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Population variability in X-chromosome inactivation across 10 mammalian species

Author

Listed:
  • Jonathan M. Werner

    (Cold Spring Harbor Laboratory
    University of Toronto)

  • John Hover

    (Cold Spring Harbor Laboratory)

  • Jesse Gillis

    (Cold Spring Harbor Laboratory
    University of Toronto)

Abstract

One of the two X-chromosomes in female mammals is epigenetically silenced in embryonic stem cells by X-chromosome inactivation. This creates a mosaic of cells expressing either the maternal or the paternal X allele. The X-chromosome inactivation ratio, the proportion of inactivated parental alleles, varies widely among individuals, representing the largest instance of epigenetic variability within mammalian populations. While various contributing factors to X-chromosome inactivation variability are recognized, namely stochastic and/or genetic effects, their relative contributions are poorly understood. This is due in part to limited cross-species analysis, making it difficult to distinguish between generalizable or species-specific mechanisms for X-chromosome inactivation ratio variability. To address this gap, we measure X-chromosome inactivation ratios in ten mammalian species (9531 individual samples), ranging from rodents to primates, and compare the strength of stochastic models or genetic factors for explaining X-chromosome inactivation variability. Our results demonstrate the embryonic stochasticity of X-chromosome inactivation is a general explanatory model for population X-chromosome inactivation variability in mammals, while genetic factors play a minor role.

Suggested Citation

  • Jonathan M. Werner & John Hover & Jesse Gillis, 2024. "Population variability in X-chromosome inactivation across 10 mammalian species," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53449-1
    DOI: 10.1038/s41467-024-53449-1
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    References listed on IDEAS

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    1. Ikuhiro Okamoto & Catherine Patrat & Dominique Thépot & Nathalie Peynot & Patricia Fauque & Nathalie Daniel & Patricia Diabangouaya & Jean-Philippe Wolf & Jean-Paul Renard & Véronique Duranthon & Edit, 2011. "Erratum: Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development," Nature, Nature, vol. 474(7350), pages 239-240, June.
    2. Ikuhiro Okamoto & Catherine Patrat & Dominique Thépot & Nathalie Peynot & Patricia Fauque & Nathalie Daniel & Patricia Diabangouaya & Jean-Philippe Wolf & Jean-Paul Renard & Véronique Duranthon & Edit, 2011. "Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development," Nature, Nature, vol. 472(7343), pages 370-374, April.
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