title: Differentially Expressed Genes in Endometrium and Corpus Luteum of Holstein Cows Selected for High and Low Fertility Are Enriched for Sequence Variants Associated with Fertility.
abstract: Despite the importance of fertility in humans and livestock, there has been little success dissecting the genetic basis of fertility. Our hypothesis was that genes differentially expressed in the endometrium and corpus luteum on Day 13 of the estrous cycle between cows with either good or poor genetic merit for fertility would be enriched for genetic variants associated with fertility. We combined a unique genetic model of fertility (cattle that have been selected for high and low fertility and show substantial difference in fertility) with gene expression data from these cattle and genome-wide association study (GWAS) results in ∼20,000 cattle to identify quantitative trait loci (QTL) regions and sequence variants associated with genetic variation in fertility. Two hundred and forty-five QTL regions and 17 sequence variants associated primarily with prostaglandin F2alpha, steroidogenesis, mRNA processing, energy status, and immune-related processes were identified. Ninety-three of the QTL regions were validated by two independent GWAS, with signals for fertility detected primarily on chromosomes 18, 5, 7, 8, and 29. Plausible causative mutations were identified, including one missense variant significantly associated with fertility and predicted to affect the protein function of EIF4EBP3. The results of this study enhance our understanding of 1) the contribution of the endometrium and corpus luteum transcriptome to phenotypic fertility differences and 2) the genetic architecture of fertility in dairy cattle. Including these variants in predictions of genomic breeding values may improve the rate of genetic gain for this critical trait.
authors.affiliation: Animal and Grassland Research and Innovation Centre, Teagasc, Moorepark, Fermoy, County Cork, Ireland School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Moore
authors.affiliation: Department of Economic Development, Jobs, Transport and Resources & Dairy Futures Cooperative Research Centre, Agribio, La Trobe University, Bundoora, Australia.
authors.forename: Jennie E
authors.initials: JE
authors.lastname: Pryce
authors.affiliation: Department of Economic Development, Jobs, Transport and Resources & Dairy Futures Cooperative Research Centre, Agribio, La Trobe University, Bundoora, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Hayes
authors.affiliation: Department of Economic Development, Jobs, Transport and Resources & Dairy Futures Cooperative Research Centre, Agribio, La Trobe University, Bundoora, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Chamberlain
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Australia.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Kemper
authors.affiliation: Animal and Grassland Research and Innovation Centre, Teagasc, Moorepark, Fermoy, County Cork, Ireland.
authors.forename: Donagh P
authors.initials: DP
authors.lastname: Berry
authors.affiliation: Animal and Grassland Research and Innovation Centre, Teagasc, Grange, Dunsany, County Meath, Ireland.
authors.forename: Matt
authors.initials: M
authors.lastname: McCabe
authors.affiliation: Animal and Grassland Research and Innovation Centre, Teagasc, Grange, Dunsany, County Meath, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Cormican
authors.affiliation: School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Pat
authors.initials: P
authors.lastname: Lonergan
authors.affiliation: School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Trudee
authors.initials: T
authors.lastname: Fair
authors.affiliation: Animal and Grassland Research and Innovation Centre, Teagasc, Moorepark, Fermoy, County Cork, Ireland stephen.butler@teagasc.ie.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Butler
mesh_terms: D000818:Animals; D002417:Cattle; D002875:Chromosomes / Q000235:genetics; D003338:Corpus Luteum / Q000378:metabolism*; D015237:Dinoprost / Q000096:biosynthesis / Q000235:genetics; D004717:Endometrium / Q000378:metabolism / Q000502:physiology; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics* / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics* / Q000502:physiology*; D055106:Genome-Wide Association Study; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D059467:Transcriptome
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D012333:RNA, Messenger; D015237:Dinoprost
keywords: corpus luteum; differentially expressed genes; endometrium; fertility; genetic merit; genome-wide association; transcriptomics; variants