Evidence map›Paper›PMID 41286645›Full record

ArticleBMC genomics2025

X chromosome inactivation across primary human tissues is mostly complete, with significant implications for genetic and clinical studies.

Daniel Shriner, Ayo P Doumatey, Lin Lei, Mateus H Gouveia, Karlijn A C Meeks, Elisabeth F Heuston, Jie Zhou, Adebowale A Adeyemo, Charles N Rotimi

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In one paragraph

Article in BMC genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Daniel ShrinerCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Ayo P DoumateyCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Lin LeiCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Mateus H GouveiaCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Karlijn A C MeeksCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Elisabeth F HeustonCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Jie ZhouCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Adebowale A AdeyemoCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
Charles N RotimiCenter for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA. rotimic@mail.nih.gov.

Funding

MINORITY INTERNATIONAL RESEARCH TRAINING GRANTT37TW000041 · FIC · HOWARD UNIVERSITY · PI ADAMS-CAMPBELL, LUCILE L · 1993 to 1998
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FIC NIH HHS T37 TW000041
6 · The paper itself

Abstract

backgroundX chromosome inactivation (XCI) refers to silencing of genes on one copy of the X chromosome in XX females, resulting in dosage compensation between XX females and XY males. Genes can escape this silencing, potentially leading to sex-based differences in disease.

resultsAcross three primary tissue types, we determined XCI status by integrating whole-genome sequencing with bulk RNA-Seq data to assess allele-specific expression (ASE) at heterozygous SNPs. Across all genes and tissues, the average percentage of individuals showing escape was 4.7%. We show that models of full dosage compensation and no dosage compensation are strongly correlated over most parameter space. For G6PD deficiency, we illustrate that in G6PD*B/G6PD*A- heterozygotes, even if silencing is complete and escape is not associated with disease risk, the allele that is expressed can affect mRNA abundance.

conclusionsWith respect to studies of the genetic architecture of complex traits, our results suggest that a model of full dosage compensation, although not strictly correct for much of chromosome X, is more appropriate than a model of no dosage compensation. We conclude that uncertainty about the model of dosage compensation should not be an impediment to analysis of chromosome X in genetic epidemiology studies.

Indexed as

Chromosomes, Human, XX Chromosome InactivationAllelesDosage Compensation, GeneticFemaleHumansMaleOrgan SpecificityPolymorphism, Single NucleotideWhole Genome SequencingChromosome XDosage compensationEscapeGene expressionInactivation

Identifiers

PMID41286645
PMCPMC12751988

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.