ArticleAmerican journal of human genetics2012
Deleterious- and disease-allele prevalence in healthy individuals: insights from current predictions, mutation databases, and population-scale resequencing.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Predicting Functional Effects of Synonymous Variants: A Systematic Review and Perspectives.Frontiers in genetics · 2019Pooled it
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- Monogenic diabetes: An evidence-based clinical approach.World journal of diabetes · 2025Review
- Neanderthal introgressed ancestry reveals human genomic regions enriched with recessive deleterious mutations.bioRxiv : the preprint server for biology · 2025Article
- Population-based genetic carrier screening. A consensus statement from the Spanish societies: AEGH, AEDP, ASEBIR, SEAGEN, SEF and SEGCD.European journal of human genetics : EJHG · 2025Review
- Predicted genetic burden and frequency of phenotype-associated variants in the horse.Scientific reports · 2024Article
- A method to estimate the contribution of rare coding variants to complex trait heritability.Nature communications · 2024Article
- Pathogenic variants in human DNA damage repair genes mostly arose after the latest human out-of-Africa migration.Frontiers in genetics · 2024Article
- Predisposing deleterious variants in the cancer-associated human kinases in the global populations.PloS one · 2024Article
- The Spectrum of the Heterozygous Effect in Biallelic Mendelian Diseases-The Symptomatic Heterozygote Issue.Genes · 2023Review
- ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden.Genome medicine · 2023Article
- Mitochondrial carnitine palmitoyltransferase-II dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis.World journal of gastroenterology · 2023Review
- Random allelic expression in the adult human body.Cell reports · 2023Article
- Whole Exome Sequencing Reveals a Novel Homozygous Variant in the Ganglioside Biosynthetic Enzyme,Genes · 2023Article
- A robust pipeline for ranking carrier frequencies of autosomal recessive and X-linked Mendelian disorders.NPJ genomic medicine · 2022Article
- Developmental disruption and restoration of brain synaptome architecture in the murine Pax6 neurodevelopmental disease model.Nature communications · 2022Article
- Distinct landscapes of deleterious variants in DNA damage repair system in ethnic human populations.Life science alliance · 2022Article
- Clinical validation of genomic functional screen data: Analysis of observedHGG advances · 2022Article
- Disease-specific interactome alterations via epichaperomics: the case for Alzheimer's disease.The FEBS journal · 2022Review
- Exome Sequencing Data Analysis and a Case-Control Study in Mexican Population Reveals Lipid Trait Associations of New and Known Genetic Variants in Dyslipidemia-Associated Loci.Frontiers in genetics · 2022Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
We have assessed the numbers of potentially deleterious variants in the genomes of apparently healthy humans by using (1) low-coverage whole-genome sequence data from 179 individuals in the 1000 Genomes Pilot Project and (2) current predictions and databases of deleterious variants. Each individual carried 281-515 missense substitutions, 40-85 of which were homozygous, predicted to be highly damaging. They also carried 40-110 variants classified by the Human Gene Mutation Database (HGMD) as disease-causing mutations (DMs), 3-24 variants in the homozygous state, and many polymorphisms putatively associated with disease. Whereas many of these DMs are likely to represent disease-allele-annotation errors, between 0 and 8 DMs (0-1 homozygous) per individual are predicted to be highly damaging, and some of them provide information of medical relevance. These analyses emphasize the need for improved annotation of disease alleles both in mutation databases and in the primary literature; some HGMD mutation data have been recategorized on the basis of the present findings, an iterative process that is both necessary and ongoing. Our estimates of deleterious-allele numbers are likely to be subject to both overcounting and undercounting. However, our current best mean estimates of ~400 damaging variants and ~2 bona fide disease mutations per individual are likely to increase rather than decrease as sequencing studies ascertain rare variants more effectively and as additional disease alleles are discovered.
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