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

Britt de Klerk, Mehdi Emam, Kathleen A. Thompson-Crispi, Mehdi Sargolzaei, Johan J. van der Poel, Bonnie A. Mallard*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

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 < 0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of the cow genome. Functional annotation analysis of the positional candidate genes revealed two sets of genes with biologically relevant functions related to NAb. In one set, seven genes with crucial roles in the production of antibody in B cells were associated with the trafficking of vesicles inside the cells between organelles. In the second set, two genes among positional candidate genes were associated with isotype class-switching and somatic hypermutation of B cells. Conclusions: This study demonstrated the possibility of increasing NAb through selective breeding. In addition, the effects of two candidate pathways are proposed for further investigation of NAb production in Holsteins.

Original languageEnglish
Article number624
JournalBMC Genomics
Volume19
Issue number1
DOIs
Publication statusPublished - 21 Sep 2018

Fingerprint

Genome-Wide Association Study
Antibodies
Immunoglobulin Class Switching
Single Nucleotide Polymorphism
Immunoglobulin M
Immunoglobulin G
Genes
Antibody Formation
B-Lymphocytes
Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 21
Disease Resistance
Immunoglobulin Isotypes
Chromosomes, Human, Pair 1
Genetic Association Studies
Innate Immunity
Organelles
Immune System
Enzyme-Linked Immunosorbent Assay
Genome

Keywords

  • Dairy cattle
  • Genome-wide-association study
  • Immune system
  • Immunoglobulin class switching
  • Natural antibody
  • Vesicle trafficking

Cite this

de Klerk, B., Emam, M., Thompson-Crispi, K. A., Sargolzaei, M., van der Poel, J. J., & Mallard, B. A. (2018). A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows. BMC Genomics, 19(1), [624]. https://doi.org/10.1186/s12864-018-5062-6
de Klerk, Britt ; Emam, Mehdi ; Thompson-Crispi, Kathleen A. ; Sargolzaei, Mehdi ; van der Poel, Johan J. ; Mallard, Bonnie A. / A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows. In: BMC Genomics. 2018 ; Vol. 19, No. 1.
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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 < 0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of the cow genome. Functional annotation analysis of the positional candidate genes revealed two sets of genes with biologically relevant functions related to NAb. In one set, seven genes with crucial roles in the production of antibody in B cells were associated with the trafficking of vesicles inside the cells between organelles. In the second set, two genes among positional candidate genes were associated with isotype class-switching and somatic hypermutation of B cells. Conclusions: This study demonstrated the possibility of increasing NAb through selective breeding. In addition, the effects of two candidate pathways are proposed for further investigation of NAb production in Holsteins.",
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de Klerk, B, Emam, M, Thompson-Crispi, KA, Sargolzaei, M, van der Poel, JJ & Mallard, BA 2018, 'A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows', BMC Genomics, vol. 19, no. 1, 624. https://doi.org/10.1186/s12864-018-5062-6

A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows. / de Klerk, Britt; Emam, Mehdi; Thompson-Crispi, Kathleen A.; Sargolzaei, Mehdi; van der Poel, Johan J.; Mallard, Bonnie A.

In: BMC Genomics, Vol. 19, No. 1, 624, 21.09.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows

AU - de Klerk, Britt

AU - Emam, Mehdi

AU - Thompson-Crispi, Kathleen A.

AU - Sargolzaei, Mehdi

AU - van der Poel, Johan J.

AU - Mallard, Bonnie A.

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N2 - 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 < 0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of the cow genome. Functional annotation analysis of the positional candidate genes revealed two sets of genes with biologically relevant functions related to NAb. In one set, seven genes with crucial roles in the production of antibody in B cells were associated with the trafficking of vesicles inside the cells between organelles. In the second set, two genes among positional candidate genes were associated with isotype class-switching and somatic hypermutation of B cells. Conclusions: This study demonstrated the possibility of increasing NAb through selective breeding. In addition, the effects of two candidate pathways are proposed for further investigation of NAb production in Holsteins.

AB - 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 < 0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of the cow genome. Functional annotation analysis of the positional candidate genes revealed two sets of genes with biologically relevant functions related to NAb. In one set, seven genes with crucial roles in the production of antibody in B cells were associated with the trafficking of vesicles inside the cells between organelles. In the second set, two genes among positional candidate genes were associated with isotype class-switching and somatic hypermutation of B cells. Conclusions: This study demonstrated the possibility of increasing NAb through selective breeding. In addition, the effects of two candidate pathways are proposed for further investigation of NAb production in Holsteins.

KW - Dairy cattle

KW - Genome-wide-association study

KW - Immune system

KW - Immunoglobulin class switching

KW - Natural antibody

KW - Vesicle trafficking

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de Klerk B, Emam M, Thompson-Crispi KA, Sargolzaei M, van der Poel JJ, Mallard BA. A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows. BMC Genomics. 2018 Sep 21;19(1). 624. https://doi.org/10.1186/s12864-018-5062-6