ArticleMolecular biology and evolution2016
Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide meta-analysis identifies genetic risk loci for mono- and polyneuropathies in 983 477 individuals.Human molecular genetics · 2026Pooled it
- Immunological Determinants of Oncogenic Virus-Driven Cancers in Africa: Mechanisms, Co-Infections and Public Health Challenges.Pathogens (Basel, Switzerland) · 2026Review
- Haplotype-resolved assemblies of the MHC region in five widely used tumor cell lines.Genes & diseases · 2025Article
- Haplotype analysis reveals pleiotropic disease associations in the HLA region.American journal of human genetics · 2025Article
- Pathogen Adaptation of HLA Alleles and Its Correlation with Autoimmune Diseases in the Han Chinese.Genomics, proteomics & bioinformatics · 2025Article
- Complete sequencing of ape genomes.Nature · 2025Article
- Human leukocyte antigen variation is associated with cytomegalovirus serostatus in healthy individuals.American journal of human genetics · 2025Article
- MHConstructor: a high-throughput, haplotype-informed solution to the MHC assembly challenge.Genome biology · 2024Article
- Complete sequencing of ape genomes.bioRxiv : the preprint server for biology · 2024Article
- Article
- MHConstructor: A high-throughput, haplotype-informed solution to the MHC assembly challenge.bioRxiv : the preprint server for biology · 2024Article
- Narrative Review Explaining the Role ofInfectious disease reports · 2024Review
- The Impact of Patterns in Linkage Disequilibrium and Sequencing Quality on the Imprint of Balancing Selection.Genome biology and evolution · 2024Article
- HLA Genes: A Hallmark of Functional Genetic Variation and Complex Evolution.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Article
- Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution.Nature genetics · 2023Article
- JTK: targeted diploid genome assembler.Bioinformatics (Oxford, England) · 2023Article
- Enabling interpretable machine learning for biological data with reliability scores.PLoS computational biology · 2023Article
- Mapping the dynamic genetic regulatory architecture ofmedRxiv : the preprint server for health sciences · 2023Article
- Relating pathogenic loss-of-function mutations in humans to their evolutionary fitness costs.eLife · 2023Article
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Abstract
Deleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are maintained at considerable frequencies. Here, we test the hypothesis that balancing selection may counteract purifying selection in neighboring regions and thus maintain deleterious variants at higher frequency than expected from their detrimental fitness effect. We first show in realistic simulations that balancing selection reduces the density of polymorphic sites surrounding a locus under balancing selection, but at the same time markedly increases the population frequency of the remaining variants, including even substantially deleterious alleles. To test the predictions of our simulations empirically, we then use whole-exome sequencing data from 6,500 human individuals and focus on the most established example for balancing selection in the human genome, the major histocompatibility complex (MHC). Our analysis shows an elevated frequency of putatively deleterious coding variants in nonhuman leukocyte antigen (non-HLA) genes localized in the MHC region. The mean frequency of these variants declined with physical distance from the classical HLA genes, indicating dependency on genetic linkage. These results reveal an indirect cost of the genetic diversity maintained by balancing selection, which has hitherto been perceived as mostly advantageous, and have implications both for the evolution of recombination and also for the epidemiology of various MHC-associated diseases.
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