DNA methylation analysis to differentiate reference, breed, and parent-of-origin effects in the bovine pangenome era

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dc.contributor.authorMacPhillamy, C.
dc.contributor.authorChen, T.
dc.contributor.authorHiendleder, S.
dc.contributor.authorWilliams, J.L.
dc.contributor.authorAlinejad-Rokny, H.
dc.contributor.authorLow, W.Y.
dc.date.issued2024
dc.description.abstractBackground: Most DNA methylation studies have used a single reference genome with little attention paid to the bias introduced due to the reference chosen. Reference genome artifacts and genetic variation, including single nucleotide polymorphisms (SNPs) and structural variants (SVs), can lead to differences in methylation sites (CpGs) between individuals of the same species. We analyzed whole-genome bisulfite sequencing data from the fetal liver of Angus (Bos taurus taurus), Brahman (Bos taurus indicus), and reciprocally crossed samples. Using reference genomes for each breed from the Bovine Pangenome Consortium, we investigated the influence of reference genome choice on the breed and parent-of-origin effects in methylome analyses. Results: Our findings revealed that ∼75% of CpG sites were shared between Angus and Brahman, ∼5% were breed specific, and ∼20% were unresolved. We demonstrated up to ∼2% quantification bias in global methylation when an incorrect reference genome was used. Furthermore, we found that SNPs impacted CpGs 13 times more than other autosomal sites (P < 5 × 10−324) and SVs contained 1.18 times (P < 5 × 10−324) more CpGs than non-SVs. We found a poor overlap between differentially methylated regions (DMRs) and differentially expressed genes (DEGs) and suggest that DMRs may be impacting enhancers that target these DEGs. DMRs overlapped with imprinted genes, of which 1, DGAT1, which is important for fat metabolism and weight gain, was found in the breed-specific and sire-of-origin comparisons. Conclusions: This work demonstrates the need to consider reference genome effects to explore genetic and epigenetic differences accurately and identify DMRs involved in controlling certain genes.
dc.description.statementofresponsibilityCallum MacPhillamy, Tong Chen, Stefan Hiendleder, John L. Williams, Hamid Alinejad-Rokny, and Wai Yee Low
dc.identifier.citationGigaScience, 2024; 13:giae061-1-giae061-18
dc.identifier.doi10.1093/gigascience/giae061
dc.identifier.issn2047-217X
dc.identifier.issn2047-217X
dc.identifier.orcidMacPhillamy, C. [0000-0002-4057-2463]
dc.identifier.orcidChen, T. [0000-0002-7681-9632]
dc.identifier.orcidHiendleder, S. [0000-0001-6222-3240]
dc.identifier.orcidWilliams, J.L. [0000-0001-5188-7957]
dc.identifier.orcidLow, W.Y. [0000-0002-0749-765X]
dc.identifier.urihttps://hdl.handle.net/2440/143527
dc.language.isoen
dc.publisherOXFORD UNIV PRESS
dc.rights© The Author(s) 2024. Published by Oxford University Press GigaScience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://doi.org/10.1093/gigascience/giae061
dc.subjectbisulfite sequencing; methylation; CpG; structural variants; Dgat1; differentially methylated region; bovine pangenome
dc.subject.meshAnimals
dc.subject.meshCattle
dc.subject.meshBreeding
dc.subject.meshDNA Methylation
dc.subject.meshCpG Islands
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshGenome
dc.subject.meshWhole Genome Sequencing
dc.subject.meshEpigenome
dc.titleDNA methylation analysis to differentiate reference, breed, and parent-of-origin effects in the bovine pangenome era
dc.typeJournal article
pubs.publication-statusPublished

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