- A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows. - Background: Natural antibodies (NAb) are an important component of the innate immune system, and fight infections as a part of the first line defence. - 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.. - Full list of author information is available at the end of the article. - 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0. - The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.. - In these studies, the relationships between economically important diseases, including mastitis, me- tritis, pneumonia, displaced abomasum and retained pla- centa of dairy cows and their immune responses were examined and it was demonstrated that specific anti- bodies (SpAb), which are part of the adaptive immune system, are useful biomarkers for disease resistance.. - However, SpAb are only measured after immunization of the cows, whereas NAb can be measured prior to immunization, and therefore may have practical advantages in a breeding program.. - Van Knegsel et al. - Banos et al. - hypothesized that higher NAb levels (binding to KLH) can be associated with improved capacity of the innate immune system to respond to pathogen challenges. - The objective of this study was to identify regions of the bovine genome that are associated with the level of NAb of the IgM and IgG isotypes. - average of 53,583 bp on each side of the significant SNPs. - Natural antibodies are considered as. - the humoral part of the innate immune system [6]. - In this study to identify candidate regions, the immediate adjacent SNPs on each side of the significant SNPs were selected, in- stead of selecting a fixed size. - 2 ARS-BFGL-NGS E-02. - 3 ARS-BFGL-NGS E-02. - 5 ARS-BFGL-NGS E-03. - 6 ARS-BFGL-NGS E-04. - 7 ARS-BFGL-NGS E-02. - 8 ARS-BFGL-NGS E-04. - 9 ARS-BFGL-NGS E-02. - 10 ARS-BFGL-NGS E-04. - 12 ARS-BFGL-NGS E-07. - 14 ARS-BFGL-NGS E-02. - 15 ARS-BFGL-NGS E-05. - 16 ARS-BFGL-NGS E-03. - 17 ARS-BFGL-NGS E-02. - 18 ARS-BFGL-NGS E-08. - 19 ARS-BFGL-NGS E-04. - 20 ARS-BFGL-NGS E-03. - 21 ARS-BFGL-NGS E-04. - 22 ARS-BFGL-NGS E-03. - Moreover, the presence of TRAF3, with a major role in class-switching of immunoglobulin, and XRCC3, with a role in DNA recombination and hypermutation in B cells, align with the isotype of the NAb that was mea- sured in in this study [31–34].. - The effect of antigen on B1 lymphocytes and NAb has been shown by the reduced level of IgG NAb, but not IgM, in germ-free antigen-free mice [40], however, the source of the antigenic signal has not yet been found. - Recently, the composition of gut microbiota was found to be correlated with the level of poly-reactive IgA in germ-free mice, but this correlation was caused by the genetic structure of the mice rather than gut microbiota [41]. - The absence of any significant SNPs with IgM, given the sample size of this study, is likely repre- senting the polygenetic control of the production of IgM.. - Immune re- sponse phenotypes used in this study were based on NAb of the isotypes, IgG and IgM, tested against the model antigen, not previously seen by cattle, keyhole limpet hemocyanin (KLH). - Four serial dilutions starting with 1/40 of the serum samples in wash buffer were added to the plate and incubated for 2 h at RT. - Plates were wash 5 times and the secondary antibodies conjugated to alkaline phosphatase dissolved in Tris-Tween buffer with 0.05% Tween 20 (pH 7.4) were added to the plates: either 1: 10.000 monoclonal anti-bovine IgG from mouse ascites fluid (Sigma-Aldrich, St. - Optical density values were cor- rected to the rolling mean of the positive controls for each plate to account for day and plate variation, as described by Heriazon et al. - The dilutions of the corrected OD values were summed and duplicates av- eraged for statistical analysis. - All experimental pro- cedures were approved by the Animal Care Commit- tee of the University of Guelph under guidelines of the Canadian Council of Animal Care.. - The association of the individual NAb with each indi- vidual SNP was estimated following a univariate mixed linear model:. - p , where p i is the allele fre- quency of the ith SNP and c ij is genotype of ith SNP of jth individual.. - λ is calculated as the median of the χ 2 test statistics. - Functional annotation of the positional candidate genes To identify the positional candidate genes that are asso- ciated with NAb, the genomic regions around the sig- nificant SNPs (FDR corrected p-value <. - These regions were cross-referenced against the cow genome (UMD 3.1, Ensemble Genes Release 91) using the BioMart tool in the Ensemble website to identify genes that are located in the vicinity of the significant SNPs. - NAb: Natural antibodies. - Mallard ’ s lab involved in the immune response sampling, Shannon Cartwright and Dr. - In addition, the list of proposed genes and their position that were found in this study are provided in the Table 3 in this manuscript.. - KTC optimized the NAb ELISA, collected serum samples and hair follicles, measured the NAb in serum samples and contributed to the drafting of the manuscript. - JP helped in the experimental design of this project. - All experimental procedures were approved by the Animal Care Committee of the University of Guelph under guidelines of the Canadian Council of Animal Care. - https://doi.org/10.1017/S . - https://doi.org/10.3168/jds.S . - https://doi.org/10.3168/jds.. - https://doi.org/10.1051/vetres:2003020.. - https://doi.org/10.1007/. - https://doi.org/10.1016/S . - Structure and Function of Natural Antibodies. - https://doi.org . - https://doi.org/10.1046/j x.. - https://doi.. - org/10.1016/S . - https://doi.org/10.3168/jds.2014-8818.. - Natural antibodies in bovine milk and blood plasma:. - doi.org/10.1016/J.VETIMM . - https://doi.org S1-S67.. - https://doi.org/10.. - Genetic variation of natural antibodies in milk of Dutch Holstein-Friesian cows. - https://doi.org/10.3168/jds.2010-3264.. - https://doi.org/10.3168/jds.2012-5919.. - https://doi.org/10.1093/nar/gkx1132.. - https://doi.org/10.3390/cancers4041180.. - https://doi.org/10.1093/nar/gkx1098.. - https://doi.org/10.1093/intimm/dxp013.. - https://doi.org/10.1016/j.saa . - https://doi.org/10.1016/j.jbiosc . - https://doi.org/10.1111/j.0006-341X x.. - https://doi.org/10.1007/s . - https://doi.org/10.1016/j.it.. - Natural antibodies bridge innate and adaptive immunity.. - https://doi.org/10.4049/jimmunol.1400844.. - https://doi.org/10.1002/eji . - https://doi.org/10.1016/j.immuni . - https://doi.org/10.1371/journal.pone.0131088.. - Genome-wide associations for natural antibodies in milk of Holstein-Friesians. - https://doi.org/10.1016/j.vaccine . - https://doi.org/10.1002/. - https://doi.org/10.1016/J.VETIMM . - https://doi.org/. - 10.3168/jds.2008-1758.. - https://doi.org/10.3168/JDS.2007-0980.. - https://doi.org/10.1038/ng.2876.. - https://doi.org/10.1093/nar/gks1147.
Xem thử không khả dụng, vui lòng xem tại trang nguồn hoặc xem
Tóm tắt