Candidate genes and single nucleotide polymorphisms associated with variation in residual feed intake in beef cattle.

The candidate gene approach was used to identify genes associated with residual feed intake (RFI) in beef steers. The approach uses prior knowledge of gene functions to predict their biological role in the variation observed in a trait. It is suited to identify genes associated with complex traits where each gene has a relatively small effect. First, positional candidate genes were identified within the genomic positions of previously reported QTL associated with component traits related to RFI such as dry matter intake (DMI), growth, feed conversion ratio (FCR), average daily gain (ADG), and energy balance. Secondly, the positional candidate genes were prioritized into functional candidate genes according to their biological functions and their relationship with the biological processes associated with RFI including carbohydrate, fat and protein metabolism, thermoregulation, immunity and muscle activity. Single nucleotide polymorphisms (SNPs) located within the functional candidate genes were identified using mRNA sequences and prioritized into functional classes such as non-synonymous (nsSNP), synonymous (sSNP) or intronic SNP. A total of 117 nsSNP were considered as functional SNP and genotyped in steers at the University of Alberta ranch in Kinsella. Multiple marker association analysis in ASReml was performed using RFI data obtained from 531 beef steers. Twenty-five SNP were significantly associated with RFI (P < 0.05) accounting for 19.7% of the phenotypic variation. Using SIFT program to predict the effect of the SNP on the function of the corresponding protein, 3 of the 25 SNP were predicted to cause a significant effect on protein function (P < 0.05). One of the 3 SNP was located in the GHR gene and was also associated with a significant effect on the tertiary structure of the GHR protein (P < 0.05) as modeled using SWISSModel software. Least square means for each genotype were estimated and an over-dominance effect was observed for the SNP located in the GHR, CAST, ACAD11 and UGT3A1 genes. In addition, 2 other SNP showed a dominance effect and 3 genes had an additive effect. Gene network analysis performed in Ingenuity pathway analysis (IPA) software (Ingenuity Systems, www.ingenuity.com) indicated that the significant genes were involved in biological pathways such as lipid, protein and energy metabolism, electron transport and membrane signaling. The genes in this study, if validated in other beef cattle populations, may be useful for marker assisted selection for feed efficiency.

Karisa BK ，Thomson J ，Wang Z ，Stothard P ，Moore SS ，Plastow GS ... -  《-》

Identification of single nucleotide polymorphisms in genes involved in digestive and metabolic processes associated with feed efficiency and performance traits in beef cattle.

Discovery of genetic mutations that have a significant association with economically important traits would benefit beef cattle breeders. Objectives were to identify with an in silico approach new SNP in 8 genes involved in digestive function and metabolic processes and to examine the associations between the identified SNP and feed efficiency and performance traits. The association between SNP and daily DMI, ADG, midpoint metabolic weight (MMWT), residual feed intake (RFI), and feed conversion ratio (FCR; the ratio of average daily DMI to ADG) was tested in discovery and validation populations using a univariate mixed-inheritance animal model fitted in ASReml. Substitution effect of the T allele of SNP rs41256901 in protease, serine, 2 (trypsin 2; PRSS2) was associated with FCR (-0.293 ± 0.08 kg DMI kg(-1) BW gain; P < 0.001) and RFI (-0.199 ± 0.08 kg; P < 0.01) and although not significant in the validation population, the phase of association remained. In the cholecystokinin B receptor (CCKBR) gene, genotypes in rs42670351 were associated with RFI (P < 0.05) whereas genotypes in rs42670352 were associated with RFI (P = 0.002) and DMI (P < 0.05). Substitution of the G allele in rs42670352 was associated with DMI (-0.236 ± 0.12 kg; P = 0.055) and RFI (-0.175 ± 0.09 kg; P = 0.05). Substitution of the G allele of SNP rs42670353 was associated with ADG (0.043 ± 0.02 kg/d; P < 0.01) and FCR (0.114 ± 0.05 kg BW gain kg(-1) DMI; P < 0.05). In the validation dataset, SNP rs42670352 in gene CCKBR was significant for RFI and DMI and had the same phase of associations; SNP rs42670353 was significantly associated with FCR with same phase of association and the C allele in SNP rs42670351 was validated as decreasing DMI, RFI, and FCR. Substituting the G allele of SNP rs42670352 in CCKBR2 was associated with decreasing DMI and RFI in the validation study. New SNP were reported in genes PRSS2 and CCKBR, being associated with feed efficiency and performance traits in beef cattle. The association between these SNP with fertility, carcass, and meat quality traits must still be tested.

Abo-Ismail MK ，Kelly MJ ，Squires EJ ，Swanson KC ，Bauck S ，Miller SP ... -  《-》

Identification of polymorphisms influencing feed intake and efficiency in beef cattle.

Feed efficiency is an economically important trait in beef cattle. Net feed efficiency, measured as residual feed intake (RFI), is the difference between actual feed intake and the predicted feed intake required for maintenance and gain of the animal. SNPs that show associations with RFI may be useful quantitative trait nucleotides for marker-assisted selection. This study identified associations between SNPs underlying five RFI QTL on five bovine chromosomes (BTA2, 5, 10, 20 and 29) with measures of dry matter intake (DMI), RFI and feed conversion ratio (FCR) in beef cattle. Six SNPs were found to have effects on RFI (P < 0.05). The largest single SNP allele substitution effect for RFI was -0.25 kg/day located on BTA2. The combined effects of the SNPs found significant in this experiment explained 6.9% of the phenotypic variation of RFI. Not all the RFI SNPs showed associations with DMI and FCR even though these traits are highly correlated with RFI (r = 0.77 and r = 0.62 respectively). This shows that these SNPs may be affecting the underlying biological mechanisms of feed efficiency beyond feed intake control and weight gain efficiency. These SNPs can be used in marker-assisted selection but first it will be important to verify these effects in independent populations of cattle.

Sherman EL ，Nkrumah JD ，Murdoch BM ，Moore SS ... -  《-》

Whole genome single nucleotide polymorphism associations with feed intake and feed efficiency in beef cattle.

Feed intake and efficiency are economically important traits because feed is the greatest variable cost in beef production. Feed efficiency can be measured as residual feed intake (RFI), which is the difference between actual DMI of an animal and the expected DMI based on its BW and growth rate. Feed conversion ratio (FCR) is the inverse of gross feed efficiency and is the ratio of DMI to ADG. A total of 2,633 SNP across the 29 bovine autosomes were analyzed in 464 steers sired by Angus, Charolais, or Alberta Hybrid bulls for associations with RFI. A total of 150 SNP were associated with RFI at P < 0.05 of which 23 were significant at P < 0.01. Nine of the SNP pairs show high linkage disequilibrium (r(2) > 0.80), so only 1 of the SNP pairs was used in further multiple-marker analyses. Two methods were used to create a panel of SNP that were maximally informative for RFI based on the data. In the first method, 141 unique SNP were combined in a single multivariate model and a backward elimination model was used to drop SNP until all SNP left in the model were significant at P < 0.05. The SNP had greater effects when combined in the multivariate model than when tested individually. In the second method, the estimates from the 141 SNP were used to create a sequential molecular breeding value (MBV) according to the compound covariate prediction (CCP) procedure. The sequential MBV was built by adding the estimated effects one at a time, but only keeping SNP effects in the sequential MBV if the test statistic and the proportion of variance explained were improved. Predictabilities of the 2 methods were compared by regressing RFI on a final MBV created from SNP that remained in each analytical model. The MBV from the compound covariate prediction model produced an r(2) of 0.497, whereas the multivariate model MBV had a decreased r(2) of 0.416. The significant SNP were also tested for associations with DMI and FCR. The SNP showed different combinations of associations with the 4 traits, including some that were only associated with RFI. About 9.5% of the SNP from the 2 models were within 5 cM of previously identified RFI QTL and pinpoint areas to further explore for positional candidate genes. In conclusion, this study has identified a panel of SNP with significant effects on RFI that need to be validated in an independent population and provides continued progress toward selecting markers for use in marker-assisted selection for feed efficiency in beef cattle.

Sherman EL ，Nkrumah JD ，Moore SS 《-》

Development and validation of a small SNP panel for feed efficiency in beef cattle.

The objective of this study was to develop and validate a customized cost-effective single nucleotide polymorphism (SNP) panel for genetic improvement of feed efficiency in beef cattle. The SNPs identified in previous association studies and through extensive analysis of candidate genomic regions and genes, were screened for their functional impact and allele frequency in Angus and Hereford breeds used as validation candidates for the panel. Association analyses were performed on genotypes of 159 SNPs from new samples of Angus (n = 160), Hereford (n = 329), and Angus-Hereford crossbred (n = 382) cattle using allele substitution and genotypic models in ASReml. Genomic heritabilities were estimated for feed efficiency traits using the full set of SNPs, SNPs associated with at least one of the traits (at P ≤ 0.05 and P < 0.10), as well as the Illumina bovine 50K representing a widely used commercial genotyping panel. A total of 63 SNPs within 43 genes showed association (P ≤ 0.05) with at least one trait. The minor alleles of SNPs located in the GHR and CAST genes were associated with decreasing effects on residual feed intake (RFI) and/or RFI adjusted for backfat (RFIf), whereas minor alleles of SNPs within MKI67 gene were associated with increasing effects on RFI and RFIf. Additionally, the minor allele of rs137400016 SNP within CNTFR was associated with increasing average daily gain (ADG). The SNPs genotypes within UMPS, SMARCAL, CCSER1, and LMCD1 genes showed significant over-dominance effects whereas other SNPs located in SMARCAL1, ANXA2, CACNA1G, and PHYHIPL genes showed additive effects on RFI and RFIf. Gene enrichment analysis indicated that gland development, as well as ion and cation transport are important physiological mechanisms contributing to variation in feed efficiency traits. The study revealed the effect of the Jak-STAT signaling pathway on feed efficiency through the CNTFR, OSMR, and GHR genes. Genomic heritability using the 63 significant (P ≤ 0.05) SNPs was 0.09, 0.09, 0.13, 0.05, 0.05, and 0.07 for ADG, dry matter intake, midpoint metabolic weight, RFI, RFIf, and backfat, respectively. These SNPs contributed to genetic variation in the studied traits and thus can potentially be used or tested to generate cost-effective molecular breeding values for feed efficiency in beef cattle.

Abo-Ismail MK ，Lansink N ，Akanno E ，Karisa BK ，Crowley JJ ，Moore SS ，Bork E ，Stothard P ，Basarab JA ，Plastow GS ... -  《-》