Genetic variation in humoral response to an Escherichia coli O157:H7 vaccine in beef cattle

Individuals often respond differently to the same vaccine; some of this variation may be caused by genetic differences among animals. Our objective was to estimate heritability and identify genomic regions associated with humoral response to an Escherichia coli O157:H7 vaccine in beef cattle. Crossbred beef cattle (n = 651) were vaccinated with a commercially available E. coli O157:H7 vaccine. Serum was collected at time of initial vaccination (d 0), booster (d 21), and d 56 after initial vaccination. Total antibodies specific to siderophore receptor and porin proteins in the vaccine were quantified by enzyme-linked immunosorbent assay. Genomic DNA was isolated from whole blood and genotyped with the bovine GeneSeek Genomic Profiler-High Density 78K or 26K Single Nucleotide Polymorphism BeadChip and imputed to 777,000 SNP genotypes. Heritability was estimated by restricted maximum likelihood (REML) using both 1) pedigree and 2) genomic relationships among individuals. Fixed effects were contemporary group, calf age, sex, principal components from SNP genotype data, and pedigree-derived heterozygosity effects. Additive and dominance effects of SNPs were estimated individually while accounting for contemporary group, sex, and the top 20 principal components calculated from the genomic relationship matrix. Heritability of initial response to vaccination (d 21 –d 0) was 0.10 ± 0.175 using pedigree relationships and 0.14 ± 0.149 using genomic relationships, but neither estimate was statistically different from zero. Heritability of booster (d 56 –d 21) and overall (d 56 –d 0) responses were low and not statistically significant from zero. There were no clusters of linked SNP associated with vaccine response, but eight regionally isolated SNPs were significantly associated with initial or overall response to vaccination. Regional genetic variation for initial response to an E. coli O157:H7 vaccine was observed, although overall heritability of this response was not statistically significant from zero.

不同个体对同一疫苗的应答往往存在差异，这类差异的部分成因可归结为动物间的遗传差异。本研究旨在估算肉牛对大肠杆菌O157:H7（Escherichia coli O157:H7）疫苗的体液免疫应答的遗传力，并筛选与之相关的基因组区域。本研究共纳入651头杂交肉牛，均接种市售大肠杆菌O157:H7疫苗。分别于初次免疫当天（第0天）、加强免疫当天（第21天）及初次免疫后第56天采集血清样本。采用酶联免疫吸附试验（enzyme-linked immunosorbent assay）定量检测疫苗中铁载体受体与孔蛋白特异性总抗体水平。从全血中提取基因组DNA，使用牛源GeneSeek基因组高密度分型78K或26K单核苷酸多态性（Single Nucleotide Polymorphism, SNP）芯片进行基因分型，并填充至777,000个SNP位点的基因型数据。分别采用1）个体间系谱亲缘关系、2）个体间基因组亲缘关系，通过约束最大似然法（restricted maximum likelihood, REML）估算遗传力。固定效应设置为同期组、犊牛日龄、性别、SNP基因型数据得到的主成分，以及系谱推导的杂合度效应。在校正同期组、性别及基于基因组亲缘关系矩阵计算得到的前20个主成分的前提下，分别估算SNP的加性效应与显性效应。基于系谱亲缘关系估算的初次免疫应答（第21天–第0天）遗传力为0.10 ± 0.175，基于基因组亲缘关系的估算值为0.14 ± 0.149，但两项估算值均与0无统计学差异。加强免疫应答（第56天–第21天）与整体免疫应答（第56天–第0天）的遗传力均较低，且与0无统计学差异。未发现与疫苗应答相关的连锁SNP簇，但有8个独立区域的SNP与初次免疫或整体免疫应答显著相关。尽管该免疫应答的整体遗传力未达到统计学显著性，但本研究仍观察到肉牛对大肠杆菌O157:H7疫苗的初次免疫应答存在区域遗传差异。