ArticlePLoS genetics2008
Role of duplicate genes in robustness against deleterious human mutations.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 100 citations in OpenAlex.
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- Intrafamilial phenotypic variability in hypophosphatasia: evidence from two families and the literature.Frontiers in endocrinology · 2026Review
- Methods, applications, and computational challenges in bait capture enrichment.Cell reports methods · 2025Review
- Human genetic variation reveals FCRL3 is a lymphocyte receptor for Yersinia pestis.Cell genomics · 2025Article
- Mitochondrial Genome Analysis ofEcology and evolution · 2025Article
- Functional implications of paralog genes in polyglutamine spinocerebellar ataxias.Human genetics · 2023Review
- The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation.Nature communications · 2023Article
- Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism.Journal of biomedical science · 2023Review
- A Simple Evolutionary Model of Genetic Robustness After Gene Duplication.Journal of molecular evolution · 2022Article
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- The Pathophysiology of Rett Syndrome With a Focus on Breathing Dysfunctions.Physiology (Bethesda, Md.) · 2020Review
- Phosphoglycerate kinase: structural aspects and functions, with special emphasis on the enzyme from Kinetoplastea.Open biology · 2020Review
- Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development.Cellular and molecular life sciences : CMLS · 2020Article
- Similarities in biological processes can be used to bridge ecology and molecular biology.Evolutionary applications · 2020Article
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- Paralog dependency indirectly affects the robustness of human cells.Molecular systems biology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is now widely recognized that robustness is an inherent property of biological systems [1],[2],[3]. The contribution of close sequence homologs to genetic robustness against null mutations has been previously demonstrated in simple organisms [4],[5]. In this paper we investigate in detail the contribution of gene duplicates to back-up against deleterious human mutations. Our analysis demonstrates that the functional compensation by close homologs may play an important role in human genetic disease. Genes with a 90% sequence identity homolog are about 3 times less likely to harbor known disease mutations compared to genes with remote homologs. Moreover, close duplicates affect the phenotypic consequences of deleterious mutations by making a decrease in life expectancy significantly less likely. We also demonstrate that similarity of expression profiles across tissues significantly increases the likelihood of functional compensation by homologs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.