Longitudinal phenotypes improve genotype association for hyperketonemia in dairy cattle

Francisco A. Leal Yepes; Daryl V. Nydam; Sabine Mann; Luciano Caixeta; Jessica A.A. McArt; Thomas R. Overton; Joseph J. Wakshlag; Heather J. Huson

doi:10.3390/ani9121059

Longitudinal phenotypes improve genotype association for hyperketonemia in dairy cattle

Francisco A. Leal Yepes, Daryl V. Nydam, Sabine Mann, Luciano Caixeta, Jessica A.A. McArt, Thomas R. Overton, Joseph J. Wakshlag, Heather J. Huson

Veterinary Population Medicine

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5 Scopus citations

Abstract

The objective of our study was to identify genomic regions associated with varying concentrations of non-esterified fatty acid (NEFA), β-hydroxybutyrate (BHB), and the development of hyperketonemia (HYK) in longitudinally sampled Holstein dairy cows. Our study population consisted of 147 multiparous cows intensively characterized by serial NEFA and BHB concentrations. To identify individuals with contrasting combinations in longitudinal BHB and NEFA concentrations, phenotypes were established using incremental area under the curve (AUC) and categorized as follows: Group (1) high NEFA and high BHB, group (2) low NEFA and high BHB), group (3) low NEFA and low BHB, and group (4) high NEFA and low BHB. Cows were genotyped on the Illumina Bovine High-density (777K) beadchip. Genome-wide association studies using mixed linear models with the least-related animals were performed to establish a genetic association with HYK, BHB-AUC, NEFA-AUC, and the comparisons of the 4 AUC phenotypic groups using Golden Helix software. Nine single-nucleotide polymorphisms were associated with high longitudinal concentrations of BHB and further investigated. Five candidate genes related to energy metabolism and homeostasis were identified. These results provide biological insight and help identify susceptible animals thus improving genetic selection criteria thereby decreasing the incidence of HYK.

Original language	English (US)
Article number	1059
Journal	Animals
Volume	9
Issue number	12
DOIs	https://doi.org/10.3390/ani9121059
State	Published - Dec 2019

Bibliographical note

Funding Information:
Author Contributions: D.V.N.; T.R.O.; H.J.H.; and J.J.W. helped with conceptualization, acquired the funding, and administrated the project. J.A.A.M.-A.; S.M.; L.C.; and F.L.Y. performed investigation associated with this study. F.L.Y.; H.J.H.; S.M.; and J.A.A.M.-A. performed statistical analysis and F.L.Y. prepared manuscript. All authors reviewed and edited the manuscript upon submission Funding: This research was funded in part by NIFA, the Agriculture and Food Research Initiative competitive grant no. 2012–67015–30230 from the USDA National Institute of Food and Agriculture (Washington, D.C).

Publisher Copyright:
© 2019 by the authors Licensee MDPI, Basel, Switzerland.

Keywords

BHB
Dairy cow
GWAS
Hyperketonemia
Longitudinal phenotype
NEFA

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title = "Longitudinal phenotypes improve genotype association for hyperketonemia in dairy cattle",

abstract = "The objective of our study was to identify genomic regions associated with varying concentrations of non-esterified fatty acid (NEFA), β-hydroxybutyrate (BHB), and the development of hyperketonemia (HYK) in longitudinally sampled Holstein dairy cows. Our study population consisted of 147 multiparous cows intensively characterized by serial NEFA and BHB concentrations. To identify individuals with contrasting combinations in longitudinal BHB and NEFA concentrations, phenotypes were established using incremental area under the curve (AUC) and categorized as follows: Group (1) high NEFA and high BHB, group (2) low NEFA and high BHB), group (3) low NEFA and low BHB, and group (4) high NEFA and low BHB. Cows were genotyped on the Illumina Bovine High-density (777K) beadchip. Genome-wide association studies using mixed linear models with the least-related animals were performed to establish a genetic association with HYK, BHB-AUC, NEFA-AUC, and the comparisons of the 4 AUC phenotypic groups using Golden Helix software. Nine single-nucleotide polymorphisms were associated with high longitudinal concentrations of BHB and further investigated. Five candidate genes related to energy metabolism and homeostasis were identified. These results provide biological insight and help identify susceptible animals thus improving genetic selection criteria thereby decreasing the incidence of HYK.",

keywords = "BHB, Dairy cow, GWAS, Hyperketonemia, Longitudinal phenotype, NEFA",

author = "{Leal Yepes}, {Francisco A.} and Nydam, {Daryl V.} and Sabine Mann and Luciano Caixeta and McArt, {Jessica A.A.} and Overton, {Thomas R.} and Wakshlag, {Joseph J.} and Huson, {Heather J.}",

note = "Funding Information: Author Contributions: D.V.N.; T.R.O.; H.J.H.; and J.J.W. helped with conceptualization, acquired the funding, and administrated the project. J.A.A.M.-A.; S.M.; L.C.; and F.L.Y. performed investigation associated with this study. F.L.Y.; H.J.H.; S.M.; and J.A.A.M.-A. performed statistical analysis and F.L.Y. prepared manuscript. All authors reviewed and edited the manuscript upon submission Funding: This research was funded in part by NIFA, the Agriculture and Food Research Initiative competitive grant no. 2012–67015–30230 from the USDA National Institute of Food and Agriculture (Washington, D.C). Publisher Copyright: {\textcopyright} 2019 by the authors Licensee MDPI, Basel, Switzerland.",

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Longitudinal phenotypes improve genotype association for hyperketonemia in dairy cattle

Abstract

Bibliographical note

Keywords

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