Genetic markers that influence feed efficiency phenotypes also affect cattle temperament as measured by flight speed

Flight speed is a predictive indicator of cattle temperament and is associated with feed efficiency phenotypes. Genetic markers associated with both traits may assist with selection of calmer animals with improved economic value. A preliminary genome‐wide association study determined chromosomal regions on BTA9, and 17 were associated with flight speed. The genes quaking (QKI), glutamate receptor, ionotropic, AMPA 2 (GRIA2) and glycine receptor β (GLRB) were identified in these regions as potential functional candidates. Beef steers (n = 1057) were genotyped with SNPs located within and flanking these genes. One SNP located near QKI and one near GRIA2 were nominally associated with flight speed (P ≤ 0.05) although neither was significant after Bonferroni correction. Several studies have shown a correlation between flight speed and feed intake or gain; therefore, we also analyzed SNPs on BTA6:38–39 Mb known to be associated with average daily gain (ADG) and average daily feed intake (ADFI) for association with flight speed. Several SNPs on BTA6 were associated with flight speed (P ≤ 0.005), and three were significant after Bonferroni correction. These results suggest that the genes tested are unlikely to contribute to flight speed variation for our cattle population, but SNPs on BTA6 associated with ADG and ADFI may influence temperament. Use of these markers to select for economically important feed efficiency phenotypes may produce cattle with more desirable temperaments.     

Genetic markers on BTA14 predictive for residual feed intake in beef steers and their effects on carcass and meat quality traits

With the high cost of feed for animal production, genetic selection for animals that metabolize feed more efficiently could result in substantial cost savings for cattle producers. The purpose of this study was to identify DNA markers predictive for differences among cattle for traits associated with feed efficiency. Crossbred steers were fed a high‐corn diet for 140 days and average daily feed intake (ADFI), average daily gain (ADG), and residual feed intake (RFI) phenotypes were obtained. A region on chromosome 14 was previously associated with RFI in this population of animals. To develop markers with the highest utility for predicting an animal's genetic potential for RFI, we genotyped additional markers within this chromosomal region. These polymorphisms were genotyped on the same animals (n = 1066) and tested for association with ADFI, ADG and RFI. Six markers within this region were associated with RFI (P ≤ 0.05). After conservative correction for multiple testing, one marker at 25.09 Mb remained significant (P = 0.02) and is responsible for 3.6% of the RFI phenotypic variation in this population of animals. Several of these markers were also significant for ADG, although none were significant after correction. Marker alleles with positive effects on ADG corresponded to lower RFI, suggesting an effect increasing growth without increasing feed intake. All markers were also assessed for their effects on meat quality and carcass traits. All of the markers associated with RFI were associated with adjusted fat thickness (AFT, P ≤ 0.009) and three were also associated with hot carcass weight (HCW, P ≤ 0.003). Marker alleles associated with lower RFI were also associated with reduced AFT, and if they were associated for HCW, the effect was an increase in weight. These markers may be useful as prediction tools for animals that utilize feed more efficiently; however, validation with additional populations of cattle is required.     

A genome-wide association study for feed efficiency-related traits in a crossbred pig population

Feed efficiency (FE) is one of the most important traits in pig production. However, it is difficult and costly to measure it, limiting the collection of large amount of data for an accurate selection for better FE. Therefore, the identification of single-nucleotide polymorphisms (SNPs) associated with FE-related traits to be used in the genetic evaluation is of great interest of pig breeding programs for increasing the prediction accuracy and the genetic progress of these traits. The objective of this study was to identify SNPs significantly associated with FE-related traits: average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR). We also aimed to identify potential candidate genes for these traits. Phenotypic information recorded on a population of 2386 three-way crossbreed pigs that were genotyped for 51 468 SNPs was used. We identified three loci of quantitative trait (QTL) regions associated with ADG and three QTL regions associated with ADFI; however, no significant association was found for FCR. A false discovery rate (FDR) ≤ 0.005 was used as the threshold for declaring an association as significant. The QTL regions associated with ADG on Sus scrofa chromosome (SSC) 1 were located between 177.01 and 185.47 Mb, which overlaps with the QTL regions for ADFI on SSC1 (173.26 and 185.47 Mb). The other QTL region for ADG was located on SSC12 (2.87 and 3.22 Mb). The most significant SNPs in these QTL regions explained up to 3.26% of the phenotypic variance of these traits. The non-identification of genomic regions associated with FCR can be explained by the complexity of this trait, which is a ratio between ADG and ADFI. Finally, the genes CDH19, CDH7, RNF152, MC4R, PMAIP1, FEM1B and GAA were the candidate genes found in the 1 Mb window around the QTL regions identified in this study. Among them, the MC4R gene (SSC1) has a well-known function related to ADG and ADFI. In this study, we identified three QTL regions for ADG (SSC1 and SSC12) and three for ADFI (SSC1). These regions were previously described in purebred pig populations; however, to our knowledge, this is the first study to confirm the relevance of these QTL regions in a crossbred pig population. The potential use of the SNPs and genes identified in this study in prediction models that combine genomic selection and marker-assisted selection should be evaluated for increasing the prediction accuracy of these traits in this population.     

Whole Genome Association Studies of Residual Feed Intake and Related Traits in the Pig

Background

Residual feed intake (RFI), a measure of feed efficiency, is the difference between observed feed intake and the expected feed requirement predicted from growth and maintenance. Pigs with low RFI have reduced feed costs without compromising their growth. Identification of genes or genetic markers associated with RFI will be useful for marker-assisted selection at an early age of animals with improved feed efficiency.

Methodology/Principal findings

Whole genome association studies (WGAS) for RFI, average daily feed intake (ADFI), average daily gain (ADG), back fat (BF) and loin muscle area (LMA) were performed on 1,400 pigs from the divergently selected ISU-RFI lines, using the Illumina PorcineSNP60 BeadChip. Various statistical methods were applied to find SNPs and genomic regions associated with the traits, including a Bayesian approach using GenSel software, and frequentist approaches such as allele frequency differences between lines, single SNP and haplotype analyses using PLINK software. Single SNP and haplotype analyses showed no significant associations (except for LMA) after genomic control and FDR. Bayesian analyses found at least 2 associations for each trait at a false positive probability of 0.5. At generation 8, the RFI selection lines mainly differed in allele frequencies for SNPs near (<0.05 Mb) genes that regulate insulin release and leptin functions. The Bayesian approach identified associations of genomic regions containing insulin release genes (e.g., GLP1R, CDKAL, SGMS1) with RFI and ADFI, of regions with energy homeostasis (e.g., MC4R, PGM1, GPR81) and muscle growth related genes (e.g., TGFB1) with ADG, and of fat metabolism genes (e.g., ACOXL, AEBP1) with BF. Specifically, a very highly significantly associated QTL for LMA on SSC7 with skeletal myogenesis genes (e.g., KLHL31) was identified for subsequent fine mapping.

Conclusions/significance

Important genomic regions associated with RFI related traits were identified for future validation studies prior to their incorporation in marker-assisted selection programs.     

Bivariate Genome-Wide Association Analysis of the Growth and Intake Components of Feed Efficiency

Single nucleotide polymorphisms (SNPs) associated with average daily gain (ADG) and dry matter intake (DMI), two major components of feed efficiency in cattle, were identified in a genome-wide association study (GWAS). Uni- and multi-SNP models were used to describe feed efficiency in a training data set and the results were confirmed in a validation data set. Results from the univariate and bivariate analyses of ADG and DMI, adjusted by the feedlot beef steer maintenance requirements, were compared. The bivariate uni-SNP analysis identified (P-value <0.0001) 11 SNPs, meanwhile the univariate analyses of ADG and DMI identified 8 and 9 SNPs, respectively. Among the six SNPs confirmed in the validation data set, five SNPs were mapped to KDELC2, PHOX2A, and TMEM40. Findings from the uni-SNP models were used to develop highly accurate predictive multi-SNP models in the training data set. Despite the substantially smaller size of the validation data set, the training multi-SNP models had slightly lower predictive ability when applied to the validation data set. Six Gene Ontology molecular functions related to ion transport activity were enriched (P-value <0.001) among the genes associated with the detected SNPs. The findings from this study demonstrate the complementary value of the uni- and multi-SNP models, and univariate and bivariate GWAS analyses. The identified SNPs can be used for genome-enabled improvement of feed efficiency in feedlot beef cattle, and can aid in the design of empirical studies to further confirm the associations.     

Genome-wide association analysis for feed efficiency in Angus cattle

Estimated breeding values for average daily feed intake (AFI; kg/day), residual feed intake (RFI; kg/day) and average daily gain (ADG; kg/day) were generated using a mixed linear model incorporating genomic relationships for 698 Angus steers genotyped with the Illumina BovineSNP50 assay. Association analyses of estimated breeding values (EBVs) were performed for 41,028 single nucleotide polymorphisms (SNPs), and permutation analysis was used to empirically establish the genome-wide significance threshold (P < 0.05) for each trait. SNPs significantly associated with each trait were used in a forward selection algorithm to identify genomic regions putatively harbouring genes with effects on each trait. A total of 53, 66 and 68 SNPs explained 54.12% (24.10%), 62.69% (29.85%) and 55.13% (26.54%) of the additive genetic variation (when accounting for the genomic relationships) in steer breeding values for AFI, RFI and ADG, respectively, within this population. Evaluation by pathway analysis revealed that many of these SNPs are in genomic regions that harbour genes with metabolic functions. The presence of genetic correlations between traits resulted in 13.2% of SNPs selected for AFI and 4.5% of SNPs selected for RFI also being selected for ADG in the analysis of breeding values. While our study identifies panels of SNPs significant for efficiency traits in our population, validation of all SNPs in independent populations will be necessary before commercialization.     

Expression of candidate genes for residual feed intake in Angus cattle

Residual feed intake (RFI) has been adopted in Australia for the purpose of genetic improvement in feed efficiency in beef cattle. RFI is the difference between the observed feed intake of an animal and the predicted feed intake based on its size and growth rate over a test period. Gene expression of eight candidate genes (AHSG, GHR, GSTM1, INHBA, PCDH19, S100A10, SERPINI2 and SOD3), previously identified as differentially expressed between divergent lines of high‐ and low‐RFI animals, was measured in an unselected population of 60 steers from the Angus Society Elite Progeny Test Program using quantitative real‐time PCR. Results showed that the levels of gene expression were significantly correlated with RFI. The genes explain around 33.2% of the phenotypic variance in RFI, and prediction equations using the expression data are reasonably accurate estimators of RFI. The association of these genes with economically important traits, such as other feed efficiency‐related traits and fat, growth and carcass traits, was investigated as well. The expression of these candidate genes was significantly correlated with feed conversion ratio and daily feed intake, which are highly associated with RFI, suggesting a functional role for these genes in modulating feed utilisation. The expression of these genes did not show any association with average daily gain, eye muscle area and carcass composition.     

Genome-Wide Association Study Reveals Genetic Architecture of Eating Behavior in Pigs and Its Implications for Humans Obesity by Comparative Mapping

This study was aimed at identifying genomic regions controlling feeding behavior in Danish Duroc boars and its potential implications for eating behavior in humans. Data regarding individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of daily visits to feeder (NVD), average duration of each visit (TPV), mean feed intake per visit (FPV) and mean feed intake rate (FR) were available for 1130 boars. All boars were genotyped using the Illumina Porcine SNP60 BeadChip. The association analyses were performed using the GenABEL package in the R program. Sixteen SNPs were found to have moderate genome-wide significance (p<5E-05) and 76 SNPs had suggestive (p<5E-04) association with feeding behavior traits. MSI2 gene on chromosome (SSC) 14 was very strongly associated with NVD. Thirty-six SNPs were located in genome regions where QTLs have previously been reported for behavior and/or feed intake traits in pigs. The regions: 64–65 Mb on SSC 1, 124–130 Mb on SSC 8, 63–68 Mb on SSC 11, 32–39 Mb and 59–60 Mb on SSC 12 harbored several signifcant SNPs. Synapse genes (GABRR2, PPP1R9B, SYT1, GABRR1, CADPS2, DLGAP2 and GOPC), dephosphorylation genes (PPM1E, DAPP1, PTPN18, PTPRZ1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome. This is the first translational genomics study of its kind to report potential candidate genes for eating behavior in humans.     

Genome‐wide association study identifies loci linked to serum electrolyte traits in Chinese Holstein cattle

We aimed to identify QTL for serum electrolyte traits by performing a GWAS of calcium, chloride, sodium, potassium and magnesium ion concentrations in Chinese Holstein cattle. We detected five SNPs that had significant associations with calcium ion concentrations and identified GATA2 from Bos taurus chromosome (BTA)22 as having the highest significance. Among the genes with significant results, we speculate that TMEM123 might be related to calcium channel proteins according to the functions of the TMEM family.     

Quantitative trait loci mapping for conjugated linoleic acid,vaccenic acid and ∆9‐desaturase in Italian Brown Swiss dairy cattle using selective DNA pooling

A selective DNA pooling approach was applied to identify QTL for conjugated linoleic acid (CLA), vaccenic acid (VA) and Δ⁹‐desaturase (D9D) milk content in Italian Brown Swiss dairy cattle. Milk samples from 60 animals with higher values (after correction for environmental factors) and 60 animals with lower values for each of these traits from each of five half‐sib families were pooled separately. The pools were genotyped using the Illumina BovineSNP50 BeadChip. Sire allele frequencies were compared between high and low tails at the sire and marker level for SNPs for which the sires were heterozygous. An r procedure was implemented to perform data analysis in a selective DNA pooling design. A correction for multiple tests was applied using the proportion of false positives among all test results. BTA 19 showed the largest number of markers in association with CLA. Associations between SNPs and the VA and Δ⁹‐desaturase traits were found on several chromosomes. A bioinformatics survey identified genes with an important role in pathways for milk fat and fatty acids metabolism within 1 Mb of SNP markers associated with fatty acids contents.     

A genome‐wide association analysis for carcass traits in a commercial Duroc pig population

We performed a genome‐wide association study to map the genetic determinants of carcass traits in 350 Duroc pigs typed with the Porcine SNP60 BeadChip. Association analyses were carried out using the gemma software. The proportion of phenotypic variance explained by the SNPs ranged between negligible to moderate (= 0.01–0.30) depending on the trait under consideration. At the genome‐wide level, we detected one significant association between backfat thickness between the 3^rd and 4^th ribs and six SNPs mapping to SSC12 (37–40 Mb). We also identified several chromosome‐wide significant associations for ham weight (SSC11: 51–53 Mb, three SNPs; 67–68 Mb, two SNPs), carcass weight (SSC11: 66–68 Mb, two SNPs), backfat thickness between the 3^rd and 4^th ribs (SSC12: 21 Mb, one SNP; 33–40 Mb, 17 SNPs; 51–58 Mb, two SNPs), backfat thickness in the last rib (SSC12: 37 Mb, one SNP; 40–41 Mb, nine SNPs) and lean meat content (SSC13: 34 Mb, three SNPs and SSC16: 45.1 Mb, one SNP; 62–63 Mb, 10 SNPs; 71–75 Mb, nine SNPs). The ham weight trait‐associated region on SSC11 contains two genes (UCHL3 and LMO7) related to muscle development. In addition, the ACACA gene, which encodes an enzyme for the catalysis of fatty acid synthesis, maps to the SSC12 (37–41 Mb) region harbouring trait‐associated regions for backfat thickness traits. Sequencing of these candidate genes may help to uncover the causal mutations responsible for the associations found in the present study.     

A catalogue of validated single nucleotide polymorphisms in bovine orthologs of mammalian imprinted genes and associations with beef production traits

Genetic (or ‘genomic’) imprinting, a feature of approximately 100 mammalian genes, results in monoallelic expression from one of the two parentally inherited chromosomes. To date, most studies have been directed on imprinted genes in murine or human models; however, there is burgeoning interest in the effects of imprinted genes in domestic livestock species. In particular, attention has focused on imprinted genes that influence foetal growth and development and that are associated with several economically important production traits in cattle, sheep and pigs. We have re-sequenced regions in 20 candidate bovine imprinted genes in order to validate single nucleotide polymorphisms (SNPs) that may influence important production traits in cattle. Putative SNPs detected via re-sequencing were subsequently re-formatted for high-throughput SNP genotyping in 185 cattle samples comprising 138 performance-tested European Bos taurus (all Limousin bulls), 29 African B. taurus and 18 Indian B. indicus samples. Analysis of the resulting genotypic data identified 117 validated SNPs. Preliminary genotype–phenotype association analyses using 83 SNPs that were polymorphic in the Limousin samples with minor allele frequencies ⩾0.05 revealed significant associations between two candidate bovine imprinted genes and a range of important beef production traits: average daily gain, average feed intake, live weight, feed conversion ratio, residual feed intake and residual gain. These genes were the Ras protein-specific guanine nucleotide releasing factor gene (RASGRF1) and the zinc finger, imprinted 2 gene (ZIM2). Despite the relatively small sample size used in these analyses, the observed associations with production traits are supported by the purported biological function of the RASGRF1 and ZIM2 gene products. These results support the hypothesis that imprinted genes contribute significantly to important complex production traits in cattle. Furthermore, these SNPs may be usefully incorporated into future marker-assisted and genomic selection breeding schemes.     

Genome-wide association study identifies loci and candidate genes for meat quality traits in Simmental beef cattle

Improving meat quality is the best way to enhance profitability and strengthen competitiveness in beef industry. Identification of genetic variants that control beef quality traits can help breeders design optimal breeding programs to achieve this goal. We carried out a genome-wide association study for meat quality traits in 1141 Simmental cattle using the Illumina Bovine HD 770K SNP array to identify the candidate genes and genomic regions associated with meat quality traits for beef cattle, including fat color, meat color, marbling score, longissimus muscle area, and shear force. In our study, we identified twenty significant single-nucleotide polymorphisms (SNPs) (p < 1.47 × 10^?6) associated with these five meat quality traits. Notably, we observed several SNPs were in or near eleven genes which have been reported previously, including TMEM236, SORL1, TRDN, S100A10, AP2S1, KCTD16, LOC506594, DHX15, LAMA4, PREX1, and BRINP3. We identified a haplotype block on BTA13 containing five significant SNPs associated with fat color trait. We also found one of 19 SNPs was associated with multiple traits (shear force and longissimus muscle area) on BTA7. Our results offer valuable insights to further explore the potential mechanism of meat quality traits in Simmental beef cattle.     

Association of SCD1 and DGAT1 SNPs with the intramuscular fat traits in Chinese Simmental cattle and their distribution in eight Chinese cattle breeds

Intramuscular fat (IMF) is a key parameter for evaluation of nutritional quality of beef, with its endogenous synthesis regulated by stearoyl CoA desaturase (SCD1) and diacylglycerol-acyl transferase 1 (DGAT1) genes in cattle. The object of this research was to evaluate the effect of SCD1 and DGAT1 polymorphisms on IMF trait in beef cattle and to estimate the frequency distribution of SNPs in the two genes in Chinese cattle populations. The SCD1 and DGAT1 polymorphisms were detected by PCR-single strand conformation polymorphism (PCR-SSCP) method in Chinese Simmental cattle and their associations with IMF traits were analyzed using the general linear model (GLM). The frequency distribution of SNPs in SCD1 and DGAT1 genes were detected by PCR-SSCP method and analyzed in seven other cattle populations. The results showed significant associations of SNPs SCD1-878, SCD1-762, and DGAT1 10433 and 10434 with IMF (%) and shearing force values (SFV; kg) in Chinese Simmental cattle. A haplotype combining SCD1-878C, SCD1-762T, and DGAT1 10433 and 10434-GC had the highest IMF, marbling score and shearing force. The polymorphic investigation indicated that the frequency of SCD1-878C or SCD1-762T was significantly higher in Chinese southern cattle (Leiqiong, Yunnan High pump, BMY or Minnan Cattle) than in Chinese northern cattle (Chinese Simmental, Luxi Cattle, Bohai Black or Chinese Holstein), while the frequency of DGAT1 10433 and 10434-GC in Chinese indigenous breed (Leiqiong, Yunnan High pump, BMY, Luxi Cattle, Bohai Black, or Minnan Cattle) was significantly lower than breeds with imported blood (Chinese Simmental or Chinese Holstein). These findings demonstrated that both the SCD1 and DGAT1 SNPs were prospect genetic markers for IMF traits, and the SCD1 SNPs could be used as a genetic marker for southern or northern blood in Chinese cattle.