Dataset Information

Genome-wide association analysis for ?-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 ?-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.

SUBMITTER: Nayeri S

PROVIDER: S-EPMC6636026 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Nayeri S S Schenkel F F Fleming A A Kroezen V V Sargolzaei M M Baes C C Cánovas A A Squires J J Miglior F F

BMC genetics 20190716 1

<h4>Background</h4>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, ...[more]

PMID: 31311492

Similar Datasets

Project description:Sole ulcers (SUs) and white line disease (WLD) are two common noninfectious claw lesions (NICL) that arise due to a compromised horn production and are frequent causes of lameness in dairy cattle, imposing welfare and profitability concerns. Low to moderate heritability estimates of SU and WLD susceptibility indicate that genetic selection could reduce their prevalence. To identify the susceptibility loci for SU, WLD, SU and/or WLD, and any type of noninfectious claw lesion, genome-wide association studies (GWAS) were performed using generalized linear mixed model (GLMM) regression, chunk-based association testing (CBAT), and a random forest (RF) approach. Cows from five commercial dairies in California were classified as controls having no lameness records and ≥6 years old (n = 102) or cases having SU (n = 152), WLD (n = 117), SU and/or WLD (SU + WLD, n = 198), or any type of noninfectious claw lesion (n = 217). The top single nucleotide polymorphisms (SNPs) were defined as those passing the Bonferroni-corrected suggestive and significance thresholds in the GLMM analysis or those that a validated RF model considered important. Effects of the top SNPs were quantified using Bayesian estimation. Linkage disequilibrium (LD) blocks defined by the top SNPs were explored for candidate genes and previously identified, functionally relevant quantitative trait loci. The GLMM and CBAT approaches revealed the same regions of association on BTA8 for SU and BTA13 common to WLD, SU + WLD, and NICL. These SNPs had effects significantly different from zero, and the LD blocks they defined explained a significant amount of phenotypic variance for each dataset (6.1-8.1%, p < 0.05), indicating the small but notable contribution of these regions to susceptibility. These regions contained candidate genes involved in wound healing, skin lesions, bone growth and mineralization, adipose tissue, and keratinization. The LD block defined by the most significant SNP on BTA8 for SU included a SNP previously associated with SU. The RF models were overfitted, indicating that the SNP effects were very small, thereby preventing meaningful interpretation of SNPs and any downstream analyses. These findings suggested that variants associated with various physiological systems may contribute to susceptibility for NICL, demonstrating the complexity of genetic predisposition.

Project description:Sole ulcers (SU) and white line disease (WLD) are noninfectious claw lesions that arise due to compromised horn production and are common causes of lameness in dairy cattle, imposing welfare and profitability concerns. The low to moderate heritability estimates of SU and WLD susceptibility indicate that genetic selection could reduce their prevalence. To identify loci associated with SU and WLD susceptibility, generalized linear mixed model (GLMM) regression and random forest (RF) genome-wide association studies (GWAS) were performed. Cows from five commercial dairies in California were classified as sound controls having no instances of lameness and above six years of age (n = 102) or cases having SU (n = 152), WLD (n = 117), SU and/or WLD (SU+WLD, n = 198), or any type of noninfectious claw lesion (n = 217). Top SNPs were defined as those passing Bonferroni-corrected suggestive and significance thresholds in the GLMM analysis or those that a validated RF model considered important. Effects of top SNPs were quantified using Bayesian estimation. Linkage disequilibrium (LD) blocks defined by top SNPs were explored for candidate genes and previously identified, functionally relevant quantitative trait loci. The GLMM GWAS revealed regions of association on BTA8 for SU and BTA13 common to WLD, SU+WLD, and noninfectious claw lesions. Bayesian estimation of effect sizes indicated that these SNPs had effects significantly different from zero, indicating their small but notable contribution to susceptibility. Promising candidate genes identified in these regions were involved in wound healing, skin lesions, bone growth and mineralization, adipose tissue, and keratinization. The LD block defined by the most significant SNP on BTA8 for SU included a SNP previously reported to be associated with SU. The RF models were overfitted, indicating that SNP effects were very small and thereby preventing meaningful interpretation of SNPs with the highest importance values and downstream analyses. These findings suggested that variants associated with a variety of physiological systems may contribute to susceptibility for noninfectious claw lesions, demonstrating the complexity of genetic predisposition.

Project description:BACKGROUND: Breeding for enhanced immune response (IR) has been suggested as a tool to improve inherent animal health. Dairy cows with superior antibody-mediated (AMIR) and cell-mediated immune responses (CMIR) have been demonstrated to have a lower occurrence of many diseases including mastitis. Adaptive immune response traits are heritable, and it is, therefore, possible to breed for improved IR, decreasing the occurrence of disease. The objective of this study was to perform genome-wide association studies to determine differences in genetic profiles among Holstein cows classified as High or Low for AMIR and CMIR. From a total of 680 cows with immune response phenotypes, 163 cows for AMIR (81 High and 82 Low) and 140 for CMIR (75 High and 65 Low) were selectively genotyped using the Illumina Bovine SNP50 BeadChip. Results were validated using an unrelated population of 164 Holstein bulls IR phenotyped for AMIR and 146 for CMIR. RESULTS: A generalized quasi likelihood score method was used to determine single nucleotide polymorphisms (SNP) and chromosomal regions associated with immune response. After applying a 5% chromosomal false discovery rate, 186 SNPs were significantly associated with AMIR. The majority (93%) of significant markers were on chromosome 23, with a similar peak found in the bull population. For CMIR, 21 SNP markers remained significant. Candidate genes within 250,000 base pairs of significant SNPs were identified to determine biological pathways associated with AMIR and CMIR. Various pathways were identified, including the antigen processing and presentation pathway, important in host defense. Candidate genes included those within the bovine Major Histocompatability Complex such as BoLA-DQ, BoLA-DR and the non-classical BoLA-NC1 for AMIR and BoLA-DQ for CMIR, the complement system including C2 and C4 for AMIR and C1q for CMIR, and cytokines including IL-17A, IL17F for AMIR and IL-17RA for CMIR and tumor necrosis factor for both AMIR and CMIR. Additional genes associated with CMIR included galectins 1, 2 and 3, BCL2 and ?-defensin. CONCLUSIONS: The significant genetic variation associated with AMIR and CMIR in this study may imply feasibility to include immune response in genomic breeding indices as an approach to improve inherent animal health.

Project description:BACKGROUND: Contemporary dairy breeding goals have broadened to include, along with milk production traits, a number of non-production-related traits in an effort to improve the overall functionality of the dairy cow. Increased indirect selection for resistance to mastitis, one of the most important production-related diseases in the dairy sector, via selection for reduced somatic cell count has been part of these broadened goals. A number of genome-wide association studies have identified genetic variants associated with milk production traits and mastitis resistance, however the majority of these studies have been based on animals which were predominantly kept in confinement and fed a concentrate-based diet (i.e. high-input production systems). This genome-wide association study aims to detect associations using genotypic and phenotypic data from Irish Holstein-Friesian cattle fed predominantly grazed grass in a pasture-based production system (low-input). RESULTS: Significant associations were detected for milk yield, fat yield, protein yield, fat percentage, protein percentage and somatic cell score using separate single-locus, frequentist and multi-locus, Bayesian approaches. These associations were detected using two separate populations of Holstein-Friesian sires and cows. In total, 1,529 and 37 associations were detected in the sires using a single SNP regression and a Bayesian method, respectively. There were 103 associations in common between the sires and cows across all the traits. As well as detecting associations within known QTL regions, a number of novel associations were detected; the most notable of these was a region of chromosome 13 associated with milk yield in the population of Holstein-Friesian sires. CONCLUSIONS: A total of 276 of novel SNPs were detected in the sires using a single SNP regression approach. Although obvious candidate genes may not be initially forthcoming, this study provides a preliminary framework upon which to identify the causal mechanisms underlying the various milk production traits and somatic cell score. Consequently this will deepen our understanding of how these traits are expressed.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets