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A common regulatory haplotype doubles lactoferrin concentration in milk.

Authors :
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
Source :
Genetics, selection, evolution : GSE [Genet Sel Evol] 2024 Mar 28; Vol. 56 (1), pp. 22. Date of Electronic Publication: 2024 Mar 28.
Publication Year :
2024

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.<br />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.<br />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.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
1297-9686
Volume :
56
Issue :
1
Database :
MEDLINE
Journal :
Genetics, selection, evolution : GSE
Publication Type :
Academic Journal
Accession number :
38549172
Full Text :
https://doi.org/10.1186/s12711-024-00890-x