气候变化领域集成服务门户(CCPortal): Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance

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DOI	10.1073/pnas.2001248118
	Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance
	Rapaport F.; Boisson B.; Gregor A.; Béziat V.; Boisson-Dupuis S.; Bustamante J.; Jouanguy E.; Puel A.; Rosain J.; Zhang Q.; Zhang S.-Y.; Gleeson J.G.; Quintana-Murci L.; Casanova J.-L.; Abel L.; Patin E.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Genetic variants underlying life-threatening diseases, being unlikely to be transmitted to the next generation, are gradually and selectively eliminated from the population through negative selection. We study the determinants of this evolutionary process in human genes underlying monogenic diseases by comparing various negative selection scores and an integrative approach, CoNeS, at 366 loci underlying inborn errors of immunity (IEI). We find that genes underlying autosomal dominant (AD) or X-linked IEI have stronger negative selection scores than those underlying autosomal recessive (AR) IEI, whose scores are not different from those of genes not known to be disease causing. Nevertheless, genes underlying AR IEI that are lethal before reproductive maturity with complete penetrance have stronger negative selection scores than other genes underlying AR IEI. We also show that genes underlying AD IEI by loss of function have stronger negative selection scores than genes underlying AD IEI by gain of function, while genes underlying AD IEI by haploinsufficiency are under stronger negative selection than other genes underlying AD IEI. These results are replicated in 1,140 genes underlying inborn errors of neurodevelopment. Finally, we propose a supervised classifier, SCoNeS, which predicts better than state-of-the-art approaches whether a gene is more likely to underlie an AD or AR disease. The clinical outcomes of monogenic inborn errors, together with their mode and mechanisms of inheritance, determine the levels of negative selection at their corresponding loci. Integrating scores of negative selection may facilitate the prioritization of candidate genes and variants in patients suspected to carry an inborn error. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Immunodeficiency \| selection \| evolution \| genetics \| method
语种	英语
scopus关键词	Article; autosomal dominant inheritance; autosomal recessive disorder; controlled study; disease severity; female; gain of function mutation; gene locus; gene replication; genetic selection; genetic variability; haploinsufficiency; human; inborn error of metabolism; inheritance; loss of function mutation; male; nerve cell differentiation; prediction; priority journal; X chromosome linked disorder
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180969
作者单位	St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, United States; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, 75015, France; University of Paris, Imagine Institute, Paris, 75015, France; Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, 91054, Germany; Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique–Hôpitaux de Paris, Paris, 75015, France; Howard Hughes Medical Institute, San diego, CA 92093, United States; Rady Children’s Institute of Genomic Medicine, Department of Neurosciences, University of California San Diego, San diego, CA 92093, United States; Laboratory for Pediatric Brain Disease, Rockefeller University, New York, NY 10065, United States; Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, CNRS, Paris, 75015, France; Chair of H...
推荐引用方式 GB/T 7714	Rapaport F.,Boisson B.,Gregor A.,et al. Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance[J],2021,118(3).
APA	Rapaport F..,Boisson B..,Gregor A..,Béziat V..,Boisson-Dupuis S..,...&Patin E..(2021).Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Rapaport F.,et al."Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).