Rare copy-number variants (rCNVs) include deletions and duplications that occur infrequently in the global human population and can confer substantial risk for disease. Collins et al aimed to quantify the properties of haploinsufficiency (i.e., deletion intolerance) and triplosensitivity (i.e., duplication intolerance) throughout the human genome by analyzing rCNVs from nearly one million individuals to construct a genome-wide catalog of dosage sensitivity across 54 disorders, which defined 163 dosage sensitive segments associated with at least one disorder. These segments were typically gene-dense and often harbored dominant dosage sensitive driver genes. An ensemble machine learning model was built to predict dosage sensitivity probabilities (pHaplo & pTriplo) for all autosomal genes, which identified 2,987 haploinsufficient and 1,559 triplosensitive genes, including 648 that were uniquely triplosensitive.
-We want to thank DECIPHER for their support and assistance with the data. We would also like to +We would like to thank Ryan Collins for generating the data. We would also like to thank Anna Benet-Pagès for suggesting and assisting in track development and interpretation. Thank you to Luis Nassar and Jairo Navarro for the creation and release of these tracks.
We are happy to announce new GENCODE Gene annotation tracks, which correspond to Ensembl 111, for three assemblies: hg19/GRCh37, hg38/GRCh38, and mm39/GRCm39. GENCODE provides gene annotations with