Genome-Wide Association Studies Reveal Susceptibility Loci for Noninfectious Claw Lesions in Holstein Dairy Cattle.
Genome-Wide Association Studies Reveal Susceptibility Loci for Noninfectious Claw Lesions in Holstein Dairy Cattle.
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DOI：
10.3389/fgene.2021.657375
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发表时间：
2021
影响因子：
3.7
通讯作者：
Oberbauer AM
中科院分区：
文献类型：
--
作者：
Lai E;Danner AL;Famula TR;Oberbauer AM
足底溃疡（SU）和白色线病（WLD）是两种常见的非感染性爪病变（NICL），由于角生产受损而引起，是奶牛跛行的常见原因，引起福利和盈利能力问题。SU和WLD易感性的低至中等遗传力估计表明，遗传选择可以降低其患病率。为了确定SU、WLD、SU和/或WLD以及任何类型的非感染性爪病变的易感基因座，使用广义线性混合模型（GLMM）回归、基于组块的关联检验（CBAT）和随机森林（RF）方法进行全基因组关联研究（GWAS）。将来自加州5个商业奶牛场的奶牛分类为无跛行记录且≥6岁的对照组（n = 102）或患有SU（n = 152）、WLD（n = 117）、SU和/或WLD（SU + WLD，n = 198）或任何类型的非感染性爪病变的病例（n = 217）。最高单核苷酸多态性（SNP）定义为在GLMM分析中通过Bonferroni校正的提示性和显著性阈值的SNP或经验证的RF模型认为重要的SNP。使用贝叶斯估计来量化最高SNP的影响。连锁不平衡（LD）块定义的最高单核苷酸多态性的候选基因和以前确定的，功能相关的数量性状基因座进行了探索。GLMM和CBAT方法揭示了与WLD、SU + WLD和NICL共同的SU和BTA 13在BTA 8上的相同关联区域。这些SNP具有与零显著不同的效应，并且他们定义的LD区块解释了每个数据集的显著量的表型方差（6.1- 8.1%，p < 0.05），表明这些区域对易感性的贡献很小但很显著。这些区域包含参与伤口愈合、皮肤损伤、骨生长和矿化、脂肪组织和角化的候选基因。对于SU，由BTA 8上最显著的SNP定义的LD阻断包括先前与SU相关的SNP。RF模型被过度拟合，表明SNP效应非常小，从而阻止了对SNP和任何下游分析的有意义的解释。这些发现表明，与各种生理系统相关的变异可能有助于NICL的易感性，证明了遗传易感性的复杂性。
Sole ulcers (SUs) and white line disease (WLD) are two common noninfectious claw lesions (NICL) that arise due to a compromised horn production and are frequent causes of lameness in dairy cattle, imposing welfare and profitability concerns. Low to moderate heritability estimates of SU and WLD susceptibility indicate that genetic selection could reduce their prevalence. To identify the susceptibility loci for SU, WLD, SU and/or WLD, and any type of noninfectious claw lesion, genome-wide association studies (GWAS) were performed using generalized linear mixed model (GLMM) regression, chunk-based association testing (CBAT), and a random forest (RF) approach. Cows from five commercial dairies in California were classified as controls having no lameness records and ≥6 years old (n = 102) or cases having SU (n = 152), WLD (n = 117), SU and/or WLD (SU + WLD, n = 198), or any type of noninfectious claw lesion (n = 217). The top single nucleotide polymorphisms (SNPs) were defined as those passing the Bonferroni-corrected suggestive and significance thresholds in the GLMM analysis or those that a validated RF model considered important. Effects of the top SNPs were quantified using Bayesian estimation. Linkage disequilibrium (LD) blocks defined by the top SNPs were explored for candidate genes and previously identified, functionally relevant quantitative trait loci. The GLMM and CBAT approaches revealed the same regions of association on BTA8 for SU and BTA13 common to WLD, SU + WLD, and NICL. These SNPs had effects significantly different from zero, and the LD blocks they defined explained a significant amount of phenotypic variance for each dataset (6.1–8.1%, p < 0.05), indicating the small but notable contribution of these regions to susceptibility. These regions contained candidate genes involved in wound healing, skin lesions, bone growth and mineralization, adipose tissue, and keratinization. The LD block defined by the most significant SNP on BTA8 for SU included a SNP previously associated with SU. The RF models were overfitted, indicating that the SNP effects were very small, thereby preventing meaningful interpretation of SNPs and any downstream analyses. These findings suggested that variants associated with various physiological systems may contribute to susceptibility for NICL, demonstrating the complexity of genetic predisposition.
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