A common regulatory haplotype doubles lactoferrin concentration in milk.

Lopdell TJ; Trevarton AJ; Moody J; Prowse-Wilkins C; Knowles S; Tiplady K; Chamberlain AJ; Goddard ME; Spelman RJ; Lehnert K; Snell RG; Davis SR; Littlejohn MD

A common regulatory haplotype doubles lactoferrin concentration in milk.

dc.citation.issue	1
dc.citation.volume	56
dc.contributor.author	Lopdell TJ
dc.contributor.author	Trevarton AJ
dc.contributor.author	Moody J
dc.contributor.author	Prowse-Wilkins C
dc.contributor.author	Knowles S
dc.contributor.author	Tiplady K
dc.contributor.author	Chamberlain AJ
dc.contributor.author	Goddard ME
dc.contributor.author	Spelman RJ
dc.contributor.author	Lehnert K
dc.contributor.author	Snell RG
dc.contributor.author	Davis SR
dc.contributor.author	Littlejohn MD
dc.coverage.spatial	France
dc.date.accessioned	2024-11-18T01:48:07Z
dc.date.available	2024-11-18T01:48:07Z
dc.date.issued	2024-03-28
dc.description.abstract	BACKGROUND: Bovine lactoferrin (Lf) is an iron absorbing whey protein with antibacterial, antiviral, and antifungal activity. Lactoferrin is economically valuable and has an extremely variable concentration in milk, partly driven by environmental influences such as milking frequency, involution, or mastitis. A significant genetic influence has also been previously observed to regulate lactoferrin content in milk. Here, we conducted genetic mapping of lactoferrin protein concentration in conjunction with RNA-seq, ChIP-seq, and ATAC-seq data to pinpoint candidate causative variants that regulate lactoferrin concentrations in milk. RESULTS: We identified a highly-significant lactoferrin protein quantitative trait locus (pQTL), as well as a cis lactotransferrin (LTF) expression QTL (cis-eQTL) mapping to the LTF locus. Using ChIP-seq and ATAC-seq datasets representing lactating mammary tissue samples, we also report a number of regions where the openness of chromatin is under genetic influence. Several of these also show highly significant QTL with genetic signatures similar to those highlighted through pQTL and eQTL analysis. By performing correlation analysis between these QTL, we revealed an ATAC-seq peak in the putative promotor region of LTF, that highlights a set of 115 high-frequency variants that are potentially responsible for these effects. One of the 115 variants (rs110000337), which maps within the ATAC-seq peak, was predicted to alter binding sites of transcription factors known to be involved in lactation-related pathways. CONCLUSIONS: Here, we report a regulatory haplotype of 115 variants with conspicuously large impacts on milk lactoferrin concentration. These findings could enable the selection of animals for high-producing specialist herds.
dc.description.confidential	false
dc.format.pagination	22-
dc.identifier.author-url	https://www.ncbi.nlm.nih.gov/pubmed/38549172
dc.identifier.citation	Lopdell TJ, Trevarton AJ, Moody J, Prowse-Wilkins C, Knowles S, Tiplady K, Chamberlain AJ, Goddard ME, Spelman RJ, Lehnert K, Snell RG, Davis SR, Littlejohn MD. (2024). A common regulatory haplotype doubles lactoferrin concentration in milk.. Genet Sel Evol. 56. 1. (pp. 22-).
dc.identifier.doi	10.1186/s12711-024-00890-x
dc.identifier.eissn	1297-9686
dc.identifier.elements-type	journal-article
dc.identifier.issn	0999-193X
dc.identifier.number	22
dc.identifier.pii	10.1186/s12711-024-00890-x
dc.identifier.uri	https://mro.massey.ac.nz/handle/10179/72015
dc.language	eng
dc.publisher	BioMed Central Ltd
dc.publisher.uri	http://gsejournal.biomedcentral.com/articles/10.1186/s12711-024-00890-x#Sec26
dc.relation.isPartOf	Genet Sel Evol
dc.rights	(c) 2024 The Author/s
dc.rights	CC BY 4.0
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Animals
dc.subject	Female
dc.subject	Haplotypes
dc.subject	Lactation
dc.subject	Lactoferrin
dc.subject	Milk
dc.subject	Cattle
dc.title	A common regulatory haplotype doubles lactoferrin concentration in milk.
dc.type	Journal article
pubs.elements-id	488061
pubs.organisational-group	College of Health