides; Genetic Variation; Chromosome Mapping; Mutation; DNA Mutational Analysis; Developmental Disabilities; Datasets as Topic; Genetic Association Studies; Knowledge Discovery
Keyword Genomics
Image Caption Patterns of genetic variation (depicted as colored dots) from >120,000 humans revealed constrained coding regions within genes where variation does not occur in healthy individuals.
Description There is a longstanding interest in identifying the subset of our genome that is the most essential to life and normal development. Such regions should be under the highest purifying selection, and therefore, exhibit lower nucleotide diversity. In the case of protein-coding genes, especially strong "constraint" should be observed against protein-altering (i.e., missense, stop-gain, frameshift, etc.) variants. Prior studies have attempted to identify constrained genes, but have been unable to identify focal regions of constraint within each gene: in other words, which specific regions of protein genes are most intolerant, and therefore most likely to cause disease when mutated? To address this question, Quinlan and colleagues studied genetic variation detected among >120,000 human exomes to reveal focal coding regions that lack variation in healthy individuals. These "constrained coding regions" (CCRs) are inferred to be under strong purifying selection and are enriched for known pathogenic variants. Perhaps the most intriguing aspect of this map of CCRs is the fact than many of the most constrained regions lie within genes that lacked prior disease association. Thus, these regions hold the promise of new disease gene discovery in the context of developmental disorders and are used to prioritize mutations in rare human diseases.
Relation is Part of 50 Basic Science Discoveries in 5 Years- 2019
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Date Digital 2020
Date 2019
Type Image
Format image/jpeg
Rights Management Copyright © 2020, University of Utah, All Rights Reserved
Language eng
ARK ark:/87278/s6f53c73
References 1.) A map of constrained coding regions in the human genome. Havrilla JM, Pedersen BS, Layer RM, Quinlan AR. Nat Genet. 2019 Jan;51(1):88 (cover article). https://pubmed.ncbi.nlm.nih.gov/30531870/
Press Releases and Media Big Datasets Pinpoint New Regions to Explore the Genome for Disease https://healthcare.utah.edu/publicaffairs/news/2018/12/quinlan-model.php; GenomeWeb; MedicalXpress; Health News Digest http://www.healthnewsdigest.com/news/Disease_420/Big-Datasets-Pinpoint-New-Regions-to-Explore-the-Genome-for-Disease.shtml.
Setname ehsl_50disc
Date Created 2020-08-13
Date Modified 2020-11-17
ID 1589367
Reference URL https://collections.lib.utah.edu/ark:/87278/s6f53c73