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A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows.

ABSTRACT: BACKGROUND:Natural antibodies (NAb) are an important component of the innate immune system, and fight infections as a part of the first line defence. NAb are poly-reactive and can respond non-specifically to antigens. Therefore, NAb may be a key trait when evaluating an animal's potential natural disease resistance. Variation in NAb is caused by both genetic and environmental factors. In this study genetic parameters of NAb were estimated and a genome-wide association study (GWAS) was performed to gain further understanding on the genes that are responsible for the observed genetic variation of NAb in Canadian Holsteins. RESULTS:In total, blood samples of 1327 cows from 64 farms were studied. NAb binding to keyhole limpet hemocyanin (KLH) were determined via indirect ELISA. Immunoglobulin (Ig) isotypes, IgG and IgM, were evaluated. From the sample population, 925 cows were genotyped for 45,187 markers and each individual marker was tested to detect genetic variation in NAb levels. The relationships among animals was accounted for with genomic relationship. Results show heritabilities of 0.27?±?0.064 (IgG) and 0.31?±?0.065 (IgM). In total, 23 SNPs were found to be associated with IgG, but no SNPs were associated with IgM (FDR p-value

SUBMITTER: de Klerk B

PROVIDER: S-EPMC6150957 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows.

de Klerk Britt B Emam Mehdi M Thompson-Crispi Kathleen A KA Sargolzaei Mehdi M van der Poel Johan J JJ Mallard Bonnie A BA

BMC genomics 20180921 1

<h4>Background</h4>Natural antibodies (NAb) are an important component of the innate immune system, and fight infections as a part of the first line defence. NAb are poly-reactive and can respond non-specifically to antigens. Therefore, NAb may be a key trait when evaluating an animal's potential natural disease resistance. Variation in NAb is caused by both genetic and environmental factors. In this study genetic parameters of NAb were estimated and a genome-wide association study (GWAS) was pe ...[more]

PMID: 30241501

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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:BACKGROUND: Genome-wide association analysis is a powerful tool for annotating phenotypic effects on the genome and knowledge of genes and chromosomal regions associated with dairy phenotypes is useful for genome and gene-based selection. Here, we report results of a genome-wide analysis of predicted transmitting ability (PTA) of 31 production, health, reproduction and body conformation traits in contemporary Holstein cows. RESULTS: Genome-wide association analysis identified a number of candidate genes and chromosome regions associated with 31 dairy traits in contemporary U.S. Holstein cows. Highly significant genes and chromosome regions include: BTA13's GNAS region for milk, fat and protein yields; BTA7's INSR region and BTAX's LOC520057 and GRIA3 for daughter pregnancy rate, somatic cell score and productive life; BTA2's LRP1B for somatic cell score; BTA14's DGAT1-NIBP region for fat percentage; BTA1's FKBP2 for protein yields and percentage, BTA26's MGMT and BTA6's PDGFRA for protein percentage; BTA18's 53.9-58.7 Mb region for service-sire and daughter calving ease and service-sire stillbirth; BTA18's PGLYRP1-IGFL1 region for a large number of traits; BTA18's LOC787057 for service-sire stillbirth and daughter calving ease; BTA15's CD82, BTA23's DST and the MOCS1-LRFN2 region for daughter stillbirth; and BTAX's LOC520057 and GRIA3 for daughter pregnancy rate. For body conformation traits, BTA11, BTAX, BTA10, BTA5, and BTA26 had the largest concentrations of SNP effects, and PHKA2 of BTAX and REN of BTA16 had the most significant effects for body size traits. For body shape traits, BTAX, BTA19 and BTA3 were most significant. Udder traits were affected by BTA16, BTA22, BTAX, BTA2, BTA10, BTA11, BTA20, BTA22 and BTA25, teat traits were affected by BTA6, BTA7, BTA9, BTA16, BTA11, BTA26 and BTA17, and feet/legs traits were affected by BTA11, BTA13, BTA18, BTA20, and BTA26. CONCLUSIONS: Genome-wide association analysis identified a number of genes and chromosome regions associated with 31 production, health, reproduction and body conformation traits in contemporary Holstein cows. The results provide useful information for annotating phenotypic effects on the dairy genome and for building consensus of dairy QTL effects.

Dataset Information

A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows.

Publications

A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows.

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