A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle

Abstract Milk protein percentage (PP) and fat percentage (FP) are important indicators for measuring milk quality, but only a few causative genes such as DGAT1, GHR, and ABCG2, have been identified, indicating substantial potential for further exploration. Here, we integrated genotyping, RNA-seq, AT...

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Main Authors: Weijie Zheng, Junnan Zhang, Jinfeng Huang, Bo Han, Yanan Liu, Dongxiao Sun
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08615-6
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author Weijie Zheng
Junnan Zhang
Jinfeng Huang
Bo Han
Yanan Liu
Dongxiao Sun
author_facet Weijie Zheng
Junnan Zhang
Jinfeng Huang
Bo Han
Yanan Liu
Dongxiao Sun
author_sort Weijie Zheng
collection DOAJ
description Abstract Milk protein percentage (PP) and fat percentage (FP) are important indicators for measuring milk quality, but only a few causative genes such as DGAT1, GHR, and ABCG2, have been identified, indicating substantial potential for further exploration. Here, we integrated genotyping, RNA-seq, ATAC-seq, single-cell atlas and cis-QTLs datasets from the liver and mammary gland to investigate their genetic regulation. We identified cell type affecting milk composition, such as HPE2 and LumSec-HSPH1, and highlighted nine candidate genes (EFNA1, ERBB3, DUSP16, DEPTOR, TRIM46, HSTN, CIDEA, ACACA and SPP1) that are involved in the regulation of milk protein and fat synthesis through MAPK, AMPK, PI3K-Akt, and mTOR signalling pathways. Notably, EFNA1 was consistently identified across all omics analyses, showing increased promoter accessibility in the high PP group, potentially driven by CTCF and RXRA-mediated transcriptional activation. Overall, this study reveals potential cell types, candidate genes, and regulatory mechanisms influencing milk composition, offering insights to support milk quality improvement. The limited sample size represents the main constraint of this work, and future efforts will focus on population-scale genetic analyses and wet-lab validation.
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institution Kabale University
issn 2399-3642
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publishDate 2025-08-01
publisher Nature Portfolio
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spelling doaj-art-06cd351a5ef044158b9523511693e3212025-08-20T04:03:06ZengNature PortfolioCommunications Biology2399-36422025-08-018111410.1038/s42003-025-08615-6A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattleWeijie Zheng0Junnan Zhang1Jinfeng Huang2Bo Han3Yanan Liu4Dongxiao Sun5Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, State Key Laboratory of Animal Biotech Breeding, China Agricultural UniversityDepartment of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, State Key Laboratory of Animal Biotech Breeding, China Agricultural UniversityDepartment of Agriculture and Rural Affairs of Guangdong ProvinceDepartment of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, State Key Laboratory of Animal Biotech Breeding, China Agricultural UniversityDepartment of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, State Key Laboratory of Animal Biotech Breeding, China Agricultural UniversityDepartment of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, State Key Laboratory of Animal Biotech Breeding, China Agricultural UniversityAbstract Milk protein percentage (PP) and fat percentage (FP) are important indicators for measuring milk quality, but only a few causative genes such as DGAT1, GHR, and ABCG2, have been identified, indicating substantial potential for further exploration. Here, we integrated genotyping, RNA-seq, ATAC-seq, single-cell atlas and cis-QTLs datasets from the liver and mammary gland to investigate their genetic regulation. We identified cell type affecting milk composition, such as HPE2 and LumSec-HSPH1, and highlighted nine candidate genes (EFNA1, ERBB3, DUSP16, DEPTOR, TRIM46, HSTN, CIDEA, ACACA and SPP1) that are involved in the regulation of milk protein and fat synthesis through MAPK, AMPK, PI3K-Akt, and mTOR signalling pathways. Notably, EFNA1 was consistently identified across all omics analyses, showing increased promoter accessibility in the high PP group, potentially driven by CTCF and RXRA-mediated transcriptional activation. Overall, this study reveals potential cell types, candidate genes, and regulatory mechanisms influencing milk composition, offering insights to support milk quality improvement. The limited sample size represents the main constraint of this work, and future efforts will focus on population-scale genetic analyses and wet-lab validation.https://doi.org/10.1038/s42003-025-08615-6
spellingShingle Weijie Zheng
Junnan Zhang
Jinfeng Huang
Bo Han
Yanan Liu
Dongxiao Sun
A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle
Communications Biology
title A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle
title_full A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle
title_fullStr A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle
title_full_unstemmed A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle
title_short A pilot multi-omics study reveals genetic mechanisms regulating milk component traits in dairy cattle
title_sort pilot multi omics study reveals genetic mechanisms regulating milk component traits in dairy cattle
url https://doi.org/10.1038/s42003-025-08615-6
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