Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria.

BACKGROUND: Bovine TB (bTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production. The key innate immune cell that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection. RESULTS: The host gene expression data consisted of RNA-seq data from bovine alveolar macrophages (bAM) infected with M. bovis at 24 and 48 h post-infection (hpi) compared to non-infected control bAM. These RNA-seq data were analysed using three distinct computational pipelines to produce six separate gene sets: 1) DE genes filtered using stringent fold-change and P-value thresholds (DEG-24: 378 genes, DEG-48: 390 genes); 2) genes obtained from expression correlation networks (CON-24: 460 genes, CON-48: 416 genes); and 3) genes obtained from differential expression networks (DEN-24: 339 genes, DEN-48: 495 genes). These six gene sets were integrated with three bTB breed GWAS data sets by employing a new genomics data integration tool-gwinteR. Using GWAS summary statistics, this methodology enabled detection of 36, 102 and 921 prioritised SNPs for Charolais, Limousin and Holstein-Friesian, respectively. CONCLUSIONS: The results from the three parallel analyses showed that the three computational approaches could identify genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets. These analyses also demonstrated significant differences among breeds, with the Holstein-Friesian breed GWAS proving most useful for prioritising SNPS through data integration. Because the functional genomics data were generated using bAM from this population, this suggests that the genomic architecture of bTB resilience traits may be more breed-specific than previously assumed.

Carcass and efficiency metrics of beef cattle differ by whether the calf was born in a dairy or a beef herd.

Beef originates from the progeny of either dairy or beef dams. The objective of the present study was to identify contributing factors to the differences in the carcass merit of progeny from both dam types. This goal was achieved using slaughter records from 16,414 bucket-reared dairy animals (DXD), 5,407 bucket-reared dairy-beef animals (BXD), 42,102 suckle-reared animals from a beef × dairy F1 cross dam (BXF1), and 93,737 suckle-reared animals from a beef × beef cow (BXB). Linear mixed models were used to quantify the least squares means for carcass characteristics in the various progeny genotypes. Nuisance fixed effects adjusted for in the models were: animal heterosis and recombination loss, dam parity, age at slaughter, and contemporary group; age at slaughter was replaced as an independent variable with both carcass weight and carcass fat score where the dependent variable was age at slaughter. In a follow-up analysis, models were re-analyzed where the genetic merit of the sire was adjusted for; a further analysis set the genetic merit of the dam for the dependent variable to be identical for both the dairy and beef dams. The final analysis adjusted to a common sire and dam genetic merit facilitating the estimation of just differences in early-life rearing strategies. Irrespective of the genetic merit of the sire and dam, animals originating from beef herds had heavier and more conformed carcasses. BXB animals had a 67 kg heavier carcass, with a conformation score (scale 1 [poor] to 15 [excellent]) of 5 units greater compared with DXD animals. When the genetic merit of all dams was set to be equal, BXB animals were heavier and better conformed than BXD animals. When the genetic merit for both the sire and dam were set to be equal, carcasses of the BXB animals were 15 kg heavier, with a 0.69 unit superior conformation score compared with the DXD animals; this difference is due to early life experiences. In conclusion, the majority of the inferiority in carcass metrics of calves from dairy herds compared with beef herds is due to differences in the genetic merit of the parents. Nevertheless, even after adjusting the parents to the same genetic merit, progeny from dairy herds were still inferior to their contemporaries born in beef herds, due most likely to the persistence of early life experiences.

Genetic parameters for variability in the birth of persistently infected cattle following likely in utero exposure to bovine viral diarrhea virus.

Genetic selection is an inexpensive and complementary strategy to traditional methods of improving animal health and welfare. Nonetheless, endeavors to incorporate animal health and welfare traits in international breeding programs have been hampered by the availability of informative phenotypes. The recent eradication program for bovine viral diarrhea (BVD) in the Republic of Ireland has provided an opportunity to quantify the potential benefits that genetic selection could offer BVD eradication programs elsewhere, as well as inform possible eradication programs for other diseases in the Republic of Ireland. Using a dataset of 188,085 Irish calves, the estimated direct and maternal heritability estimates for the birth of persistently infected calves following likely in utero exposure to BVD virus ranged from not different from zero (linear model) to 0.29 (SE = 0.075; threshold model) and from essentially zero (linear model) to 0.04 (SE = 0.033; threshold model), respectively. The corresponding genetic SD for the direct and maternal effect of the binary trait (0, 1) ranged from 0.005 (linear model) to 0.56 (threshold model) units and ranged from 0.00008 (linear model) to 0.20 (threshold model) units, respectively. The coefficient of direct genetic variation based on the linear model was 2.56% indicating considerable genetic variation could be exploited. Based on results from the linear model in the present study, there is the potential to reduce the incidence of persistent infection in cattle by on average 0.11 percentage units per year which is cumulative and permanent. Therefore, genetic selection can contribute to reducing the incidence of persistent infection in cattle. Moreover, where populations are free from persistent infection, inclusion of the estimated genetic merit for BVD in national breeding indexes could contribute to a preservation of a BVD-free status. Results from the present study can be used to inform breeding programs of the potential genetic gains achievable. Moreover, the approaches used in the present study can be applied to other diseases when data become available.