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• W3023092931 abstract "ABSTRACT Mammalian hybrids often show striking asymmetries in their phenotypes both between reciprocal crosses, and between sexes in accordance with Haldane’s rule. Hybrid inviability is associated with parent-of-origin placental growth abnormalities for which misregulation of imprinted genes is a strong candidate mechanism. However, direct evidence for the involvement of abnormal imprinting and the mechanisms behind this proposed misregulation is limited. We used transcriptome and reduced representation bisulfite sequencing to evaluate the contribution of imprinted genes to a long-standing example of parent-of-origin placental growth dysplasia in the cross between the house mouse ( Mus musculus domesticus ) and the Algerian mouse ( Mus spretus ). We found little evidence for loss of imprinting and imprinted genes with biallelic expression were not misexpressed. Instead, imprinted genes with transgressive expression and methylation were concentrated in the Kcnq1 cluster, which contains causal genes for prenatal growth abnormalities in both mice and humans. Hypermethylation of the cluster’s imprinting control region, and consequent misexpression of the genes Phlda2 and Ascl2 , is a strong candidate mechanism for hybrid placental undergrowth. Transgressive placental and gene regulatory phenotypes, including expression and methylation in the Kcnq1 cluster, were more extreme in hybrid males. While consistent with Haldane’s rule, male-biased defects are not expected in rodent placenta because the maternal X chromosome is effectively hemizygous in both sexes. In search of an explanation we found evidence of leaky imprinted X-chromosome inactivation in hybrid females. Supplementary expression from the paternal X-chromosome may buffer the females from the effects of X-linked incompatibilities to which males are fully exposed. Sex differences in chromatin structure on the X and sex-biased maternal effects are non-mutually exclusive alternative explanations for adherence to Haldane’s rule in hybrid placenta. The results of this study contribute to understanding of the genetic basis of hybrid inviability in mammals, and the role of imprinted genes in speciation." @default.
• W3023092931 created "2020-05-13" @default.
• W3023092931 creator A5064997000 @default.
• W3023092931 creator A5066425995 @default.
• W3023092931 creator A5069723484 @default.
• W3023092931 date "2020-05-07" @default.
• W3023092931 modified "2023-09-24" @default.
• W3023092931 title "Haldane’s rule in the placenta: sex-biased misregulation of the<i>Kcnq1</i>imprinting cluster in hybrid mice" @default.
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• W3023092931 doi "https://doi.org/10.1101/2020.05.07.082248" @default.
• W3023092931 hasPublicationYear "2020" @default.
• W3023092931 type Work @default.
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