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

Abstract

BackgroundNatural 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.ResultsIn 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5062-6) contains supplementary material, which is available to authorized users.

Genome-Wide Association Studies for Immunoglobulins in Colostrum and Serum in Chinese Holstein

“…Also, the identi ed signi cant SNPs for IgM in colostrum and serum were totally different. Similar results were reported in a previous GWAS by de Klerk et al [12]. As for the other genomic regions we identi ed for immunoglobulins have not been reported in previous studies in bovine.…”

“…This setting of thresholds may lead slight false positive but numerous useful information.In this GWAS, we found a region on BTA-21 from 63.9 to 71.5Mb that was signi cantly associated with for IgG2. Previous GWASs on bovine nature antibodies in Canadian and Dutch Holstein populations identi ed genomic regions on BTA-21 from 55.5 to 70.6 Mb and 66.0 to 71.6 Mb that were signi cantly associated with KLH-IgG and PGN-IgG1[12,20], which overlapped with region in this study. Although our samples were taken from colostrum and serum, whereas theirs were from serum and mature milk, and we analyzed IgG, IgG1 and IgG2 while they analyzed IgG and IgG1, it is likely due to the high genetic correlation between the same IgG…”

“…Heritability estimates for IgG concentrations in blood ranged from 0.27 to 0.64 in human [8][9][10][11][12]. In dairy cows, heritability estimates of immunoglobulins measured in blood or milk ranges from 0.08-0.45 [13][14][15][16], where IgM generally has the highest heritability estimates (0.18-0.45) and IgG has lower heritability estimates (0.08-0.31).…”

“…In pig, 4 signi cant SNPs were identi ed by GWAS performed for four traits, including interferon-gamma (IFN-c) and interleukin 10 (IL-10) levels, the ratio of IFN-c to IL-10 and IgG blocking percentage to CSFV in serum [19]. Especially, a previous GWAS for blood natural antibodies in Canadian Holstein cows found the 23 SNPs were signi cantly associated with IgG [12]. Another GWAS for milk natural antibodies in Dutch Holstein-Friesian cattle identi ed candidate genes on chromosome 17, 18, and 21 that related to immunoglobulin structure and early B cell development [20].…”

Genome-Wide Association Studies for Immunoglobulin Concentrations in Colostrum and Serum in Chinese Holstein

“…In pigs, 2 genome-wide and 4 chromosome-wide signi cant SNPs were detected for IgG blocking percentage to CSF virus in serum by performing GWAS [16]. Especially, a GWAS for blood natural antibodies in Canadian Holstein cows identi ed 23 SNPs that were signi cantly associated with IgG concentration at genome-wide level [17]. Another GWAS for milk natural antibodies in Dutch Holstein-Friesian cattle identi ed some signi cant SNPs for IgG1 and IgM with candidate genes on Bos taurus autosome (BTA) 3, 17, 18, and 21 that related to immunoglobulin structure and early B cell development [18].…”