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A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes.

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Title: A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes.
Authors: MacArthur, Daniel G., Balasubramanian, Suganthi, Frankish, Adam, Ni Huang, Morris, James, Walter, Klaudia, Jostins, Luke, Habegger, Lukas, Pickrell, Joseph K., Montgomery, Stephen B., Albers, Cornelis A., Zhang, Zhengdong D., Conrad, Donald F., Lunter, Gerton, Hancheng Zheng, Ayub, Qasim, DePristo, Mark A., Banks, Eric, Min Hu, Handsaker, Robert E.
Source: Science (pre-March 2025). 2/17/2012, Vol. 335 Issue 6070, p823-828. 6p.
Subjects: Human genome, Human gene mapping, Genes, Proteins, Alleles, Natural selection, Phenotypes
Abstract: Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: <searchLink fieldCode="AR" term="%22MacArthur%2C+Daniel+G%2E%22">MacArthur, Daniel G.</searchLink><br /><searchLink fieldCode="AR" term="%22Balasubramanian%2C+Suganthi%22">Balasubramanian, Suganthi</searchLink><br /><searchLink fieldCode="AR" term="%22Frankish%2C+Adam%22">Frankish, Adam</searchLink><br /><searchLink fieldCode="AR" term="%22Ni+Huang%22">Ni Huang</searchLink><br /><searchLink fieldCode="AR" term="%22Morris%2C+James%22">Morris, James</searchLink><br /><searchLink fieldCode="AR" term="%22Walter%2C+Klaudia%22">Walter, Klaudia</searchLink><br /><searchLink fieldCode="AR" term="%22Jostins%2C+Luke%22">Jostins, Luke</searchLink><br /><searchLink fieldCode="AR" term="%22Habegger%2C+Lukas%22">Habegger, Lukas</searchLink><br /><searchLink fieldCode="AR" term="%22Pickrell%2C+Joseph+K%2E%22">Pickrell, Joseph K.</searchLink><br /><searchLink fieldCode="AR" term="%22Montgomery%2C+Stephen+B%2E%22">Montgomery, Stephen B.</searchLink><br /><searchLink fieldCode="AR" term="%22Albers%2C+Cornelis+A%2E%22">Albers, Cornelis A.</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Zhengdong+D%2E%22">Zhang, Zhengdong D.</searchLink><br /><searchLink fieldCode="AR" term="%22Conrad%2C+Donald+F%2E%22">Conrad, Donald F.</searchLink><br /><searchLink fieldCode="AR" term="%22Lunter%2C+Gerton%22">Lunter, Gerton</searchLink><br /><searchLink fieldCode="AR" term="%22Hancheng+Zheng%22">Hancheng Zheng</searchLink><br /><searchLink fieldCode="AR" term="%22Ayub%2C+Qasim%22">Ayub, Qasim</searchLink><br /><searchLink fieldCode="AR" term="%22DePristo%2C+Mark+A%2E%22">DePristo, Mark A.</searchLink><br /><searchLink fieldCode="AR" term="%22Banks%2C+Eric%22">Banks, Eric</searchLink><br /><searchLink fieldCode="AR" term="%22Min+Hu%22">Min Hu</searchLink><br /><searchLink fieldCode="AR" term="%22Handsaker%2C+Robert+E%2E%22">Handsaker, Robert E.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 2/17/2012, Vol. 335 Issue 6070, p823-828. 6p.
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  Data: <searchLink fieldCode="DE" term="%22Human+genome%22">Human genome</searchLink><br /><searchLink fieldCode="DE" term="%22Human+gene+mapping%22">Human gene mapping</searchLink><br /><searchLink fieldCode="DE" term="%22Genes%22">Genes</searchLink><br /><searchLink fieldCode="DE" term="%22Proteins%22">Proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Alleles%22">Alleles</searchLink><br /><searchLink fieldCode="DE" term="%22Natural+selection%22">Natural selection</searchLink><br /><searchLink fieldCode="DE" term="%22Phenotypes%22">Phenotypes</searchLink>
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  Data: Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=72661433
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