Sharma B S, Leyva I, Schenkel F, Karrow N A
Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, N1G 2W1, Canada.
J Dairy Sci. 2006 Sep;89(9):3626-35. doi: 10.3168/jds.S0022-0302(06)72402-X.
Mastitis, an inflammatory disease of the mammary gland generally caused by intramammary infections, is the most frequently occurring disease in the North American dairy industry. Reduced milk yield, milk quality, and lactation persistency as well as early culling contribute to the economic losses associated with this disease. During intramammary infections, cells of the innate immune system become activated through pattern recognition receptors that recognize conserved molecular signatures associated with the invading pathogen. The quality, timing, and intensity of the host inflammatory and subsequent immune response determine the fate of this disease. Toll-like receptor 4 (TLR4) is an important pattern recognition receptor that recognizes endotoxins associated with gram-negative bacterial infections. Its role in pathogen recognition and subsequent initiation of the inflammatory and immune response makes it a suitable candidate gene for enhancing disease resistance in Canadian Holsteins. In this study, polymorphisms in the TLR4 gene were identified in the Canadian Holstein bull population. Genotypes and haplotypes were constructed, and their associations with somatic cell score and lactation persistency were determined. Sequencing of selective DNA pools was used to reveal polymorphisms in TLR4. Two DNA pools were constituted based on high and low estimated breeding values for somatic cell scores. A total of 3 single nucleotide polymorphisms (SNP), including 1 SNP in a putative promoter region (P-226) and 2 SNP in exon3 (E3+1656 and E3+2021) of TLR4 were detected. A total of 388 bulls were genotyped for the SNP, haplotypes were reconstructed, and their frequencies were obtained. Polymorphisms in these regions were found to be associated with estimated breeding values for lactation persistency, and somatic cell scores in the Canadian Holstein bull population. The unfavorable alleles at P-226 and E3+1656 were found at a frequency of 40 and 37%, respectively; hence, selection against these alleles is promising in Canadian Holsteins. Selection against the unfavorable allele, T at E3+2021, is limited because of its low frequency (7%). Two frequently occurring haplotypes (GCC and CTC) occurred in 86% of the Canadian Holstein bull population chosen for genotyping. The most frequent haplotype (GCC; 54%) was found to be associated with higher lactation persistency and lower somatic cell scores. The transversion SNP in the putative promoter region (P-226) was in a potential DNA binding site.
乳腺炎是一种通常由乳腺内感染引起的乳腺炎症性疾病，是北美奶牛业中最常发生的疾病。产奶量、牛奶品质和泌乳持续性的降低以及过早淘汰导致了与这种疾病相关的经济损失。在乳腺内感染期间，先天性免疫系统的细胞通过模式识别受体被激活，这些受体识别与入侵病原体相关的保守分子特征。宿主炎症反应及后续免疫反应的质量、时机和强度决定了这种疾病的转归。Toll样受体4（TLR4）是一种重要的模式识别受体，可识别与革兰氏阴性菌感染相关的内毒素。其在病原体识别以及随后引发炎症和免疫反应中的作用使其成为增强加拿大荷斯坦奶牛抗病能力的合适候选基因。在本研究中，在加拿大荷斯坦公牛群体中鉴定了TLR4基因的多态性。构建了基因型和单倍型，并确定了它们与体细胞评分和泌乳持续性的关联。使用选择性DNA池测序来揭示TLR4中的多态性。基于体细胞评分的高低估计育种值构建了两个DNA池。共检测到3个单核苷酸多态性（SNP），包括TLR4假定启动子区域中的1个SNP（P - 226）和外显子3中的2个SNP（E3 + 1656和E3 + 2021）。对388头公牛进行了SNP基因分型，重建了单倍型并获得了它们的频率。发现这些区域的多态性与加拿大荷斯坦公牛群体中的泌乳持续性估计育种值和体细胞评分相关。在P - 226和E3 + 1656处的不利等位基因频率分别为40%和37%；因此，在加拿大荷斯坦奶牛中针对这些等位基因进行选择是有前景的。由于E3 + 2021处不利等位基因T的频率较低（7%），针对它的选择受到限制。在选择进行基因分型的加拿大荷斯坦公牛群体中，86%出现了两种常见的单倍型（GCC和CTC）。发现最常见的单倍型（GCC；54%）与较高的泌乳持续性和较低的体细胞评分相关。假定启动子区域中的转换SNP（P - 226）位于一个潜在的DNA结合位点。
