Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle

Prowse-Wilkins CP; Lopdell TJ; Xiang R; Vander Jagt CJ; Littlejohn MD; Chamberlain AJ; Goddard ME

Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle

dc.citation.issue	1
dc.citation.volume	23
dc.contributor.author	Prowse-Wilkins CP
dc.contributor.author	Lopdell TJ
dc.contributor.author	Xiang R
dc.contributor.author	Vander Jagt CJ
dc.contributor.author	Littlejohn MD
dc.contributor.author	Chamberlain AJ
dc.contributor.author	Goddard ME
dc.coverage.spatial	England
dc.date.accessioned	2024-10-02T22:29:00Z
dc.date.available	2024-10-02T22:29:00Z
dc.date.issued	2022-12-08
dc.description.abstract	BACKGROUND: Causal variants for complex traits, such as eQTL are often found in non-coding regions of the genome, where they are hypothesised to influence phenotypes by regulating gene expression. Many regulatory regions are marked by histone modifications, which can be assayed by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Sequence reads from ChIP-seq form peaks at putative regulatory regions, which may reflect the amount of regulatory activity at this region. Therefore, eQTL which are also associated with differences in histone modifications are excellent candidate causal variants. RESULTS: We assayed the histone modifications H3K4Me3, H3K4Me1 and H3K27ac and mRNA in the mammary gland of up to 400 animals. We identified QTL for peak height (histone QTL), exon expression (eeQTL), allele specific expression (aseQTL) and allele specific binding (asbQTL). By intersecting these results, we identify variants which may influence gene expression by altering regulatory regions of the genome, and may be causal variants for other traits. Lastly, we find that these variants are found in putative transcription factor binding sites, identifying a mechanism for the effect of many eQTL. CONCLUSIONS: We find that allele specific and traditional QTL analysis often identify the same genetic variants and provide evidence that many eQTL are regulatory variants which alter activity at regulatory regions of the bovine genome. Our work provides methodological and biological updates on how regulatory mechanisms interplay at multi-omics levels.
dc.description.confidential	false
dc.format.pagination	815-
dc.identifier.author-url	https://www.ncbi.nlm.nih.gov/pubmed/36482302
dc.identifier.citation	Prowse-Wilkins CP, Lopdell TJ, Xiang R, Vander Jagt CJ, Littlejohn MD, Chamberlain AJ, Goddard ME. (2022). Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle.. BMC Genomics. 23. 1. (pp. 815-).
dc.identifier.doi	10.1186/s12864-022-09002-9
dc.identifier.eissn	1471-2164
dc.identifier.elements-type	journal-article
dc.identifier.issn	1471-2164
dc.identifier.number	815
dc.identifier.pii	10.1186/s12864-022-09002-9
dc.identifier.uri	https://mro.massey.ac.nz/handle/10179/71578
dc.language	eng
dc.publisher	BioMed Central Ltd
dc.publisher.uri	https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-022-09002-9
dc.relation.isPartOf	BMC Genomics
dc.rights	© Crown 2022
dc.rights	CC BY 4.0
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	ChIP-seq
dc.subject	allele specific QTL
dc.subject	bovine
dc.subject	causal variants
dc.subject	function
dc.subject	histone modifications
dc.subject	molecular QTL
dc.subject	regulatory variants
dc.subject	Cattle
dc.subject	Animals
dc.subject	Histone Code
dc.subject	Multiomics
dc.subject	Genetic Variation
dc.subject	Gene Expression
dc.title	Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
dc.type	Journal article
pubs.elements-id	458529
pubs.organisational-group	Other