Dataset Information

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

ABSTRACT: BACKGROUND:Bovine 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. RESULTS:Genome 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. CONCLUSIONS:Although 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.

SUBMITTER: Kramer LM

PROVIDER: S-EPMC6325805 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Genome-wide association study for response to vaccination in Angus calves<sup>1</sup>.

Kramer L M LM Mayes M S MS Downey E D ED Tait R G RG Woolums A A Chase C C Reecy J M JM

BMC genetics 20190108 1

<h4>Background</h4>Bovine 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 t ...[more]

PMID: 30621575

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Project description:Beef cow stayability is a complex, economically important trait often used as an indicator of a cow's potential lifetime productivity. Stayability is defined as capability of a cow to maintain a perfect record up to 6 yr of age. This age is commonly cited as a financial break-even point, where initial costs of cow development and maintenance are recovered by her cumulative net income from yearly calf receipts. Later-maturing Bos indicus-Bos taurus crossbred cows may experience reproductive difficulty early in life but have a high potential for a long reproductive life span. It was the objective of this study to identify genetic variants associated with measures of beef cow stayability. A population of B. indicus-B. taurus crossbred cows (n = 305) from central Texas was used. Phenotypes for various measures of stayability to 6 yr of age were produced by artificially imposing five different culling criteria on data from the population. Cows were scored either as a 1 (indicating a perfect record through 6 yr) or a 0 (indicating failure at or before 6 yr), under each criterion. Genome-wide association studies (GWAS) were conducted for each criterion using univariate procedures and prefitting the fixed effect of cow contemporary group. SNP associations for two criteria surpassed the false discovery threshold of 0.15, when a cow was scored as 0 upon her first failure to wean a calf, regardless of reason, through 6 yr (criterion 2), and when a cow was scored as 0 upon her first failure to give birth to a calf, through 6 yr (criterion 3). Associated SNP were found on bovine chromosomes (BTA) 1, 2, 5, 9, 18, and 21 for criterion 2 and on BTA 1, 5, 11, 15, and 24 for criterion 3. A critical region on BTA 5: 43-50 Mb was identified for each criterion. Due to the similarities to prior work, the tendency for B. indicus cattle to experience reproductive difficulties early in life, and due to the large proportion of cows that left the herd at an early age under these criteria, these results suggest that the associations are likely driven by an early life trait such as age at puberty or rate of heifer development.

Project description:BACKGROUND: Breeding 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. RESULTS: A 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 ?-defensin. CONCLUSIONS: The 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.

Project description:We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n = 711) revealed GWAS significance (P = 1.60 × 10(-8)) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n = 870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P = 3.57 × 10(-8)). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20-0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.

Dataset Information

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

Publications

Genome-wide association study for response to vaccination in Angus calves<sup>1</sup>.

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