Yang Tongtong, Luo Hanpeng, Lou Wenqi, Chang Yao, Brito Luiz F, Zhang Hailiang, Ma Longgang, Hu Lirong, Wang Ao, Li Shanshan, Guo Gang, Wang Yachun
State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Laboratory of Animal Genetics, Breeding, and Reproduction, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
School of Life Sciences, Westlake University, Hangzhou, 310030, China.
J Dairy Sci. 2024 Jul;107(7):4772-4792. doi: 10.3168/jds.2023-24345. Epub 2024 Feb 29.
Hematological parameters refer to the assessment of changes in the number and distribution of blood cells, including leukocytes (LES), erythrocytes (ERS), and platelets (PLS), which are essential for the early diagnosis of hematological system disorders and other systemic diseases in livestock. In this context, the primary objectives of this study were to investigate the genomic background of 19 hematological parameters in Holstein cattle, focusing on LES, ERS, and PLS blood components. Genetic and phenotypic (co)variances of hematological parameters were calculated based on the average information restricted maximum likelihood method and 1,610 genotyped individuals and 5,499 hematological parameter records from 4,543 cows. Furthermore, we assessed the genetic relationship between these hematological parameters and other economically important traits in dairy cattle breeding programs. We also carried out genome-wide association studies and candidate gene analyses. Blood samples from 21 primiparous cows were used to identify candidate genes further through RNA sequencing (RNA-seq) analyses. Hematological parameters generally exhibited low-to-moderate heritabilities ranging from 0.01 to 0.29, with genetic correlations between them ranging from -0.88 ± 0.09 (between mononuclear cell ratio and lymphocyte cell ratio) to 0.99 ± 0.01 (between white blood cell count and granulocyte cell count). Furthermore, low-to-moderate approximate genetic correlations between hematological parameters with one longevity, 4 fertility, and 5 health traits were observed. One hundred ninety-nine significant SNP located primarily on the Bos taurus autosomes (BTA) BTA4, BTA6, and BTA8 were associated with 16 hematological parameters. Based on the RNA-seq analyses, 6,687 genes were significantly downregulated and 4,119 genes were upregulated when comparing 2 groups of cows with high and low phenotypic values. By integrating genome-wide association studies (GWAS), RNA-seq, and previously published results, the main candidate genes associated with hematological parameters in Holstein cattle were ACRBP, ADAMTS3, CANT1, CCM2L, CNN3, CPLANE1, GPAT3, GRIP2, PLAGL2, RTL6, SOX4, WDFY3, and ZNF614. Hematological parameters are heritable and moderately to highly genetically correlated among themselves. The large number of candidate genes identified based on GWAS and RNA-seq indicate the polygenic nature and complex genetic determinism of hematological parameters in Holstein cattle.
血液学参数是指对血细胞数量和分布变化的评估，包括白细胞（LES）、红细胞（ERS）和血小板（PLS），这些对于家畜血液系统疾病和其他全身性疾病的早期诊断至关重要。在此背景下，本研究的主要目标是调查荷斯坦奶牛19项血液学参数的基因组背景，重点关注LES、ERS和PLS血液成分。基于平均信息约束最大似然法以及来自4543头奶牛的1610个基因分型个体和5499条血液学参数记录，计算了血液学参数的遗传和表型（共）方差。此外，我们评估了这些血液学参数与奶牛育种计划中其他经济重要性状之间的遗传关系。我们还开展了全基因组关联研究和候选基因分析。使用来自21头初产奶牛的血样，通过RNA测序（RNA-seq）分析进一步鉴定候选基因。血液学参数的遗传力一般在0.01至0.29之间，呈低到中等水平，它们之间的遗传相关性在-0.88±0.09（单核细胞比例与淋巴细胞比例之间）至0.99±0.01（白细胞计数与粒细胞计数之间）之间。此外，观察到血液学参数与一个长寿、4个繁殖力和5个健康性状之间存在低到中等程度的近似遗传相关性。199个主要位于牛（Bos taurus）常染色体（BTA）BTA4、BTA6和BTA8上的显著单核苷酸多态性（SNP）与16项血液学参数相关。基于RNA-seq分析，在比较两组具有高和低表型值的奶牛时，6687个基因显著下调，4119个基因上调。通过整合全基因组关联研究（GWAS）、RNA-seq和先前发表的结果，与荷斯坦奶牛血液学参数相关的主要候选基因有ACRBP、ADAMTS3、CANT1、CCM2L、CNN3、CPLANE1、GPAT3、GRIP2、PLAGL2、RTL6、SOX4、WDFY3和ZNF614。血液学参数具有遗传性，且彼此之间存在中等至高度的遗传相关性。基于GWAS和RNA-seq鉴定出的大量候选基因表明荷斯坦奶牛血液学参数具有多基因性质和复杂的遗传决定性。
