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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.<\/jats:p>","DOI":"10.1038\/s41467-024-53449-1","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T02:02:12Z","timestamp":1729216932000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Population variability in X-chromosome inactivation across 10 mammalian species"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9248-6420","authenticated-orcid":false,"given":"Jonathan M.","family":"Werner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-9774","authenticated-orcid":false,"given":"Jesse","family":"Gillis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"53449_CR1","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/190372a0","volume":"190","author":"MF Lyon","year":"1961","unstructured":"Lyon, M. 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