ArticleEuropean journal of human genetics : EJHG2019
Skewed X-inactivation is common in the general female population.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- ATR-X syndrome: genetics, clinical spectrum, and management.Human genetics · 2021Pooled it
- X chromosome-wide association studies for quantitative trait loci based on the mixture of general pedigrees and additional unrelated individuals.Briefings in bioinformatics · 2026Article
- Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms.Biochemical Society transactions · 2026Review
- The genotypic and phenotypic landscape of PDHA1-related pyruvate dehydrogenase complex deficiency.Brain : a journal of neurology · 2026Article
- X-Linked Intellectual Developmental Disorder-93 Caused by BRWD3 Mutation in Females: A Case Report and Literature Review.Molecular genetics & genomic medicine · 2026Review
- The impact of sex on the immune system explored at the single-cell level.American journal of human genetics · 2026Article
- Hemophilia's Overlooked Female Face.Journal of clinical medicine · 2026Review
- The Cardiovascular Manifestations and Management Recommendations for Ogden Syndrome.Pediatric cardiology · 2026Article
- The type 1 and type 3 immune responses underlying the tissue inflammation associated with NOX2 deficiency.Frontiers in immunology · 2026Review
- Genomic Instability and Clonal Hematopoiesis in the Deep-Space Environment: The Role of Sex-Chromosome Asymmetry and High-LET Radiation.Current stem cell reports · 2026Article
- Intergenerational neuroimaging's present and future: Considering sex as a biological variable to enhance knowledge of brain development through parent-offspring similarity.Developmental cognitive neuroscience · 2025Review
- Whole-Body Skeletal Muscle MRI Patterns in Female Dystrophinopathy Carriers.Neurology. Genetics · 2025Article
- Decoding splicing complexity: integrated genomic analysis reveals two novel pathogenic variants in Chinese dystrophinopathy pedigrees.Genes & genomics · 2025Article
- Mechanisms Underlying Treatment-Resistant Depression: Exploring Sex-Based Biological Differences.Journal of neurochemistry · 2025Review
- Article
- X-chromosome-wide association study for Alzheimer's disease.Molecular psychiatry · 2025Article
- Genetic analysis of a female patient with X-linked lymphoproliferative disease type 2: a case report.Journal of medical case reports · 2025Article
- Optical genome mapping identifies rare structural variants in neural tube defects.Genome research · 2025Article
- X-Linked Gene Dosage and SOX2 Act as Key Roadblocks for Human Germ Cell Specification in Klinefelter Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants.
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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.