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Comparison of the transcriptome in circulating leukocytes in early lactation between primiparous and multiparous cows provides evidence for age-related changes

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  • Laura Buggiotti, Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom, United Kingdom
  • Zhangrui Cheng, Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom, United Kingdom
  • Mazdak Salavati, Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom, University of Edinburgh, United Kingdom
  • D. Claire Wathes, Royal Veterinary College, Hatfield, AL9 7TA, United Kingdom, United Kingdom
  • GplusE Consortium, Genotype Plus Environment Consortium (www.gpluse.eu)
Background: Previous studies have identified many immune pathways which are consistently altered in humans and model organisms as they age. Dairy cows are often culled at quite young ages due to an inability to cope adequately with metabolic and infectious diseases, resulting in reduced milk production and infertility. Improved longevity is therefore a desirable trait which would benefit both farmers and their cows. This study analysed the transcriptome derived from RNA-seq data of leukocytes obtained from Holstein cows in early lactation with respect to lactation number.

Results: Samples were divided into three lactation groups for analysis: i) primiparous (PP, n = 53), ii) multiparous inlactations 2–3 (MP 2–3, n = 121), and iii) MP in lactations 4–7 (MP > 3, n = 55). Leukocyte expression was comparedbetween PP vs MP > 3 cows with MP 2–3 as background using DESeq2 followed by weighted gene co-expressionnetwork analysis (WGCNA). Seven modules were significantly correlated (r ≥0.25) to the trait lactation number.Genes from the modules which were more highly expressed in either the PP or MP > 3 cows were pooled, and thegene lists subjected to David functional annotation cluster analysis. The top three clusters from modules more highly expressed in the PP cows all involved regulation of gene transcription, particularly zinc fingers. Another cluster included genes encoding enzymes in the mitochondrial beta-oxidation pathway. Top clusters up-regulated in MP > 3 cows included the terms Glycolysis/Gluconeogenesis, C-type lectin, and Immunity. Differentially expressed candidate genes for ageing previously identified in the human blood transcriptome up-regulated in PP cows were mainly associated with T-cell function (CCR7, CD27, IL7R, CAMK4, CD28), mitochondrial ribosomal proteins (MRPS27, MRPS9, MRPS31), and DNA replication and repair (WRN). Those up-regulated in MP > 3 cows encoded immune defence proteins (LYZ, CTSZ, SREBF1, GRN, ANXA5,  ADARB1).
Conclusions: Genes and pathways associated with lactation number in cows were identified for the first time to date, and we found that many were comparable to those known to be associated with ageing in humans and model organisms. We also detected changes in energy utilization and immune responses in leukocytes from older cows.
Original languageEnglish
Article number693
JournalBMC Genomics
Pages (from-to)1-17
Number of pages17
Publication statusPublished - Dec 2021

    Research areas

  • Ageing, Leukocytes, Cow, Primiparous, Multiparous, Longevity

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