Mohammed Abo-Ismail

A genome-wide association study of immune response traits in Canadian Holstein cattle

BackgroundBreeding 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.ResultsA 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 β-defensin.ConclusionsThe 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.

Single nucleotide polymorphisms for feed efficiency and performance in crossbred beef cattle.

BackgroundThis study was conducted to: (1) identify new SNPs for residual feed intake (RFI) and performance traits within candidate genes identified in a genome wide association study (GWAS); (2) estimate the proportion of variation in RFI explained by the detected SNPs; (3) estimate the effects of detected SNPs on carcass traits to avoid undesirable correlated effects on these economically important traits when selecting for feed efficiency; and (4) map the genes to biological mechanisms and pathways. A total number of 339 SNPs corresponding to 180 genes were tested for association with phenotypes using a single locus regression (SLRM) and genotypic model on 726 and 990 crossbred animals for feed efficiency and carcass traits, respectively.ResultsStrong evidence of associations for RFI were located on chromosomes 8, 15, 16, 18, 19, 21, and 28. The strongest association with RFI (P = 0.0017) was found with a newly discovered SNP located on BTA 8 within the ELP3 gene. SNPs rs41820824 and rs41821600 on BTA 16 within the gene HMCN1 were strongly associated with RFI (P = 0.0064 and P = 0.0033, respectively). A SNP located on BTA 18 within the ZNF423 gene provided strong evidence for association with RFI (P = 0.0028). Genomic estimated breeding values (GEBV) from 98 significant SNPs were moderately correlated (0.47) to the estimated breeding values (EBVs) from a mixed animal model. The significant (P < 0.05) SNPs (98) explained 26% of the genetic variance for RFI. In silico functional analysis for the genes suggested 35 and 39 biological processes and pathways, respectively for feed efficiency traits.ConclusionsThis study identified several positional and functional candidate genes involved in important biological mechanisms associated with feed efficiency and performance. Significant SNPs should be validated in other populations to establish their potential utilization in genetic improvement programs.

Genome-wide association for milk production and female fertility traits in Canadian dairy Holstein cattle

BackgroundGenome-wide association studies (GWAS) are a powerful tool for detecting genomic regions explaining variation in phenotype. The objectives of the present study were to identify or refine the positions of genomic regions affecting milk production, milk components and fertility traits in Canadian Holstein cattle, and to use these positions to identify genes and pathways that may influence these traits.ResultSeveral QTL regions were detected for milk production (MILK), fat production (FAT), protein production (PROT) and fat and protein deviation (FATD, PROTD respectively). The identified QTL regions for production traits (including milk production) support previous findings and some overlap with genes with known relevant biological functions identified in earlier studies such as DGAT1 and CPSF1. A significant region on chromosome 21 overlapping with the gene FAM181A and not previous linked to fertility in dairy cattle was identified for the calving to first service interval and days open. A functional enrichment analysis of the GWAS results yielded GO terms consistent with the specific phenotypes tested, for example GO terms GO:0007595 (lactation) and GO:0043627 (response to estrogen) for milk production (MILK), GO:0051057 (positive regulation of small GTPase mediated signal transduction) for fat production (FAT), GO:0040019 (positive regulation of embryonic development) for first service to calving interval (CTFS) and GO:0043268 (positive regulation of potassium ion transport) for days open (DO). In other cases the connection between the enriched GO terms and the traits were less clear, for example GO:0003279 (cardiac septum development) for FAT and GO:0030903 (notochord development) for DO trait.ConclusionThe chromosomal regions and enriched pathways identified in this study confirm several previous findings and highlight new regions and pathways that may contribute to variation in production or fertility traits in dairy cattle.

Influence of feeding increasing levels of dry corn distillers grains plus solubles in whole corn grain-based finishing diets on total tract digestion, nutrient balance, and excretion in beef steers.

Four crossbred steers (average BW = 478 ± 33 kg) were used in a 4 × 4 Latin square design to determine the effects of dietary concentration of dry corn distillers grains plus solubles (DDGS) in whole corn-based finishing diets on total tract digestion and nutrient balance and excretion. The DDGS were fed at 0% (control), 16.7%, 33.3%, and 50% of dietary DM. All diets contained 10% (DM basis) alfalfa/grass haylage and were formulated to meet or exceed the estimated requirements for CP. Steers were fed the experimental diets ad libitum for a 14-d adaptation period followed by a 5-d period for fecal and urine collection. Increasing concentration of DDGS in diets from 0 to 50% of DM linearly decreased (P < 0.05) total tract DM and starch digestibility (from 77.8 to 72.9%, and 89.2 to 81.5%, respectively). Daily N and P intakes linearly increased (P = 0.06 and P = 0.01, respectively) with increasing DDGS concentration. Fecal and urinary N, P, S, Mg, and K excretion linearly increased (P < 0.05) with increasing DDGS concentration; however, Se and Na excretion did not differ (P > 0.38) among treatments. Retention (g/d; intake minus urinary and fecal excretion) of N did not differ (P > 0.16) among treatments. Retention of P tended (P = 0.07) to linearly increase and retention of S (g/d) linearly increased (P = 0.004), with increasing DDGS concentration. There were no effects (P > 0.16) of dietary treatment on digestion and retention of Se, Mg, K, and Na. Plasma P and S concentrations increased (P = 0.03 and 0.01, respectively) with increasing DDGS concentration. These data indicate that feeding DDGS up to 50% of dietary DM in whole corn grain-based finishing diets does not have a negative effect on nutrient retention but decreases digestibility. Total excretion of N, P, Ca, Mg, S, and K increased as DDGS concentration increased.

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.

Genomic prediction of breed composition and heterosis effects in Angus, Charolais and Hereford crosses using 50K genotypes

Abstract This study examined the feasibility and accuracy of using Illumina BovineSNP50 genotypes to estimate individual cattle breed composition and heterosis relative to estimate from pedigree. First, pedigree was used to compute breed fractions for 1124 crossbred cattle. Given the breed composition of sires and dams, retained heterosis and retained heterozygosity were computed for all individuals. Second, all animals’ genotypes were used to compute individual’s genomic breed fractions by applying a cross-validation method. Average genome-wide heterozygosity and retained heterozygosity based on genomic breed fraction were computed. Lastly, accuracies of breed composition, retained heterozygosity and retained heterosis were assessed as Pearson’s correlation between pedigree- and genome-based predictions. The average breed compositions observed were 0.52 Angus, 0.23 Charolais, and 0.25 Hereford for pedigree-based prediction and 0.46, 0.26, and 0.28 for genome-based prediction, respectively. Correlations of predicted breed composition ranged from 0.94 to 0.96. Genome-based retained heterozygosity and retained heterosis from pedigree were also highly correlated (0.96). A positive association of nonadditive genetic effects was observed for growth traits reflecting the importance of heterosis for these traits. Genomic prediction can aid analyses that depend on knowledge of breed composition and serve as a reliable method to predict heterosis to improve the efficiency of commercial crossbreeding schemes.