Institute of Animal Breeding and Genetics, Justus-Liebig-University Gießen, Ludwigstr. 21b, 35390, Giessen, Germany.
Genet Sel Evol. 2019 Feb 6;51(1):4. doi: 10.1186/s12711-018-0444-4.
Body weight (BW) at different ages are of increasing importance in dairy cattle breeding schemes, because of their strong correlation with energy efficiency traits, and their impact on cow health, longevity and farm economy. In total, 15,921 dairy cattle from 56 large-scale test-herds with BW records were genotyped for 45,613 single nucleotide polymorphisms (SNPs). This dataset was used for genome-wide association studies (GWAS), in order to localize potential candidate genes for direct and maternal genetic effects on BW recorded at birth (BW0), at 2 to 3 months of age (BW23), and at 13 to 14 months of age (BW1314).
The first 20 principal components (PC) of the genomic relationship matrix ([Formula: see text]) grouped the genotyped cattle into three clusters. In the statistical models used for GWAS, correction for population structure was done by including polygenic effects with various genetic similarity matrices, such as the pedigree-based relationship matrix ([Formula: see text]), the [Formula: see text]-matrix, the reduced [Formula: see text]-matrix LOCO (i.e. exclusion of the chromosome on which the candidate SNP is located), and LOCO plus chromosome-wide PC. Inflation factors for direct genetic effects using [Formula: see text] and LOCO were larger than 1.17. For [Formula: see text] and LOCO plus chromosome-wide PC, inflation factors were very close to 1.0. According to Bonferroni correction, ten, two and seven significant SNPs were detected for the direct genetic effect on BW0, BW23, and BW1314, respectively. Seventy-six candidate genes contributed to direct genetic effects on BW with four involved in growth and developmental processes: FGF6, FGF23, TNNT3, and OMD. For maternal genetic effects on BW0, only three significant SNPs (according to Bonferroni correction), and four potential candidate genes, were identified. The most significant SNP on chromosome 19 explained only 0.14% of the maternal de-regressed proof variance for BW0.
For correction of population structure in GWAS, we suggest a statistical model that considers LOCO plus chromosome-wide PC. Regarding direct genetic effects, several SNPs had a significant effect on BW at different ages, and only two SNPs on chromosome 5 had a significant effect on all three BW traits. Thus, different potential candidate genes regulate BW at different ages. Maternal genetic effects followed an infinitesimal model.
在奶牛养殖计划中，不同年龄的体重（BW）变得越来越重要，因为它们与能量效率性状密切相关，并且对奶牛的健康、寿命和农场经济有影响。总共对来自 56 个大型测试群的 15921 头奶牛进行了体重记录的 45613 个单核苷酸多态性（SNP）的基因分型。该数据集用于全基因组关联研究（GWAS），以便定位直接遗传效应和母系遗传效应对出生时（BW0）、2-3 月龄（BW23）和 13-14 月龄（BW1314）记录的 BW 的潜在候选基因。
基因组关系矩阵的前 20 个主成分（PC）（[Formula: see text]）将基因分型的牛分为三组。在用于 GWAS 的统计模型中，通过包括多基因效应和各种遗传相似性矩阵（如基于系谱的关系矩阵[Formula: see text]、[Formula: see text]-矩阵、简化的[Formula: see text]-矩阵 LOCO（即排除候选 SNP 所在的染色体）和 LOCO 加染色体-wide PC）来校正群体结构。使用 [Formula: see text] 和 LOCO 的直接遗传效应的膨胀因子大于 1.17。对于 [Formula: see text] 和 LOCO 加染色体-wide PC，膨胀因子非常接近 1.0。根据 Bonferroni 校正，分别检测到直接遗传效应对 BW0、BW23 和 BW1314 的 10、2 和 7 个显著 SNP。76 个候选基因对 BW 的直接遗传效应有贡献，其中 4 个基因参与生长和发育过程：FGF6、FGF23、TNNT3 和 OMD。对于母系遗传效应对 BW0，仅鉴定到三个显著 SNP（根据 Bonferroni 校正）和四个潜在候选基因。第 19 号染色体上最显著的 SNP 仅解释了 BW0 的母体去回归证明方差的 0.14%。
对于 GWAS 中的群体结构校正，我们建议使用考虑 LOCO 加染色体-wide PC 的统计模型。关于直接遗传效应，几个 SNP 对不同年龄的 BW 有显著影响，只有 5 号染色体上的两个 SNP 对所有三个 BW 性状有显著影响。因此，不同的潜在候选基因调节不同年龄的 BW。母系遗传效应遵循微小模型。
