ArticleGenetics2021
Bayesian modeling of skewed X inactivation in genetically diverse mice identifies a novel Xce allele associated with copy number changes.
Article in Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- KDM6A facilitates Xist upregulation at the onset of X inactivation.Biology of sex differences · 2025Article
- Population variability in X-chromosome inactivation across 10 mammalian species.Nature communications · 2024Article
- Population variability in X-chromosome inactivation across 9 mammalian species.bioRxiv : the preprint server for biology · 2023Article
- Which mouse multiparental population is right for your study? The Collaborative Cross inbred strains, their F1 hybrids, or the Diversity Outbred population.G3 (Bethesda, Md.) · 2023Article
- Variability of cross-tissue X-chromosome inactivation characterizes timing of human embryonic lineage specification events.Developmental cell · 2022Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Female mammals are functional mosaics of their parental X-linked gene expression due to X chromosome inactivation (XCI). This process inactivates one copy of the X chromosome in each cell during embryogenesis and that state is maintained clonally through mitosis. In mice, the choice of which parental X chromosome remains active is determined by the X chromosome controlling element (Xce), which has been mapped to a 176-kb candidate interval. A series of functional Xce alleles has been characterized or inferred for classical inbred strains based on biased, or skewed, inactivation of the parental X chromosomes in crosses between strains. To further explore the function structure basis and location of the Xce, we measured allele-specific expression of X-linked genes in a large population of F1 females generated from Collaborative Cross (CC) strains. Using published sequence data and applying a Bayesian "Pólya urn" model of XCI skew, we report two major findings. First, inter-individual variability in XCI suggests mouse epiblasts contain on average 20-30 cells contributing to brain. Second, CC founder strain NOD/ShiLtJ has a novel and unique functional allele, Xceg, that is the weakest in the Xce allelic series. Despite phylogenetic analysis confirming that NOD/ShiLtJ carries a haplotype almost identical to the well-characterized C57BL/6J (Xceb), we observed unexpected patterns of XCI skewing in females carrying the NOD/ShiLtJ haplotype within the Xce. Copy number variation is common at the Xce locus and we conclude that the observed allelic series is a product of independent and recurring duplications shared between weak Xce alleles.
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