The Characteristics of Heterozygous Protein Truncating Variants in the Human Genome

Sequencing projects have identified large numbers of rare stop-gain and frameshift variants in the human genome. As most of these are observed in the heterozygous state, they test a gene's tolerance to haploinsufficiency and dominant loss of function. We analyzed the distribution of truncating...

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Veröffentlicht in:	PLoS computational biology 2015-12, Vol.11 (12), p.e1004647-e1004647
Hauptverfasser:	Bartha, István, Rausell, Antonio, McLaren, Paul J, Mohammadi, Pejman, Tardaguila, Manuel, Chaturvedi, Nimisha, Fellay, Jacques, Telenti, Amalio
Format:	Artikel
Sprache:	eng
Schlagworte:	Base Sequence Chromosome Mapping - methods Codon, Nonsense - genetics Estimates Funding Genes Genetic Variation - genetics Genome, Human - genetics Genomes Humans Molecular Sequence Data Monte Carlo simulation Mutation Proteins Proteins - genetics
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Beschreibung
Zusammenfassung:	Sequencing projects have identified large numbers of rare stop-gain and frameshift variants in the human genome. As most of these are observed in the heterozygous state, they test a gene's tolerance to haploinsufficiency and dominant loss of function. We analyzed the distribution of truncating variants across 16,260 autosomal protein coding genes in 11,546 individuals. We observed 39,893 truncating variants affecting 12,062 genes, which significantly differed from an expectation of 12,916 genes under a model of neutral de novo mutation (p
ISSN:	1553-7358 1553-734X 1553-7358
DOI:	10.1371/journal.pcbi.1004647