Genome-wide association analysis for β-hydroxybutyrate concentration in Milk in Holstein dairy cattle

Abstract

Background Ketosis in dairy cattle has been shown to cause a high morbidity in the farm and substantial financial losses to dairy farmers. Ketosis symptoms, however, are difficult to identify, therefore, the amount of ketone bodies (mainly β-hydroxybutyric acid, BHB) is used as an indicator of subclinical ketosis in cows. It has also been shown that milk BHB concentrations have a strong correlation with ketosis in dairy cattle. Mid-infrared spectroscopy (MIR) has recently became a fast, cheap and high-throughput method for analyzing milk components. The aim of this study was to perform a genome-wide association study (GWAS) on the MIR-predicted milk BHB to identify genomic regions, genes and pathways potentially affecting subclinical ketosis in North American Holstein dairy cattle. Results Several significant regions were identified associated with MIR-predicted milk BHB concentrations (indicator of subclinical ketosis) in the first lactation (SCK1) and second and later lactations (SCK2) in Holstein dairy cows. The strongest association was located on BTA6 for SCK1 and BTA14 on SCK2. Several SNPs on BTA6 were identified in regions and variants reported previously to be associated with susceptibility to ketosis and clinical mastitis in Jersey and Holstein dairy cattle, respectively. One highly significant SNP on BTA14 was found within the DGAT1 gene with known functions on fat metabolism and inflammatory response in dairy cattle. A region on BTA6 and three SNPs on BTA20 were found to overlap between SCK1 and SCK2. However, a novel region on BTA20 (55–63 Mb) for SCK2 was also identified, which was not reported in previous association studies. Enrichment analysis of the list of candidate genes within the identified regions for MIR-predicted milk BHB concentrations yielded molecular functions and biological processes that may be involved in the inflammatory response and lipid metabolism in dairy cattle. Conclusions The results of this study confirmed several SNPs and genes identified in previous studies as associated with ketosis susceptibility and immune response, and also found a novel region that can be used for further analysis to identify causal variations and key regulatory genes that affect clinical/ subclinical ketosis. Electronic supplementary material The online version of this article (10.1186/s12863-019-0761-9) contains supplementary material, which is available to authorized users.

Differential gene expression in dairy cows under negative energy balance and ketosis: A systematic review and meta-analysis

“…From the 430 significant SNPs obtained from published GWAS, 24 of them were located within 14 differentially expressed genes (Table 1). This set of 24 SNPs are located on chromosomes 2, 3, 6, 9, 11, 14, 27, and 29 and were selected from 3 different studies, which investigated milk levels of prognostic ketosis biomarkers (Tetens et al, 2015), candidate genes for ketosis resistance (Kroezen et al, 2018), and BHB concentration in milk (Nayeri et al, 2019) in dairy cattle.…”

“…The low heritability estimates for this trait may be due to the subjective nature of its diagnosis, since BHB, an indicator trait for ketosis, has a relatively higher heritability of 0.14 to 0.28 (van der Drift et al, 2012). To better understand this metabolic problem, several studies have investigated the biological processes, metabolic pathways, candidate genes, and gene networks that influence NEB and subclinical and clinical ketosis in dairy cows by performing gene expression and genome-wide association studies (GWAS;McCabe et al, 2012;Ha et al, 2015;Tetens et al, 2015;Huang et al, 2019;Nayeri et al, 2019). The relationship among patterns of gene expression that occur as the clinical condition progresses from NEB to ketosis could be better understood by connecting information of the main metabolic pathways associated with this process.…”

Breed Ancestry, Divergence, Admixture, and Selection Patterns of the Simbra Crossbreed

“…For example, the region located on BTA 3, which is known to be under selection in Western and Russian Simmental populations (Mészáros et al, 2019 ) and most likely derived from the Simmental parent breed, overlaps with a QTL associated with ketosis (QTL:179821). The latter is a metabolic disorder where negative energy balances (when energy demand exceeds intake) affect animal health and productivity (Nayeri et al, 2019 ). It has been postulated that such failure to maintain internal homeostatic and homeorhetic regulation maybe caused by intense genetic selection (Nayeri et al, 2019 ).…”

<strong>Detection of Whole Genome Selection Signatures of Pakistani Teddy Goat</strong>

“…and VPS13B related to lactation (Gao et al 2017;Nayeri et al 2019;Zhang et al 2019). The genetic architecture underlying body height trait in Teddy presents 8 candidate genes e.g.…”