An across-breed genome wide association analysis of susceptibility to paratuberculosis in dairy cattle

Sallam, Ahmed M.; Zare, Yalda; Alpay, Fazli; Shook, G.E.; Collins, Michael T.; Alsheikh, S. M.; Sharaby, Mahmoud A.; Kirkpatrick, Brian

doi:10.1017/s0022029916000807

Cited by 20 publications

(20 citation statements)

References 22 publications

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“…Color version available online. Candidate genes BTA1 Settles et al, 2009;Pant et al, 2010;Zanella et al, 2011;Minozzi et al, 2012;Alpay et al, 2014;Zare et al, 2014aSOD1, SSRG, SCL33A1, LDLRAD3, KCNAB1, GMPS, TUBA3D BTA2 Kirkpatrick et al, 2011Alpay et al, 2014;Sallam et al, 2017CREB1 BTA3 Settles et al, 2009Kirkpatrick et al, 2011;Zare et al, 2014b;Kiser et al, 2017FOXJ3, EDN2, CTPS, CITED4, NFYC, BCAR3 BTA4 Kirkpatrick et al, 2011van Hulzen et al, 2012DLD, Q28899, LAMB4, Q6Q146, PNPLA8, LOC784535, Q2YDK7, Q17QP5, EPDR1 BTA5 Settles et al, 2009Pant et al, 2010;Kirkpatrick et al, 2011;...…”

Section: Gwas and Functional Analysesmentioning

confidence: 99%

The genetic architecture of milk ELISA scores as an indicator of Johne's disease (paratuberculosis) in dairy cattle

Brito

Mallikarjunappa

Sargolzaei

et al. 2018

Journal of Dairy Science

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Johne's disease (or paratuberculosis), caused by Mycobacterium avium ssp. paratuberculosis (MAP) infection, is a globally prevalent disease with severe economic and welfare implications. With no effective treatment available, understanding the role of genetics influencing host infection status is essential to develop selection strategies to breed for increased resistance to MAP infection. The main objectives of this study were to estimate genetic parameters for the MAP-specific antibody response using milk ELISA scores in Canadian Holstein cattle as an indicator of resistance to Johne's disease, and to unravel genomic regions and candidate genes significantly associated with MAP infection. After data editing, 168,987 milk ELISA records from 2,306 herds, obtained from CanWest Dairy Herd Improvement, were used for further analyses. Variance and heritability estimates for MAP infection status were determined using univariate linear animal models under 3 scenarios: (a) SCEN1: the complete data set (all herds); (b) SCEN2: herds with at least one suspect or test-positive animal (ELISA optical density ≥0.07); and (c) SCEN3: herds with at least one test-positive animal (ELISA optical density ≥0.11). Heritability estimates were calculated as 0.066, 0.064, and 0.063 for SCEN1, SCEN2, and SCEN3, respectively. The correlations between estimated breeding values for resistance to MAP infection and other economically important traits, when significant, were favorable and of low magnitude. Genome-wide association analyses identified important genomic regions on Bos taurus autosome (BTA)1, BTA7, BTA9, BTA14, BTA15, BTA17, BTA19, and BTA25 showing significant association with MAP infection status. These regions included 2 single nucleotide polymorphisms located 2 kb upstream of positional candidate genes CD86 and WNT9B, which play key roles in host immune response and tissue homeostasis. This study revealed the genetic architecture of MAP infection in Canadian Holstein cattle as measured by milk ELISA scores by estimating genetic parameters along with the identification of genomic regions potentially influencing MAP infection status. These findings will be of significant value toward implementing genetic and genomic evaluations for resistance to MAP infection in Holstein cattle.

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Section: Gwas and Functional Analysesmentioning

confidence: 99%

The genetic architecture of milk ELISA scores as an indicator of Johne's disease (paratuberculosis) in dairy cattle

Brito

Mallikarjunappa

Sargolzaei

et al. 2018

Journal of Dairy Science

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“…Other studies have also investigated the genetic architecture of MAP infection status in cattle. Significant genomic regions have been reported on various chromosomes such as BTA1 (Alpay et al, 2014), BTA2 (Alpay et al, 2014;Sallam et al, 2017), BTA3 (Settles et al, 2009;Zare et al, 2014;Sallam et al, 2017), BTA4 and BTA5 (van Hulzen et al, 2012), BTA6 (Alpay et al, 2014;Sallam et al, 2017), BTA7 (Alpay et al, 2014), BTA8 (Kiser et al, 2017;Sallam et al, 2017), BTA9 (Settles et al, 2009), BTA10, BTA12, and BTA14 (Kiser et al, 2017), BTA16 (Zare et al, 2014;Kiser et al, 2017), BTA17 (Alpay et al, 2014;Zare et al, 2014), BTA18 (van Hulzen et al, 2012), BTA20 (Gonda et al, 2007), BTA22 (Kiser et al, 2017), BTA23 (Zare et al, 2014), BTA25 and BTA27 (Sallam et al, 2017), BTA28 (van Hulzen et al, 2012), and BTA29 (Alpay et al, 2014;Sallam et al, 2017).…”

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confidence: 99%

“…In comparison with this study, 2 recently published GWAS identified different positional candidate genes and QTL associated with JD. By conducting a combined across-breed GWAS, Sallam et al (2017) identified QTL on BTA2, BTA3, BTA6, BTA8, BTA25, BTA27, and BTA29 and also reported 2 positional candidate genes, BTN1A1 and TDP2, associated with JD (cases were defined as cows that were positive by either fecal culture or serum ELISA tests). In an another GWAS using BovineSNP50 data, where JD cases were defined as MAP tissue quantitative PCR and culture positive, Kiser et al (2017) identified 7 QTL located on BTA22 in Jerseys and 6 QTL located on BTA8, BTA10, BTA12, BTA14, and BTA16 in the combined Pacific Northwest and Northeast Holstein population by meta-analysis.…”

mentioning

confidence: 99%

Short communication: Uncovering quantitative trait loci associated with resistance to Mycobacterium avium ssp. paratuberculosis infection in Holstein cattle using a high-density single nucleotide polymorphism panel

Mallikarjunappa

Sargolzaei

Brito

et al. 2018

Journal of Dairy Science

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Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of Johne's disease in cattle. Johne's disease is a disease of significant economic, animal welfare, and public health concern around the globe. Therefore, understanding the genetic architecture of resistance to MAP infection has great relevance to advance genetic selection methods to breed more resistant animals. The objectives of this study were to perform a genome-wide association study of previously analyzed 50K genotypes now imputed to a high-density single nucleotide polymorphism panel (777K), aiming to validate previously reported associations and potentially identify additional single nucleotide polymorphisms associated with antibody response to MAP infection. A principal component regression-based genome-wide association study revealed 15 putative quantitative trait loci (QTL) associated with the MAP infection phenotype (serum or milk ELISA tests) on 9 different chromosomes (Bos taurus autosomes 5, 6, 7, 10, 14, 15, 16, 20, and 21). These results validated previous findings and identified new QTL on Bos taurus autosomes 15, 16, 20, and 21. The positional candidate genes NLRP3, IFi47, TRIM41, TNFRSF18, and TNFRSF4 lying within these QTL were identified. Further functional validation of these genes is now warranted to investigate their roles in regulating the immune response and, consequently, cattle resistance to MAP infection.

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“…2, 3, 4, 5). The polygenic nature of viral neutralization antibody level, response to vaccination, and immune related traits is something that has been previously reported in numerous studies such as those focused on porcine [17, 25], chicken [26, 27], cattle [28–31], and mice [32]. In the six windows that accounted for more than 1% of the genetic variance in this study, no candidate genes were identified as none of the genes in those regions were annotated with Gene Ontology terms associated with immune response functions.…”

Section: Discussionmentioning

confidence: 93%

Genome-wide association study for response to vaccination in Angus calves1

et al. 2019

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BackgroundBovine respiratory disease complex (BRDC) is one of the most important sources of loss within the beef cattle industry in the USA. Steps have been taken to reduce the incidence of BRDC through vaccination. Despite the effectiveness of vaccines, large proportions of cattle still experience morbidity and mortality. Identification of genomic regions that are associated with variation in response to vaccination would allow for the selection of individuals genetically predisposed to respond to vaccination based on specific markers, while heritability and accuracy estimates would help facilitate genomic selection. This in turn may lead to selection for beef cattle herds that may have lower incidence rate of BRDC after vaccination. This study utilizes an Angus herd of more than 2000 head of cattle to identify these regions of association.ResultsGenome wide association studies were performed for viral neutralization antibody level and response to vaccination traits against four different viruses associated with BRDC: bovine viral diarrhea virus 1 and 2 (BVDV1 and BVDV2), bovine respiratory syncytial virus (BRSV), and bovine herpesvirus (BHV1). A total of six 1-Mb windows were associated with greater than 1% of the genetic variance for the analyzed vaccination response traits. Heritabilities ranged from 0.08 to 0.21 and prediction accuracy ranged from 0.01 to 0.33 across 7 different vaccination traits.ConclusionsAlthough six 1-Mb windows were identified as associated with 1% or greater genetic variance for viral neutralization antibody level and response to vaccination traits, few genes around these windows could readily be considered candidates. This indicates the need for further functional genomic annotation, as these regions appear to be gene deserts. Traits ranged from lowly to moderately heritable, which indicated the potential for selection of individuals that are genetically pre-disposed to respond to vaccination. The relatively low amount of genetic variance accounted for by any 1-Mb window indicated that viral neutralization antibody level and response to vaccination traits are polygenic in nature. Selection for these traits is possible, but likely to be slow due to the low heritabilities and absence of markers with high genetic variation associated with them.

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An across-breed genome wide association analysis of susceptibility to paratuberculosis in dairy cattle

Cited by 20 publications

References 22 publications

The genetic architecture of milk ELISA scores as an indicator of Johne's disease (paratuberculosis) in dairy cattle

The genetic architecture of milk ELISA scores as an indicator of Johne's disease (paratuberculosis) in dairy cattle

Short communication: Uncovering quantitative trait loci associated with resistance to Mycobacterium avium ssp. paratuberculosis infection in Holstein cattle using a high-density single nucleotide polymorphism panel

Genome-wide association study for response to vaccination in Angus calves1

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