A common regulatory haplotype doubles lactoferrin concentration in milk

Area of Science:

• Animal Genomics
• Dairy Science
• Proteomics

Background:

• Bovine lactoferrin (Lf) is an iron-binding whey protein with antimicrobial properties.
• Lf concentration in milk varies due to environmental factors and genetics.
• Understanding genetic regulation of Lf is crucial for dairy production.

Purpose of the Study:

• To identify genetic variants regulating bovine milk lactoferrin concentration.
• To pinpoint causative variants using multi-omics data integration.

Main Methods:

• Genetic mapping of lactoferrin protein quantitative trait loci (pQTL).
• RNA-sequencing (RNA-seq) for expression QTL (eQTL) analysis.
• Chromatin immunoprecipitation sequencing (ChIP-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq) on mammary tissue.
• Correlation analysis between QTL and variant identification.

Main Results:

• A significant pQTL and cis-eQTL were identified at the lactotransferrin (LTF) locus.
• ATAC-seq revealed genetically influenced chromatin accessibility near the LTF promoter.
• A haplotype of 115 variants, including rs110000337, was associated with significant changes in Lf concentration, potentially affecting transcription factor binding.

Conclusions:

• A regulatory haplotype significantly impacts bovine milk lactoferrin levels.
• These genetic insights can guide the selection of high-lactoferrin producing cattle for dairy herds.