A new mechanism for a familiar mutation - bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement

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dc.citation.issue1
dc.citation.volume21
dc.contributor.authorFink T
dc.contributor.authorLopdell TJ
dc.contributor.authorTiplady K
dc.contributor.authorHandley R
dc.contributor.authorJohnson TJJ
dc.contributor.authorSpelman RJ
dc.contributor.authorDavis SR
dc.contributor.authorSnell RG
dc.contributor.authorLittlejohn MD
dc.coverage.spatialEngland
dc.date.accessioned2024-07-04T02:45:04Z
dc.date.available2024-07-04T02:45:04Z
dc.date.issued2020-08-26
dc.description.abstractBACKGROUND: The DGAT1 gene encodes an enzyme responsible for catalysing the terminal reaction in mammary triglyceride synthesis, and underpins a well-known pleiotropic quantitative trait locus (QTL) with a large influence on milk composition phenotypes. Since first described over 15 years ago, a protein-coding variant K232A has been assumed as the causative variant underlying these effects, following in-vitro studies that demonstrated differing levels of triglyceride synthesis between the two protein isoforms. RESULTS: We used a large RNAseq dataset to re-examine the underlying mechanisms of this large milk production QTL, and hereby report novel expression-based functions of the chr14 g.1802265AA > GC variant that encodes the DGAT1 K232A substitution. Using expression QTL (eQTL) mapping, we demonstrate a highly-significant mammary eQTL for DGAT1, where the K232A mutation appears as one of the top associated variants for this effect. By conducting in vitro expression and splicing experiments in bovine mammary cell culture, we further show modulation of splicing efficiency by this mutation, likely through disruption of an exon splice enhancer as a consequence of the allele encoding the 232A variant. CONCLUSIONS: The relative contributions of the enzymatic and transcription-based mechanisms now attributed to K232A remain unclear; however, these results suggest that transcriptional impacts contribute to the diversity of lactation effects observed at the DGAT1 locus.
dc.description.confidentialfalse
dc.format.pagination591-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/32847516
dc.identifier.citationFink T, Lopdell TJ, Tiplady K, Handley R, Johnson TJJ, Spelman RJ, Davis SR, Snell RG, Littlejohn MD. (2020). A new mechanism for a familiar mutation - bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement.. BMC Genomics. 21. 1. (pp. 591-).
dc.identifier.doi10.1186/s12864-020-07004-z
dc.identifier.eissn1471-2164
dc.identifier.elements-typejournal-article
dc.identifier.issn1471-2164
dc.identifier.numberARTN 591
dc.identifier.pii10.1186/s12864-020-07004-z
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/70084
dc.languageeng
dc.publisherBioMed Central Ltd
dc.publisher.urihttps://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-020-07004-z
dc.relation.isPartOfBMC Genomics
dc.rights(c) 2020 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCattle
dc.subjectMilk
dc.subjectQTL
dc.subjectRNA
dc.subjectRNA splicing
dc.subjectTranscriptomics
dc.subjectAnimals
dc.subjectCattle
dc.subjectDiacylglycerol O-Acyltransferase
dc.subjectExons
dc.subjectFemale
dc.subjectGene Expression
dc.subjectLactation
dc.subjectMilk
dc.subjectMutation
dc.titleA new mechanism for a familiar mutation - bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement
dc.typeJournal article
pubs.elements-id434282
pubs.organisational-groupOther
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