ReviewNPJ genomic medicine2019
Gene discovery informatics toolkit defines candidate genes for unexplained infertility and prenatal or infantile mortality.
Review in NPJ genomic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The genetic architecture of sporadic and multiple consecutive miscarriage.Nature communications · 2020Pooled it
- Article
- A severe neurodevelopmental syndrome linked to a South Asian founder variant in the UFMylation adaptor CDK5RAP3.Acta neuropathologica · 2026Article
- Integrating 730,947 exome sequences with clinical literature improves gene discovery.medRxiv : the preprint server for health sciences · 2026Article
- Characterisation of Urine-Derived Cells for the Molecular Diagnosis of Rare Disorders.International journal of molecular sciences · 2026Article
- Expanded Carrier Screening: Current Evidence and Future Directions in the Era of Population Genomics.Genes · 2026Review
- Genomics of pregnancy loss.Journal of assisted reproduction and genetics · 2026Review
- Genetic Variants in Recurrent Euploid Pregnancy Loss.medRxiv : the preprint server for health sciences · 2025Article
- Lethal phenotypes in Mendelian disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Computational identification of disease models through cross-species phenotype comparison.Disease models & mechanisms · 2024Article
- Improving prenatal diagnosis through standards and aggregation.Prenatal diagnosis · 2024Review
- Miscarriage risk assessment: a bioinformatic approach to identifying candidate lethal genes and variants.Human genetics · 2024Article
- Lethal phenotypes in Mendelian disorders.medRxiv : the preprint server for health sciences · 2024Article
- Biallelic ATP2B1 variants as a likely cause of a novel neurodevelopmental malformation syndrome with primary hypoparathyroidism.European journal of human genetics : EJHG · 2024Article
- Essential genes: a cross-species perspective.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Why do humans need thrombospondin-1?Journal of cell communication and signaling · 2023Review
- Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality.Nature communications · 2023Article
- Prevalence, parameters, and pathogenic mechanisms for splice-altering acceptor variants that disrupt the AG exclusion zone.HGG advances · 2022Article
- Mendelian gene identification through mouse embryo viability screening.Genome medicine · 2022Article
- The sequences of 150,119 genomes in the UK Biobank.Nature · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite a recent surge in novel gene discovery, genetic causes of prenatal-lethal phenotypes remain poorly defined. To advance gene discovery in prenatal-lethal disorders, we created an easy-to-mine database integrating known human phenotypes with inheritance pattern, scores of genetic constraint, and murine and cellular knockout phenotypes-then critically assessed defining features of known prenatal-lethal genes, among 3187 OMIM genes, and relative to 16,009 non-disease genes. While around one-third (39%) of protein-coding genes are essential for murine development, we curate only 3% (624) of human protein-coding genes linked currently to prenatal/infantile lethal disorders. 75% prenatal-lethal genes are linked to developmental lethality in knockout mice, compared to 54% for all OMIM genes and 34% among non-disease genes. Genetic constraint correlates with inheritance pattern (autosomal recessive <<autosomal dominant <X-linked), and is greatest among prenatal-lethal genes. Importantly, >90% of recessive genes show neither missense nor loss-of-function constraint, even for prenatal-lethal genes. Detailed ontology mapping for 624 prenatal-lethal genes shows marked enrichment among dominant genes for nuclear proteins with roles in RNA/DNA biology, with recessive genes enriched in cytoplasmic (mitochondrial) metabolic proteins. We conclude that genes without genetic constraint should not be excluded as potential novel disease genes, and especially for recessive conditions (<10% constrained). Prenatal lethal genes are 5.9-fold more likely to be associated with a lethal murine phenotype than non-disease genes. Cell essential genes are largely a subset of mouse-lethal genes, notably under-represented among known OMIM genes, and strong candidates for gamete/embryo non-viability. We therefore curate 3435 'candidate developmental lethal' human genes: essential for murine development or cellular viability, not yet linked to human disorders, presenting strong candidates for unexplained infertility and prenatal/infantile mortality.
Identifiers
What OpenQuestion holds
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.