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Transcriptomic profiling of milk fat globules in cows with different β-casein genotypes.
L Jiménez-Montenegro1, L Alfonso1, B Soret1
1IS-FOOD, School of Agricultural Engineering and Biosciences, Public University of Navarre (UPNA), Campus de Arrosadia, 31006, Pamplona, Spain.
Scientific Reports
|September 29, 2025
Summary
The A2 β-casein genotype in cows shows minimal impact on mammary gland gene expression. This suggests current breeding strategies for A2A2 cows are not significantly altering milk synthesis at the transcriptomic level.
Area of Science:
- Dairy Science
- Genomics
- Molecular Biology
Background:
- Growing interest in A2 β-casein milk for potential health benefits.
- Selective breeding for A2A2 genotype cows is increasing globally.
- The impact of β-casein genotype on mammary gland gene expression is largely unknown.
Purpose of the Study:
- To investigate gene expression differences in the milk fat globule (MFG) transcriptome between A1A1 and A2A2 β-casein genotype cows.
- To determine if β-casein genotype influences milk synthesis or composition through transcriptomic changes.
- To provide insights for selective breeding strategies focused on A2A2 milk production.
Main Methods:
- RNA sequencing (RNA-seq) was performed on MFG from 14 cows with distinct β-casein genotypes (A1A1 vs. A2A2).
- Functional enrichment analysis identified key processes in MFG, including protein synthesis, milk fat secretion, and energy metabolism.
- Differential gene expression analysis was conducted using DESeq2 and EdgeR.
Main Results:
- Highly expressed transcripts in MFG included CSN1S1, PAEP/BLG, CSN2, GLYCAM1, COX1, COX3, and CSN3.
- Minimal gene-level differences were observed between A1A1 and A2A2 groups, with only two genes significantly altered.
- NADH dehydrogenase subunit 6 (ND6) and 16S mitochondrial rRNA (16S Mt-rRNA) were down-regulated in A2A2 cows, suggesting potential minor impacts on mitochondrial activity.
Conclusions:
- The β-casein genotype (A1A1 vs. A2A2) shows no strong association with significant gene-level transcriptomic differences in the bovine mammary gland.
- The findings support the current selective breeding strategies for A2A2 genotype cows.
- Further research into post-transcriptional regulatory mechanisms is recommended to fully understand genotype-phenotype relationships.

