Genome-Wide Association Analysis and Genomic Prediction of Mycobacterium avium Subspecies paratuberculosis Infection in US Jersey Cattle

Zare, Yalda; Shook, G.E.; Collins, Michael T.; Kirkpatrick, Brian

doi:10.1371/journal.pone.0088380

Cited by 46 publications

(40 citation statements)

References 68 publications

(85 reference statements)

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“…Our region was located about 10 Mb upstream of the MHC region based on GWA and 2 Mb based on RHM results. In addition, Zare et al [46] found genomic regions on BTA 23 (at 35.3 and 44.4 Mb) associated with paratuberculosis in Jersey cattle, a disease with certain similarities to bTB. These regions corresponded to our RHM identified regions on BTA 23.…”

Section: Discussionmentioning

confidence: 99%

Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle

et al. 2017

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BackgroundThe significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics.MethodsThe present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control.ResultsThe estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB.ConclusionGenomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-017-0493-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle

et al. 2017

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“…One of the most investigated traits was Johne's disease, a chronic gastrointestinal tract disease caused by Mycobacterium avium subspecies paratuberculosis. Several GWASs have been performed, mostly on naturally infected Holsteins and Jerseys (common breeds of dairy cattle): associated variants with small effect were identified in several analyses, but reproducibility among studies was extremely low, resulting in no confidently associated marker (Alpay et al, 2014;Kirkpatrick et al, 2011;Minozzi et al, 2010;Neibergs et al, 2010;Pant et al, 2010;Settles et al, 2009;van Hulzen et al, 2012;Zare et al, 2014). Although the reasons for low across-study consistency are likely manifold and include different criteria to classify phenotypes and different statistical procedures, these results suggest that loci with a major effect on Johne's disease do not exist, at least in these breeds.…”

Section: Gwass In Cattle and Swinementioning

confidence: 99%

Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches

Mozzi

Pontremoli

Sironi

2018

Infection, Genetics and Evolution

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Genome-wide association studies (GWASs) have been widely applied to identify genetic factors that affect complex diseases or traits. Presently, the GWAS Catalog includes >2800 human studies. Of these, only a minority have investigated the susceptibility to infectious diseases or the response to therapies for the treatment or prevention of infections. Despite their limited application in the field, GWASs have provided valuable insights by pinpointing associations to both innate and adaptive immune response loci, as well as novel unexpected risk factors for infection susceptibility. Herein, we discuss some issues and caveats of GWASs for infectious diseases, we review the most recent findings ensuing from these studies, and we provide a brief summary of selected GWASs for infections in non-human mammals. We conclude that, although the general trend in the field of complex traits is to shift from GWAS to next-generation sequencing, important knowledge on infectious disease-related traits can be still gained by GWASs, especially for those conditions that have never been investigated using this approach. We suggest that future studies will benefit from the leveraging of information from the host's and pathogen's genomes, as well as from the exploration of models that incorporate heterogeneity across populations and phenotypes. Interactions within HLA genes or among HLA variants and polymorphisms located outside the major histocompatibility complex may also play an important role in shaping the susceptibility and response to invading pathogens.

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“…The existing studies on immune response to infections, both in humans and in livestock, have compared the positive and the control groups using either the candidate gene approach, which is based on the analysis of pre-selected genes, or the GWAS, by exploiting anonymous marker panels of various density (Minozzi et al 2010;Nalpas et al 2013;Zare et al 2014). However, so far, little doi: 10.17221/30/2015-CJAS overall consensus has emerged from these studies in terms of resistance loci, this being likely due, according to Riggio et al (2014), to the apparent genetic complexity of the trait and the diversity of the studies, both for the considered breeds and the experimental approaches.…”

Section: Discussionmentioning

confidence: 99%

Identification of missense mutations in the PCP4 and CD109 genes to validate the effect of neutral genetic markers

Moioli¹,

Grossi²,

Steri³

et al. 2016

CZECH J ANIM SCI

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ABSTRACT:The marker-assisted selection exploits anonymous genetic markers that have been associated with measurable differences on complex traits. Because it is based on the linkage disequilibrium (LD) between the polymorphic markers and the polymorphisms which code for the trait, its success is limited to the population in which the association has been assessed. The identification of the gene with effect on the target trait and the detection of the functional mutations will allow selection in independent populations, while encouraging studies on gene expression. In a flock of sheep infected with M. paratuberculosis, a genome-wide scan, performed with the Illumina OvineSNP50 BeadChip, had identified two candidate genes, the PCP4 and the CD109, located in proximity of the markers with significant allele substitution effect on the positivity level at paratuberculosis serological assessment. The coding region of the two genes was directly sequenced. Three missense mutations were detected: two in the PCP4 gene and one in the second exon of the CD109 gene, the latter showing a strong LD with the anonymous marker. Direct sequencing of the DNA of sheep of different populations showed that disequilibrium was maintained. Allele frequency at the hypothesized marker associated to immune response, calculated for other breeds of sheep, showed that the marker allele potentially associated to disease resistance is more frequent in the local breeds and in breeds that have not been submitted to selection programs.

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Genome-Wide Association Analysis and Genomic Prediction of Mycobacterium avium Subspecies paratuberculosis Infection in US Jersey Cattle

Cited by 46 publications

References 68 publications

Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle

Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle

Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches

Identification of missense mutations in the PCP4 and CD109 genes to validate the effect of neutral genetic markers

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