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Series GSE161051 Query DataSets for GSE161051
Status Public on Nov 09, 2020
Title Haldane’s rule in the placenta: sex-biased misregulation of the Kcnq1 imprinting cluster in hybrid mice
Organisms Mus musculus domesticus; Mus spretus; Mus musculus domesticus x Mus spretus
Experiment type Methylation profiling by high throughput sequencing
Summary Hybrid phenotypes that contribute to postzygotic reproductive isolation often exhibit pronounced asymmetry, both between reciprocal crosses and between the sexes in accordance with Haldane's rule. Inviability in mammalian hybrids is associated with parent-of-origin placental growth abnormalities for which misregulation of imprinted genes is the leading candidate mechanism. However, direct evidence for the involvement of imprinted genes in hybrid growth dysplasia is limited. We used transcriptome and reduced representation bisulfite sequencing to conduct the first genome-scale assessment of the contribution of imprinted genes to parent-of-origin placental growth dysplasia in the cross between the house mouse (Mus musculus domesticus) and the Algerian mouse (Mus spretus). Imprinted genes with transgressive expression and methylation were concentrated in the Kcnq1 cluster, which contains causal genes for prenatal growth abnormalities in 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 transgressive 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 unexpected in rodent placenta because the X-chromosome is effectively hemizygous in both sexes. In search of an explanation we found evidence of leaky imprinted (paternal) X-chromosome inactivation in hybrid female placenta, an epigenetic disturbance that may buffer 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 the genetic basis of hybrid inviability in mammals, and the role of imprinted genes in speciation.
 
Overall design Analysis of 29 samples of placental DNA at e17.5 of the same pregnancies (3 groups, 4-5 biological replicates per sex, per group)
 
Contributor(s) Arévalo L, Campbell P
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Submission date Nov 08, 2020
Last update date Nov 11, 2020
Contact name Polly Campbell
E-mail(s) polly.campbell@ucr.edu
Organization name University of California Riverside
Department Evolution, Ecology, and Organismal Biology
Street address 3401 Watkins Drive
City Riverside
State/province CA
ZIP/Postal code 92521
Country USA
 
Platforms (3)
GPL26184 Illumina HiSeq 4000 (Mus musculus domesticus)
GPL26185 Illumina HiSeq 4000 (Mus spretus)
GPL26187 Illumina HiSeq 4000 (Mus musculus domesticus x Mus spretus)
Samples (29)
GSM4888949 Mus domesticus e17.5 placenta [DOM_M15_P1]
GSM4888950 Mus domesticus e17.5 placenta [DOM_M15_P2]
GSM4888951 Mus domesticus e17.5 placenta [DOM_M16_P1]
Relations
BioProject PRJNA675379
SRA SRP291640

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE161051_ASM_female.txt.gz 8.1 Kb (ftp)(http) TXT
GSE161051_ASM_male.txt.gz 8.4 Kb (ftp)(http) TXT
GSE161051_DMR_DOMvsSPRET_female.txt.gz 39.3 Kb (ftp)(http) TXT
GSE161051_DMR_DOMvsSPRET_male.txt.gz 42.6 Kb (ftp)(http) TXT
GSE161051_DMR_HYvsDOM_female.txt.gz 19.5 Kb (ftp)(http) TXT
GSE161051_DMR_HYvsDOM_male.txt.gz 30.0 Kb (ftp)(http) TXT
GSE161051_DMR_HYvsSPRET_female.txt.gz 25.0 Kb (ftp)(http) TXT
GSE161051_DMR_HYvsSPRET_male.txt.gz 28.0 Kb (ftp)(http) TXT
GSE161051_DMR_dom_MALEvsFEMALE.txt.gz 22.8 Kb (ftp)(http) TXT
GSE161051_DMR_hybrid_MALEvsFEMALE.txt.gz 20.2 Kb (ftp)(http) TXT
GSE161051_DMR_imprinted_genes_HyvsDOM_female.txt.gz 1.5 Kb (ftp)(http) TXT
GSE161051_DMR_imprinted_genes_HyvsDOM_male.txt.gz 1.6 Kb (ftp)(http) TXT
GSE161051_DMR_imprinted_genes_HyvsSPRET_female.txt.gz 1.7 Kb (ftp)(http) TXT
GSE161051_DMR_imprinted_genes_HyvsSPRET_male.txt.gz 1.6 Kb (ftp)(http) TXT
GSE161051_DMR_spret_MALEvsFEMALE.txt.gz 23.1 Kb (ftp)(http) TXT
GSE161051_RAW.tar 2.0 Gb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record
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