A common regulatory haplotype doubles lactoferrin concentration in milk - Genetics Selection Evolution Access content directly
Journal Articles Genetics Selection Evolution Year : 2024

A common regulatory haplotype doubles lactoferrin concentration in milk

Thomas J. Lopdell
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Janelle Moody
  • Function : Author
Claire Prowse-Wilkins
  • Function : Author
Sarah Knowles
  • Function : Author
Kathryn Tiplady
  • Function : Author
Amanda J. Chamberlain
  • Function : Author
Michael E. Goddard
  • Function : Author
Richard J. Spelman
  • Function : Author
Klaus Lehnert
  • Function : Author
Russell G. Snell
  • Function : Author
Stephen R. Davis
  • Function : Author
Mathew D. Littlejohn
  • Function : Author


AbstractBackgroundBovine 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.ResultsWe identified a highly-significant lactoferrin protein quantitative trait locus (pQTL), as well as a cislactotransferrin (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.ConclusionsHere, 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.
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Origin Publication funded by an institution
Origin Publication funded by an institution

Dates and versions

hal-04531070 , version 1 (03-04-2024)



Thomas J. Lopdell, Alexander J. Trevarton, Janelle Moody, Claire Prowse-Wilkins, Sarah Knowles, et al.. A common regulatory haplotype doubles lactoferrin concentration in milk. Genetics Selection Evolution, 2024, 56 (1), pp.22. ⟨10.1186/s12711-024-00890-x⟩. ⟨hal-04531070⟩
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