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

doi:10.1186/s12864-018-5062-6

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

BMC Genomics. 2018 Sep 21;19(1):694. doi: 10.1186/s12864-018-5062-6.

Authors

Britt de Klerk¹, Mehdi Emam^{2

3}, Kathleen A Thompson-Crispi⁴, Mehdi Sargolzaei^{2

5}, Johan J van der Poel¹, Bonnie A Mallard^{6

7}

Affiliations

¹ Animal Breeding and Genomics Centre, Wageningen University, P.O. Box 338, Wageningen, The Netherlands.
² Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, Canada.
³ Department of Pathobiology, Ontario Veterinary College, Genetic improvement of livestock, University of Guelph, Guelph, ON, N1G 2W1, Canada.
⁴ Trouw Nutrition Canada Inc., 150 Research Lane, Suite 200, Guelph, ON, N1G 4T2, Canada.
⁵ Semex Alliance, Guelph, ON, Canada.
⁶ Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, Canada. bmallard@ovc.uoguelph.ca.
⁷ Department of Pathobiology, Ontario Veterinary College, Genetic improvement of livestock, University of Guelph, Guelph, ON, N1G 2W1, Canada. bmallard@ovc.uoguelph.ca.

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.

Keywords: Dairy cattle; Genome-wide-association study; Immune system; Immunoglobulin class switching; Natural antibody; Vesicle trafficking.

MeSH terms

Animals
Antibodies / blood*
Antibodies / genetics
Antibodies / immunology
Canada
Cattle / blood
Cattle / genetics*
Female
Genome-Wide Association Study / methods*
Genotype
Immunoglobulin G / blood
Immunoglobulin G / genetics*
Immunoglobulin G / immunology
Immunoglobulin M / blood
Immunoglobulin M / genetics*
Immunoglobulin M / immunology
Male
Polymorphism, Single Nucleotide*

Substances

Antibodies
Immunoglobulin G
Immunoglobulin M