Genetic and nongenetic profiling of milk β-hydroxybutyrate and acetone and their associations with ketosis in Holstein cows

Abstract

Ketosis is a metabolic disorder of increasing importance in high-yielding dairy cows, but accurate population-wide binary health trait recording is difficult to implement. Against this background, proper Gaussian indicator traits, which can be routinely measured in milk, are needed. Consequently, we focused on the ketone bodies acetone and β-hydroxybutyrate (BHB), measured via Fourier-transform infrared spectroscopy (FTIR) in milk. In the present study, 62,568 Holstein cows from large-scale German co-operator herds were phenotyped for clinical ketosis (KET) according to a veterinarian diagnosis key. A sub-sample of 16,861 cows additionally had first test-day observations for FTIR acetone and BHB. Associations between FTIR acetone and BHB with KET and with test-day traits were studied phenotypically and quantitative genetically. Furthermore, we estimated SNP marker effects for acetone and BHB (application of genome-wide association studies) based on 40,828 SNP markers from 4,384 genotyped cows, and studied potential candidate genes influencing body fat mobilization. Generalized linear mixed models were applied to infer the influence of binary KET on Gaussian-distributed acetone and BHB (definition of an identity link function), and vice versa, such as the influence of acetone and BHB on KET (definition of a logit link function). Additionally, linear models were applied to study associations between BHB, acetone and test-day traits (milk yield, fat percentage, protein percentage, fat-to-protein ratio and somatic cell score) from the first test-day after calving. An increasing KET incidence was statistically significant associated with increasing FTIR acetone and BHB milk concentrations. Acetone and BHB concentrations were positively associated with fat percentage, fat-toprotein ratio and somatic cell score. Bivariate linear animal models were applied to estimate genetic (co) variance components for KET, acetone, BHB and testday traits within parities 1 to 3, and considering all parities simultaneously in repeatability models. Pedigree-based heritabilities were quite small (i.e., in the range from 0.01 in parity 3 to 0.07 in parity 1 for acetone, and from 0.03-0.04 for BHB). Heritabilites from repeatability models were 0.05 for acetone, and 0.03 for BHB. Genetic correlations between acetone and BHB were moderate to large within parities and considering all parities simultaneously (0.69-0.98). Genetic correlations between acetone and BHB with KET from different parities ranged from 0.71 to 0.99. Genetic correlations between acetone across parities, and between BHB across parities, ranged from 0.55 to 0.66. Genetic correlations between KET, acetone, and BHB with fatto-protein ratio and with fat percentage were large and positive, but negative with milk yield. In genome-wide association studies, we identified SNP on BTA 4, 10, 11, and 29 significantly influencing acetone, and on BTA 1 and 16 significantly influencing BHB. The identified potential candidate genes NRXN3, ACOXL, BCL2L11, HIBADH, KCNJ1, and PRG4 are involv...

Genomewide Association Analyses of Lactation Persistency and Milk Production Traits in Holstein Cattle Based on Imputed Whole-Genome Sequence Data

“…After imputation to WGS, an additional QC was performed to remove the individuals and SNPs with a missing rate greater than 0.1, minor allele frequency (MAF) lower than 0.01, and extreme deviation from Hardy-Weinberg equilibrium (p < 10 −8 ; e.g., [41][42][43]. Finally, a range of 5,108,861 to 6,101,357 SNPs remained for the GWAS analyses of LP and milk production traits.…”

Investigation of β‐hydroxybutyrate in early lactation of Simmental cows: Genetic parameters and genomic predictions

“…( 2018 ) observed a repeatability of 0.20 for BHB, whereas Klein et al. ( 2020 ) reported values lower than 10% due to small PE variances (genomic‐based). Repeatability estimates closer to the ones in the present study were found in the literature for blood BHB: Benedet et al.…”

“…Luke et al (2019) reported genomic-based h 2 of 0.09 ± 0.04 for BHB LOG10 measured within 30 days after calving in 1,393 Holstein-Friesian Australian cows. Benedet et al (2018) observed a repeatability of 0.20 for BHB, whereas Klein et al (2020) reported values lower than 10% due to small PE variances (genomic-based). Repeatability estimates closer to the ones in the present study were found in the literature for blood BHB: Benedet et al (2020) reported r 2 of 0.26 ± 0.01 in early-lactation (up to 35 days in milk) Holstein cows (pedigree-based).…”

Genomic loci and genetic parameters for uterine diseases in first-parity Holstein cows and associations with milk production and fertility

“…The genome-wide significance level according to Bonferroni was 1.22 × 10 −6 (pBonf = 0.05/N SNP = 40,824). In addition, we considered a less conservative suggestive significance candidate threshold (pCand = 1 × 10 −4 ) according to Kurz et al (2019) and Klein et al (2020). Potential candidate genes were queried and assigned to the associated SNP using the ENSEMBL database based on the Bos taurus ARS-UCD1.2 genome assembly (Yates et al, 2020).…”