我国部分地区奶牛乳腺炎流行病学调查及IRAK2基因与乳腺炎相关性分析
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摘要
奶牛乳腺炎是危害奶牛业的重大疾病之一，分为临床型乳腺炎和隐性乳腺炎，临床型乳腺炎大多是由病原菌引起，可依据常规诊断方法做出诊断，隐性乳腺炎依据常规诊断方法很难做出判断，同时，由于其对奶牛业造成的损失巨大，因此对规模化奶牛养殖场乳腺炎特别是隐性乳腺炎流行病学调查至关重要。而对患隐性乳腺炎奶牛的判定，目前国际上常用的方法是根据牛奶中体细胞数经过校正后的牛奶体细胞评分（SCS）来确定，SCS<5为正常健康牛，SCS>5为感染乳腺炎的患病牛。隐性乳腺炎与多种因素有关，遗传是其中一个因素，在相同环境与管理条件下，奶牛个体对乳腺炎的易感性存在着较大的差异。从遗传角度来讲，抗奶牛乳腺炎基因有很多，而IRAK及其受体是已发现的乳腺炎抗性基因之一，共有4个家族成员，其中IRAK2是TLRs信号转导通路上的信号分子之一。本研究以我国天津、济南、青岛、东营的10个规模化中国荷斯坦奶牛养殖场共1361头泌乳期奶牛作为研究对象，以常规诊断方法作为临床型乳腺炎的判定标准和以SCS作为隐性乳腺炎判定标准进行流行病学调查，并以乳腺炎抗性相关基因IRAK2作为候选基因，研究其与泌乳性状及体细胞评分之间的相关性，并探讨建立基因分型检测方法的可行性，为我国规模化奶牛养殖场牛群乳腺炎流行情况提供理论数据和在实践中从奶牛自身乳腺炎抗性方面防治该病提供参考依据。
在所研究的奶牛群体中，检测出临床型乳腺炎发病率为2.87%，主要致病菌为金黄色葡萄球菌、停乳链球菌、无乳链球菌、大肠杆菌，隐性乳腺炎阳性率为50.53%。经χ~2检验，乳腺炎发病率在5-6月、7-8月、9-10月分别与1-2月间差异显著，在第2-6胎分别与第1胎之间阳性率差异极显著。
与中国荷斯坦牛泌乳性能的关联分析表明，乳腺炎抗性基因IRAK2位点g.40035基因型TT个体的乳蛋白率高于TC基因型个体（P<0.05）；位点g.40120纯合子CC基因型个体的乳脂率大于杂合子TC基因型个体（P<0.05）。与体细胞评分相关性分析表明，g.28879位点的CC基因型个体体细胞评分显著低于CT基因型个体（P<0.05），且以加性效应为主；位点g.28916的GG基因型个体显著低于AG基因型个体（P<0.05）。共检测到30个单倍型和71种单倍型组合，与SCS相关性分析表明，H21H23（TTAGGCTCCC）单倍型组合个体体细胞评分最低，H7H27（CTAGGGTCCC）单倍型组合个体体细胞评分最高。
采用PCR-SSCP方法检测到IRAK2基因第7外显子出现三种不同带型，并用PCR-RFLPs方法，经RsaI内切酶对PCR产物进行酶切后也出现三种不同的带型，这与NCBI报道一致，为采用PCR-SSCP联合酶切方法建立IRAK2基因分型检测方法的可行性提供理论参考。
Dairy cows mastitis is one of the major diseases of dairy farming, includingclinical mastitis and subclinical mastitis. The former mastitis is caused by pathogens,which will be diagnosed on the basis of routine diagnostic method. While the latermastitis is very difficult to determine according to routine method, which result inhuge economic loss. So it is important of epidemiology investigation of bovinemastitis to the scale dairy farms especially subclinical mastitis. The somatic cellcount(SCC) is the most commonly method to determine the disease. In order to makethe SCC statistical analysis to application of the normal distribution, it will beconverted to SCC somatic cell score (SCS), when SCS<5means healthy, SCS>5means infection. Dairy cow mastitis is contributed to many factor, the genetic is oneof them. The aflectivity of individual milk cow discovered significant difference evenunder the same conditions. There are many candidate genes, the IRAK and itsreceptors have been found one of mastitis resistance genes so far. It has4familymembers, and the IRAK2is TLRs signal transduction pathway on signal molecules.
In this thesis,1361cows from10large-scale China Holstein cows farming inTianjin, Ji'nan, Qingdao, and Dongying were investigated the epidemiology by takingthe routine diagnostic method as the criterion of clinical mastitis and subclinicalmastitis by SCS as criterion. We also took IRAK2as candidate gene, investigating therelativity between milkcharacter and evaluation of somatic cells, discussed thefeasibility of Genotyping method. The theoretical data of the epidemic situation wastaken for large-scale dairy farm cattle and providing references to control the diseaseof cow's mastitis resistance in dairy production.
In our study, the clinical mastitis incidence rate was2.87%, the main pathogenswere Staphylococci, S. dysgalactiae, S. agalactiae and Bacillus coli, and the positiverate of subclinical mastitis was50.53%. The difference of mastitic incidence wasobserved between5-6months,7-8months,9-10months respectively with1-2months,while marked difference in the positive rate between the firstborn and second tosixborn according to χ~2test.
It is shown by genetic polymorphisms of IRAK2and its correlation with milkperformance traits in Chinese Holsteins that in the g.40035loci, the cows withgenotype TT showed higher protein rate than those with genotypes TC(P<0.05), in theg.40120loci, the cows with genotype CC showed higher fat rate than those withgenotypes TC(P<0.05). Statistical analyses by genetic polymorphism of IRAK2geneand its associations with mastitis in dairy cattle revealed significant associations between genotype CC and CT in position g.28879, and between GG and AG inposition g.28916. The SCS value of genotype CC and GG was lower than that of CTand AG, respectively (P<0.05). The results of haplotype analysis of five SNPs showedthat30different haplotypes and71haplotype combinations were identified. The valueof SCS of individuals with H21H23(TTAGGCTCCC) was the lowest and theH7H27(CTAGGGTCCC) was the highest through the result of association betweenpolymorphisms of IRAK-2gene and SCS.
Three genotypes were obtained by PCR-SSCP in excon7in IRAK2gene and thesame genotypes is appeared by using PCR-RFLPs and digesting to the PCRproduction by RsaI, which consistent with NCBI. It may be used as a possibleGenotyping method for the IRAK2gene of mastitis resistance in dairy cattle byPCR-SSCP and digest with restriction endonuclease.
在所研究的奶牛群体中，检测出临床型乳腺炎发病率为2.87%，主要致病菌为金黄色葡萄球菌、停乳链球菌、无乳链球菌、大肠杆菌，隐性乳腺炎阳性率为50.53%。经χ~2检验，乳腺炎发病率在5-6月、7-8月、9-10月分别与1-2月间差异显著，在第2-6胎分别与第1胎之间阳性率差异极显著。
与中国荷斯坦牛泌乳性能的关联分析表明，乳腺炎抗性基因IRAK2位点g.40035基因型TT个体的乳蛋白率高于TC基因型个体（P<0.05）；位点g.40120纯合子CC基因型个体的乳脂率大于杂合子TC基因型个体（P<0.05）。与体细胞评分相关性分析表明，g.28879位点的CC基因型个体体细胞评分显著低于CT基因型个体（P<0.05），且以加性效应为主；位点g.28916的GG基因型个体显著低于AG基因型个体（P<0.05）。共检测到30个单倍型和71种单倍型组合，与SCS相关性分析表明，H21H23（TTAGGCTCCC）单倍型组合个体体细胞评分最低，H7H27（CTAGGGTCCC）单倍型组合个体体细胞评分最高。
采用PCR-SSCP方法检测到IRAK2基因第7外显子出现三种不同带型，并用PCR-RFLPs方法，经RsaI内切酶对PCR产物进行酶切后也出现三种不同的带型，这与NCBI报道一致，为采用PCR-SSCP联合酶切方法建立IRAK2基因分型检测方法的可行性提供理论参考。
Dairy cows mastitis is one of the major diseases of dairy farming, includingclinical mastitis and subclinical mastitis. The former mastitis is caused by pathogens,which will be diagnosed on the basis of routine diagnostic method. While the latermastitis is very difficult to determine according to routine method, which result inhuge economic loss. So it is important of epidemiology investigation of bovinemastitis to the scale dairy farms especially subclinical mastitis. The somatic cellcount(SCC) is the most commonly method to determine the disease. In order to makethe SCC statistical analysis to application of the normal distribution, it will beconverted to SCC somatic cell score (SCS), when SCS<5means healthy, SCS>5means infection. Dairy cow mastitis is contributed to many factor, the genetic is oneof them. The aflectivity of individual milk cow discovered significant difference evenunder the same conditions. There are many candidate genes, the IRAK and itsreceptors have been found one of mastitis resistance genes so far. It has4familymembers, and the IRAK2is TLRs signal transduction pathway on signal molecules.
In this thesis,1361cows from10large-scale China Holstein cows farming inTianjin, Ji'nan, Qingdao, and Dongying were investigated the epidemiology by takingthe routine diagnostic method as the criterion of clinical mastitis and subclinicalmastitis by SCS as criterion. We also took IRAK2as candidate gene, investigating therelativity between milkcharacter and evaluation of somatic cells, discussed thefeasibility of Genotyping method. The theoretical data of the epidemic situation wastaken for large-scale dairy farm cattle and providing references to control the diseaseof cow's mastitis resistance in dairy production.
In our study, the clinical mastitis incidence rate was2.87%, the main pathogenswere Staphylococci, S. dysgalactiae, S. agalactiae and Bacillus coli, and the positiverate of subclinical mastitis was50.53%. The difference of mastitic incidence wasobserved between5-6months,7-8months,9-10months respectively with1-2months,while marked difference in the positive rate between the firstborn and second tosixborn according to χ~2test.
It is shown by genetic polymorphisms of IRAK2and its correlation with milkperformance traits in Chinese Holsteins that in the g.40035loci, the cows withgenotype TT showed higher protein rate than those with genotypes TC(P<0.05), in theg.40120loci, the cows with genotype CC showed higher fat rate than those withgenotypes TC(P<0.05). Statistical analyses by genetic polymorphism of IRAK2geneand its associations with mastitis in dairy cattle revealed significant associations between genotype CC and CT in position g.28879, and between GG and AG inposition g.28916. The SCS value of genotype CC and GG was lower than that of CTand AG, respectively (P<0.05). The results of haplotype analysis of five SNPs showedthat30different haplotypes and71haplotype combinations were identified. The valueof SCS of individuals with H21H23(TTAGGCTCCC) was the lowest and theH7H27(CTAGGGTCCC) was the highest through the result of association betweenpolymorphisms of IRAK-2gene and SCS.
Three genotypes were obtained by PCR-SSCP in excon7in IRAK2gene and thesame genotypes is appeared by using PCR-RFLPs and digesting to the PCRproduction by RsaI, which consistent with NCBI. It may be used as a possibleGenotyping method for the IRAK2gene of mastitis resistance in dairy cattle byPCR-SSCP and digest with restriction endonuclease.
引文
[1]杨钦,王长法,杨宏军,等.牛乳中金黄色葡萄球菌山东分离株（zfb）β-溶血素(hlb)的克隆、表达及溶血活性分析[J].中国农业科学,2009,42(1):324-330.
[2]尹荣兰,王浩然,张艳晶,等.奶牛乳腺炎金黄色葡萄球菌CIFA核酸疫苗的构建及免疫原性试验[J].中国兽医学报,2012,32(4):439-542.
[3]王桂琴.奶牛乳腺炎的病因及防治[J].上海畜牧兽医通讯,2005,5:56-57.
[4] Harmon R J. Symposium: Mastitis and genetic evaluation for somatic cell count:Physiology of mastitis and factors affecting somatic cell counts[J]. Dairy Sci,1994,77(7):2103-2112.
[5]王会珍.奶牛乳房炎的危害及分类[J].山东省农业管理干部学院学报,2007,23(4):151-152.
[6]蒋春茂,周新民,周广生,等．奶牛乳房炎研究进展[J].中国畜牧兽医,2004(5):36-38．
[7]严作廷,王东升,王旭荣,等.我国奶牛主要疾病研究进展[J].中国草食动物2011,31(6):69-72.
[8]刘新勃,田国宁.潍坊地区奶牛隐性乳腺炎感染率调查及防治效果考核[J].中国动物检疫,2006,23(1):41-42.
[9]胡建春.不同饲养环境下奶牛隐性乳腺炎流行病学调查[J].当代畜牧,2005,34(2):19-21.
[10]易本驰.奶牛隐性乳腺炎调查及病原分离鉴定[J].上海畜牧兽医通讯,2007,1:221.
[11]赵香汝,李寸欣,郑雪花,等.张家口地区奶牛隐性乳腺炎的流行特点[J].中国动物检疫,2010,27(1):52-53.
[12]吕润全,刘文杰,郭伟.南京地区奶牛隐性乳腺炎的调查与分析[J].江苏农业科学,2010,2:234-235.
[13]李宏胜,郁杰.奶牛乳房炎病原菌人工诱发奶山羊急性乳房炎试验[J].动物医学进展,2004,25(4):84-87.
[14]许毅.奶牛乳房炎发病原因综述[J].饲料广角,2003,21:38-40.
[15]刘锡武,马保臣.奶牛乳腺炎的调查报告[J].兽药与饲料添加剂,2004,9(2):27-28．
[16]王成,童洁,高东.奶牛隐性乳房炎的检测与治疗效果观察[J].畜牧与兽医1998,30(3):123-124.
[17]王海军,王赞江.奶牛乳房炎的病因及综合防治[J].2006,32(5):101-104.
[18]李宗方,董喜林,叶东东等.荷斯坦牛与新疆褐牛牛奶体细胞数对比分析[J].新疆农业科学,2009,46(6):1336-1340.
[19]王希春,李培,吴金节.奶牛隐性乳房炎对牛奶中体细胞数及品质的影响[J].中国奶牛,2008,4:49-51.
[20]赵兴,徐新明,邓江玲,等.奶牛乳中体细胞数与产奶性状的相关分析[J].草食家畜,2011,152(3):21-23.
[21]周亚平,刘琴,施开平,等.乳体细胞数与产奶量、乳成分的关系研究[J].中国奶牛,2011,4:40-42.
[22]周木清,金尔光,周世同,等. DHI报告在奶牛饲养管理中的分析与应用[J].现代农业科技,2006,9:65-68.
[23] KOLDWIJE，EMANUWLSONU. Relation of milk Production loss to milksomatic cell count[J]. ACAT vet Scand,1999,40:47-56.
[24]屈常林,王怀娜,蓝响.牛奶体细胞数及牛乳中酶活性与隐性乳腺炎致病菌之间的相关性[J].中国奶牛,2010,3:39-41.
[25] H.Dosogne, F.Vangroenweghe, J.Mehrzad. et al. Differential leukocyte countmethod for bovine low somatic cell count milk[J]. Journal of Dairy Science2003,86(3):828-834.
[26]王芳,胡松华.体细胞含量与牛奶质量的关系[J].中国奶牛,2005,(4):51-52.
[27]张慧林,余文文,刘小林,等.牛乳中体细胞数与产奶量和乳成分的相关分析[J].西北农业学报,2010,1(4):1-4.
[28]郝建国.日本学者对体细胞数与乳房炎关系的论述[J].中国奶牛,2002,1:52-54.
[29]陈华林.体细胞数在奶牛乳房卫生保健工作中的应用[J].中国奶牛,2000,6:49-51.
[30]麻士卫,陈永福,王记成,等.牛乳体细胞数与乳蛋白含量相关性的研究[J].中国乳品工业,2006,34(6):27-31.
[31] Shamay A，Shapiro F，Mabjeesh SJ，et al. Casein-derived phosphopeptidesdisrupt tight junction integrity, and precipitously dry up milk secretion in goats[J]. Life sciences,2002,70(23):2707-2719.
[32]刘文娇,孙少华.线性模型对影响奶牛产奶性能的主要相关因素分析[J].中国奶牛,2010,6:24-26.
[33]程广龙,江喜春,赵辉玲,等.牛奶中高体细胞数的危害及调控措施畜牧与饲料科学[J].2009,30(4):65-66.
[34] Ma Y, Ryan C. Effects of somatic cell count on quality and shelf-life ofpasteurized fluid milk[J]. J Dairy Sci,2000,83:264-274.
[35]储明星,石万海,邝霞,等.浅谈奶牛乳房炎[J].中国奶牛,2001(3):39-40.
[36]邢慧敏,云振宇,李妍,等.牛乳体细胞数与乳中离子含量相关性的研究[J].食品科学2007,28(5)53:53-56.
[37]叶纪梅,王加启,赵国琦.细胞数过高对乳制品品质的影响[J].中国奶牛,2006,5:41-44.
[38] Da Y, Grossman M, Misztal I, et al. Estimation of genetic parameters for somaticcell score in Holsteins[J]. Journal of Dairy Science,1992,75(8):2265-2271.
[39] Mark T, Fikse W F, Emanuelson U, et al. International genetic evaluations ofHolstein sires for milk somatic cell and clinical mastitis[J]. Journal of DairyScience,2002,85(9):2384-2392.
[40] Schutz M M. Genetic evaluation of somatic cell scores for United States dairycattle[J]. Journal of Dairy Science,1994,77(7):2113-2129.
[41] SHOOK G E. Approaches to summarizing somatic cell counts which improveinterpretability[M]. Proc. Natl. Mastitis Countil, Arlington,1982, VA:150-166.
[42]李建斌,孙少华,田雨泽.中国荷斯坦牛乳中体细胞数变化规律的研究[J].新疆农业科学,2009,46(6):1336-1340.
[43]郑怀军,张永根,杨贵,等.对通过DHI改进奶牛场生产管理的观察与分析[J].中国奶牛,2006(5):24-27.
[44]毛永江,杨章平.南方地区中国荷斯坦牛乳中体细胞数变化规律的研究[J].中国奶牛,2007年会论文集·159-161.
[45]李世平,毛永江,常洪,等.南方地区中国荷斯坦牛乳中体细胞数变化规律的研究[J].中国畜牧杂志,2008,44(3):7-9.
[46]赵连生,王加启,郑楠,等.牛奶质量安全主要风险因子分析Ⅶ.体细胞数和菌落总数[J].中国畜牧兽医,2012,39(7):1-5.
[47]刘岩,王艳鸽,张鑫.食品中抗生素检测技术研究进展[J].山西食品工业,2005,3:38-41,43.
[48] Heringstad B, Klemetsdal q Ruane G. Responses to selection against clinicalmastitis in the Norwegian cattle population[J]. Anim Sci,2001,51:155-165.
[49] Rachel Didier Boichard. Genetics of resisitance to mastitis in dairy cattle[J]. Vet.Res.,2003,34:671-688.
[50] Heringstad, B., Klemetsdal, G., Ruane, J. Clinical mastitis in Norwegian cattle:frequency, variance components, and genetic correlation with protein yield[J].Dairy Sci,1999,82:1325-1330.
[51] T. Mark,W.F. Fikse, U. Emanuelson, et al. International Genetic Evaluations ofHolstein Sires for Milk Somatic Cell and Clinical Mastitis[J]. Journal of DairyScience,2002,85(9):2384-2392.
[52] R.A Mrode, G.J.T Swanson. Estimation of genetic parameters for somatic cellcount in the first three lactations using random regression[J]. LivestockProduction Science,2003,79(2–3):239-247.
[53]高树新. BoLA基因多态性及其与奶牛乳腺炎的关联研究[D].内蒙古农业大学博士学位论文,2005.
[54]张才骏.遗传因素在牛产科疾病中的作用[J].国外兽医学-畜禽疾病,1991,2:1-5.
[55] J Harmon, R.J., Physiology of mastitis and factors affecting somatic cellcounts[J]. Dairy Sci,1994,77:2103-2112.
[56] J.I. Weller, A. Saran, Y. Zeliger. Genetic and environmental relationships amongsomatic cell count, bacterial infection, and clinical mastitis[J]. Journal of DairyScience,1992,75(9:2532-2540.
[57] Johann C., Detilleux, et al. David H. Kelley. Mastitis of periparturient Holsteincattle: a phenotypic and genetic study[J]. Journal of Dairy Science1995,78(10):2285-2293.
[58] Nash DL, Rogers GW, Cooper JB, et al. Heritability of clinical mastitis incidenceand relationships with sire transmitting abilities for somatic cell score, udder typetraits, productive life, and protein yield[J]. J Dairy Sci.2000,83(10):2350-2360.
[59] J. P s, E.A. M ntysaari. Relationships Between Clinical Mastitis, Somatic CellScore, and Production for the First Three Lactations of Finnish Ayrshire[J].Journal of Dairy Science1996,79(7):1284-1291.
[60] T Mark, WF Fikse, U Emanuelson, et al. International genetic evaluations ofHolstein sires for milk somatic cell and clinical mastitis[J]. Journal of dairyscience, Journal of Dairy Science,2002,85(9):2384-2392.
[61] Shook GE, Schutz MM. Selection on somatic cell score to improve resistance tomastitis in the United States[J]. J Dairy Sci.1994,77(2):648-58.
[62] Banos G, Shook G E. Genotype by environment interaction and geneticcorrelations among parities for somatic cell count and milk yield[J]. Journal ofDairy Science,1990,73(9):2563-2573.
[63] Lund T, Miglior F, Dekkers J C M, et al. Genetic relationships between clinicalmastitis, somatic cell count, and udder conformation in Danish Holsteins[J].Livestock Production Science,1994,39(3):243-251.
[64] Fallin D, Cohen A, Essioux L, et al. Genetic analysis of case/control data usingEstimated Haplotype Frequencies: Application to APOE locus variation andAlzheimer’s disease[J]. Genome Research,2001,11(1):143-151.
[65]肖正中,赖松家.奶牛分子育种的研究进展[J].畜牧与兽医,2003,35(6):41-44.
[66]魏伟,苗永旺.奶牛乳腺炎抗性候选基因多态性研究进展[J].中国牛业科学2011,37(6):49-51,56.
[67] Wojdak-Maksymiec K, Kmie M, Zukiewicz A. Associations between defensinpolymorphism and somatic cell count in milk and milk utility traits in Jerseydairy cows. Journal of Veterinary Medicine Series A-Physiology Pathology[J].Clinical Medicine,2006,53(10):495-500.
[68] Schwerin M, Kühn C, Brunner R, et al. QTL mapping and mining functionalcandidate genes affecting health-the German ADR QTL Dairy Cattle Project[J].Animal Science Papers and Reports,2004,22(1),95-100.
[69] Vilkki H.J., Dekoning D.I., BinK, et al. Multiple marker mapping of quantitativetrait loci of Finnish diary cattle by regression[J]. Dairy Sci,1997,80:198-204.
[70] Ashwell M.S., Rexroad C.E.Jr, Miller R.H., et al. Mapping economic trait loci forsomatic cell score in Holstein cattle using microsatellite markers and selectivegenotyping[J]. Animal Geneties,1996,27:235-242.
[71]冀德君,陈仁金,杨章平,等中国荷斯坦牛IL8基因SNP-233A/G显著影响体细胞评分[C].中国畜牧兽医学会养牛学分会,2011年学术研讨会论文集
[72]程结南,蔡亚非,王根林,等.脂多糖结合蛋白(LBP)基因中国畜牧兽医学会养牛学分会[C].中国畜牧兽医学会养牛学分会,2011年学术研讨会论文集
[73]曹随忠,李宏滨,姚学萍,等．奶牛乳房炎抗性相关基因Znf313的电子克隆与序列分析[J].中国农学通报,2007,23(1):6-8.
[74] Sugimoto M, Fujikawa A, Womack JE, et al. Evidence that bovine forebrainembryonic zinc finger-like gene influences immune response associated withmastitis resistance[J]. Proc Natl Acad Sci U S A.,2006,103(17):6454-6459.
[75]王兴平,许尚忠,马腾壑,等.牛TLR4基因的遗传多态性与乳房炎的关联分析[J].畜牧兽医学报,2007,38(2):120-124.
[76] McGuire K, Jones M, Werling D, et al. Radiation hybrid mapping of all10characterized bovine Toll-like receptors[J].2006,37(1):47-50.
[77]贾红敏,卢立志,石放雄,等.动物TLR4基因多态性及其抗病相关性研究进展[J].生命科学,2010,22(6):546-550.
[78]白杰,林嘉鹏,袁芳,等．TLR2基因多态性与奶牛体细胞评分的相关性研究[J].畜牧兽医学报,2011,42(3):356-362.
[79]王洪梅,孔振兴,王长法,等．奶牛乳铁蛋白基因５′侧翼区遗传多态性及其与乳腺炎关联性分析[J].遗传,2009,31(4):393-399．
[80]孔振兴.中国荷斯坦奶牛乳铁蛋白基因多态性与乳腺炎相关性的研究[D].吉林农业大学硕士学位论文,2008.5.
[81]陈仁金,杨章平,毛永江,等.中国荷斯坦牛CXCR1基因遗传多态性与体细胞评分的关联分析[J].中国农业科学,2010,43(18):3848-3856．
[82]程维杰,李秋玲,王长法,等．荷斯坦牛HSP70-1基因遗传多态性与乳腺炎抗性关系[J].遗传,2009,31(2):169-174.
[83]张海燕.牛MASPs基因多态性及其与奶牛乳腺炎、产奶性状和补体活性的关联性分析[D].山东师范大学硕士学位论文,2011.
[84] Rupp R, Boichard D. Genetic parameters for clinical mastitis, somatic cell score,production, udder type traits, and milking ease in first lactation Holsteins[J]. JDairy Sci.,1999,82(10):2198-2204.
[85] Jeanne L. Burton, Ronald J. Erskine, DVM. Immunity and mastitis: Some newideas for an old disease[J]. Vet Clin Food Anim,2003,19:1-45.
[86] Fan W, Plaut K, Bramley AJ, et al. Persistency of adenoviral-mediatedlysostaphin expression in goat mammary glands[J]. J Dairy Sci.,2004,87(3):602-608.
[87] Preisler MT, Weber PS, Tempelman RJ, et al. Glucocorticoid receptor down-regulation in neutrophils of periparturient cows[J]. Am J Vet Res.,2000,61(1):14-9.
[88] Schwerin M, Czernek-Sch fer D, Goldammer T, et al. Application of disease-associated differentially expressed genes--mining for functional candidate genesfor mastitis resistance in cattle[J]. Genet Sel Evol.,2003,35(1):19-34.
[89]周雷,王洪梅,王长法,等.中国荷斯坦牛CXCR1基因第二外显子新SNPs与乳腺炎的关联分析[J].畜牧兽医学报,2011,42(8):1063-1070.
[90]鞠志花,李秋玲,黄金明等.中国荷斯坦牛转铁蛋白基因SNPs的检测及其与产奶性能的关系[J].中国农业科学,2011,44(14):3027-3035.
[91] Zhang F X, Kirschning C J, Mancinelli R, et al. Bacterial lipopolysaccharideactivates nuclear factor-κB through Interleukin-1signaling mediators in culturedhuman dermal endothelial cells and mononuclear phagocytes[J]. The Journal ofBiological Chemistry,1999,274(12):7611-7614.
[92] Jensen L E, Muzio M, Mantovani A, et al. IL-1signaling cascade in liver cellsand the involvement of a soluble form of the IL-1receptor accessory protein[J].Journal of Immunology,2000,164:5277-5286.
[93]章卓综述,万敬员,周岐新审校. IRAK家族中TIR信号通路的关键因子[J].免疫学杂志,2006,22(3):76-79.
[94Rosati O, Michael MU. Identification and characterization of murine IRAK-2[J].Biochem Biophys Res Commun,2002,13(297):52-58.
[95] Li X, Qin J. Modulation of toll-interle ukin-1receptor mediated signaling [J]. JMol Med,2005,83(4):258-266.
[96]李亦蕾,郭甫昆,吴曙光.白介素-1受体相关激酶-2反义寡核苷酸对IL-1和TNF诱导PGI2合成的不同影响[J].中国免疫学杂志,2000,16:465-467.
[97] Janssens S, Beyaert R. Functional diversity and regulation of differentinterleukin-1receptor-associated kinase (IRAK) family members[J]. Mol Cell,2003,11:293-302.
[98] Muzio M, Ni J, FengP, et al. IRAK(Pelle) family members IRAK-2and MyD88as proximal mediators of IL-1signaling[J]. Science,1997,278(5343):1612-1615.
[99]文海平. IRAKS在ANTI-β2GPI-β2GPI复合物诱导THP-1细胞表达TF中的作用探讨[D].江苏大学硕士学位论文,2011.
[100] Cao Z, Henzel W J, Gao X. IRAK: A Kinase Associated with the Interleukin-1Receptor[J]. Science,1996,271:1128-1131.
[101] Matthew PH, Luke A, Neill JO. The murine IRAK2encodes four alternativelyspliced isoforms, two of which are inhibitory[J]. J Biol Chem,2004,279(26):27699-27708.
[102] Nishimura M, Naito S. Tissue-specific mRNA expression profiles of humantoll-like receptors and related genes[J]. Biol Pharm Bull,2005,28(5):886-892.
[103]张艳丽,李秀萍,王宁萍,等.毒热平注射液对病毒感染巨噬细胞IRAK4表达的影响[J].时珍国医国药,2010,21(6):1432-1433.
[104]尹卫国,肖建华. IRAK家族在TLR介导的信号通路中的功能和意义[J].中南医学科学杂志,2012,40(2):109-115.
[105] Wesche H, Gao X, Li X, et al. IRAK-M Is a Novel Member of the Pelle/Interleukin-1Receptor-associated Kinase(IRAK)Family[J]. J Biol Chem,1999,274:19403-19410.
[106]韩正强,王楠楠. Toll样受体的研究进展[J].畜牧与兽医,2011,43(12):93-96.
[107]卢震亚. TOLL样受体9在胃癌中的表达及其在发病机制中作用的研究[D].浙江大学博士学位论文.2011年.
[108] Li S, Strelow A, Fontana E J, et al. IRAK-4:A novel member of the IRAKfamily with the properties of an IRAK-kinase[J]. Proc Natl Acad Sci,2002,99:5567-5572.
[109] Suzuki N, Suzuki S, Duncan G S, et al. Severe impairment of interleukin-1andToll-like receptor signalling in mice lacking IRAK-4[J]. Nature,2002,416:750-756.
[110] Marta Muzio. et al. IRAK(Pelle) family mmber IRAK-2and MyD88asproximal mediators of IL-1sigmaling[J]. Science.278(28):1612-1615.
[111]蓝杨. IL-10对脂多糖诱导的Ana-1细胞MyD88/核因子κB通路的抑制作用及其机制探[D].南方医科大学硕士学位论文,2007.
[112]孙冰,韩代书. Toll样受体信号通路的负调控[J].生物化学与生物物理进展2009,36(12):1516-1522.
[113] Huang Y, Li T, Sane Dc, et al. IRAK1serves as a novel regulator essential forlipopolysaccharide-induced interleukin-10gene expression[J]. J Bio Chem,2004,279(49):51697-51703.
[114]孙爱静,陈岳华,钟建平,等. IRAK-M在HSP72保护大鼠肝硬化内毒素血症损伤中的作用研究[P].绍兴市科技局科技登记成果，2010.
[115]王兴平.奶牛TLR4及其信号转导基因的克隆、SNPs检测与乳房炎的关联分析[D].西北农林科技大学博士学位论文.2007.
[116]张宇,孙瑞利综述,胡锦跃审校. Toll样受体4信号转导研究进展[J].国际病理科学与临床杂志,2009,29(1):32-36.
[117] Li S, Strelow A, Fontana E J, et al. IRAK-4: A novel member of the IRAKfamily with the properties of an IRAK-kinase[J]. Proc Natl Acad Sci,2002,99:5567-5572.
[118]金绿英,杨俊.缺血再灌注损伤中Toll样受体4信号转导通路干预机制的研究进展[J].上海医学杂志,2010,32(10):935-938.
[119]李红.溃结灵对溃疡性结肠炎大鼠结肠粘膜TLRs/NF-κB通路的作用[D].广州中医药大学博士学位论文,2007.
[120] Kanakaraj P, Schafer P H, Cavender D E, et al. Interleukin (IL)-1Receptor-associated Kinase (IRAK) requirement for optimal induction of multiple IL-1signaling pathways and IL-6production[J]. J Exp Med,1998,187:2073-2079.
[121] Thomas J A,Allen J L,Tsen M,et al. Impaired Cytokine Signaling in MiceLacking the IL-1Receptor-Associated Kinase[J]. J Immunol,1999,163:978-984.
[122] Kobayashi K, Hernandez L D, Galan J E, et al. IRAK-M is a negative regulatorof Toll-like receptor signaling[J]. Cell,2002,110:191-202.
[123] Picard C, Puel A, Bonnet M, et al. Pyogenic bacterial infections in humans withIRAK-4deficiency[J]. Science,2003,299:2076-2079.
[124] Brad. h. Rovin. et al. Activation of nuclear factor-κB correlates with MCP-1expression by human mesangial cells[J]. Kidney Int,1995,48:1263-1271.
[125]徐宁,于振海,王志强,等. TOLL样受体４及其负性调控因子Tollip在结肠炎大鼠肠黏膜中的表达[J].第二军医大学学报,2012,33(1):32-37.
[126]杨一新,李桂源. LPS所介导的信号转导通路研究进展[J].中南大学学报(医学版),2006,31(1):141-145.
[127] Wang J, Hu Y, Deng W W, et al. Negative Regulation of Toll-like ReceptorsSignaling Pathways[J]. Microbes and infection,2009,11(3):321-327.
[128] Ruckdeschel K, Mannel O, Schr ttner P. Divergence of apoptosis-inducing andpreventing signals in bacteria-faced macrophages through myeloiddifferentiation factor88and IL-1receptor-associated kinase Members[J]. theJournal of Immunology,2002,168:4601-4611.
[129] Huang Y, Li T, Sane D C, et al. IRAK1serves as a novel regulator essential forlipopolysaccharide-induced interleukin-10gene expression[J]. The Journal ofBiological Chemistry,2004,279(49):51697-51703.
[130] Huang Y S, Misior A, Li L W. Novel role and regulation of the Interleukin-1Receptor Associated Kinase (IRAK) family proteins[J]. Molecular Immunology,2005,2(1):36-39.
[131]鲁萍,马飞,王义.基因选择性剪接的生物信息学研究概况[J].遗传,2005,27(6):1001-1006.
[132]倪斌,李麓芸. mRNA选择性剪接与人类疾病[J].国外医学遗传学分册,2005,28(1):10-14.
[133] Johnson JM, Castle J, Garrett-Engele P, et al. Genome-wide survey of humanalternative pre-mRNA splicing with exon junction microarrays[J]. Science,2003,302(5653):2141-2144.
[134]章国卫,宋怀东,陈竺. mRNA选择性剪接的分子机制[J].遗传学报,2004,31(1):102-107.
[135] Hardy M P, O'Neill L A. The murine IRAK2gene encodes four alternativelyspliced isoforms,two of which are inhibitory[J]. the Journal of BiologicalChemistry,2004,279(26):27699-27708.
[136]郭甫坤,李亦蕾,吴曙光,等.反义IRAK2寡核苷酸抑制白介素1生物学效应[J].中国药学杂志,2000,35(1):52-55.
[137]王兴平,罗仍卓么,许尚忠,等.牛白细胞介素1受体相关激酶2（IRAK2）基因的克隆及生物信息学分析[J].农业生物技术学报,2009,17(2):243-248.
[138] Matthew P. Hardy. The Murine Irak2Gene Encodes Four AlternativelySplicedIsoforms, Two of Which Are Inhibitory[J]. Biol Chem.2004,279(26):27699-2708.
[139] O′Neill LAJ, Greene C. Signal transduction pathways activated by the IL1receptor family: ancient signaling machinery in mammals, insects, andplants[J].J Leukoc Biol,1998,63:650-657.
[140]王兴平,罗仍卓么,许尚忠,等.牛IRAK2基因有两种选择性剪接表达产物[J].中国生物化学与分子生物学报,2009,25(3):292-296.
[141] Youzhong Wan, Tae Whan Kim, Michifumi Yamashita, et al. The dual functionsof IRAK2in TLR9–mediated interferon and proinflammatory cytokineproduction[J]. J Immunol,2011,186(5):3006–3014.
[142] Jasper Mullenders, Armida W.M. Fabius, Miranda M., et al. Interleukin-1R–Associated Kinase2Is a Novel Modulator of the Transforming Growth Factor βSignaling Cascade[J]. Mol Cancer Res,2010,8(4):592-603.
[143]高秀丽,景奉香,杨剑波,等.单核苷酸多态性检测分析技术[J].遗传,2005,27(1):110-122.
[144]王威,仇玉兰,孙品,等.几种常规实验室适用的单核营酸多态性检测方法原理与应用[J].职业卫生与应急救援,2006,24(4):177-179.
[145]许晓峰,张晓斌,沙维伟,等.多巴胺受体与5-羟色胺2A受体基因多与迟发性运动障碍的关联[J].中国临床康复,2006,10(34):106-108.
[146]马明义,杜亭,雷娟,等.强直性肌营养不良症的基因诊断[J].山西医药杂志,2012,41(7):646-648.
[147]赵春江,李宁,邓学梅.应用创造酶切位点法检测单碱基突变[J].遗传,2003,25(3):327-329.
[148] Mrode R A,Swanson G J T,Winters M S.Genetic parameters and valuations forsomatic cell count and its relationship with production and type traits in somedairy breeds in the United Kingdoms[J]. Journal of Animal Science,1998,66:569-576.
[149]刘红,高学军,杨名赫,等.奶牛乳腺炎调查及病因分析[J].东北农业大学学报,2009,40(9):82~86.
[150]李晓楠,赵晓彤,丁玉林,等.呼和浩特地区奶牛乳腺炎发病率调查[J].黑龙江畜牧兽医,2013,1：90-91.
[151]薛翠茹,吴文林.奶牛临床型乳房炎的诊治[J].畜牧与饲料科学,2007,3:11.
[152]丁伯良、冯建忠、张国伟.奶牛乳房炎[M].中国农业出版社.2011,158-171.
[153]高玉君.泰安市奶牛乳腺炎的调查与治疗[D].山东农业大学硕士学位论文,2005.
[154]郭小雅,束婧婷,杨章平,等.奶牛隐性乳房炎发生规律的调查分析[J].中国兽医杂志,2005,41(3):23-25.
[155]朱保卫,张晓菊,傅云玲.金华市某奶牛场奶牛隐性乳房炎发病情况分析[J].黄牛杂志,2005,31(2):25-27.
[156]李庆国.奶牛乳房炎发病规律的调研[J].中国畜牧杂志,2006,42（19）：60-61.
[157]何勇军,李炳棠.奶牛乳房炎与主要气象指标的关系[J].河南农业科学,2002,12:40.
[158]胡慧,王亚宾,陈丽颖,等.某规模化奶牛场乳房炎发病规律的调查分析[J].2010,4:892-895.
[159] Miller M P.Tools for population genetic analyses (TFPGA)1.3: A Windowsprogram for the analysis of alloozyme and molecular population genetic data.1997, http://www. marksgeneticsoftware. net/_vti_bin/shtml.exe/tfpga.htm.
[160] Shi Y Y, He L. SHEsis, a powerful software platform for analyses of linkagedisequilibrium, haplotype construction, and genetic association atpolymorphism loci[J]. Cell Research,2005,15(2),97-98.
[161]亓文宝,陈世灿,罗满林,等.牛结核病巢式PCR快速检测方法的建立[J].中国兽医科学,2006,36(10):815-819.
[162] Kwok S, Kellogg D E, McKinney N, et al. Effects of primer-templatemismatches on the polymerase chain reaction: human immunodeficiency virustype1model studies[J]. Nucleic Acids Research,1990,18(4):999-1005.
[163]马明义,张思仲.联合应用巢式PCR和创造酶切位点法检测单核苷酸改变[J].中国优生与遗传杂志,2007,15(6):13-14.
[164] Fallin D, Cohen A, Essioux L, Chumakov I, et al. Genetic analysis ofcase/control data using Estimated Haplotype Frequencies: Application to APOElocus variationand Alzheimer’s disease. Genome Research,2001,11(1):143-151.
[165]常虹.基因诊断方法的研究与进展[J].中国组织工程研究与临床康复,2008,12(37):7355-7358.
[166]王瑞,杨水云. PCR-SSCP快速检测结核分枝杆菌耐利福平rpoB基因的研究[J].现代检验医学杂志,2008,23(5):18-20.
[167]何秀云,庄玉辉,李国利,等. PCR-SSCP方法用于痰标本中结核分支杆菌rPOB基因突变检测[J].中国防痨杂志,1997,19(3),126-128.
[168]周铭涛,高洪,肖鹏,等. PCR-SSCP技术应用研究进展[J].动物医学进展,2009,30(6):90-93.
[2]尹荣兰,王浩然,张艳晶,等.奶牛乳腺炎金黄色葡萄球菌CIFA核酸疫苗的构建及免疫原性试验[J].中国兽医学报,2012,32(4):439-542.
[3]王桂琴.奶牛乳腺炎的病因及防治[J].上海畜牧兽医通讯,2005,5:56-57.
[4] Harmon R J. Symposium: Mastitis and genetic evaluation for somatic cell count:Physiology of mastitis and factors affecting somatic cell counts[J]. Dairy Sci,1994,77(7):2103-2112.
[5]王会珍.奶牛乳房炎的危害及分类[J].山东省农业管理干部学院学报,2007,23(4):151-152.
[6]蒋春茂,周新民,周广生,等．奶牛乳房炎研究进展[J].中国畜牧兽医,2004(5):36-38．
[7]严作廷,王东升,王旭荣,等.我国奶牛主要疾病研究进展[J].中国草食动物2011,31(6):69-72.
[8]刘新勃,田国宁.潍坊地区奶牛隐性乳腺炎感染率调查及防治效果考核[J].中国动物检疫,2006,23(1):41-42.
[9]胡建春.不同饲养环境下奶牛隐性乳腺炎流行病学调查[J].当代畜牧,2005,34(2):19-21.
[10]易本驰.奶牛隐性乳腺炎调查及病原分离鉴定[J].上海畜牧兽医通讯,2007,1:221.
[11]赵香汝,李寸欣,郑雪花,等.张家口地区奶牛隐性乳腺炎的流行特点[J].中国动物检疫,2010,27(1):52-53.
[12]吕润全,刘文杰,郭伟.南京地区奶牛隐性乳腺炎的调查与分析[J].江苏农业科学,2010,2:234-235.
[13]李宏胜,郁杰.奶牛乳房炎病原菌人工诱发奶山羊急性乳房炎试验[J].动物医学进展,2004,25(4):84-87.
[14]许毅.奶牛乳房炎发病原因综述[J].饲料广角,2003,21:38-40.
[15]刘锡武,马保臣.奶牛乳腺炎的调查报告[J].兽药与饲料添加剂,2004,9(2):27-28．
[16]王成,童洁,高东.奶牛隐性乳房炎的检测与治疗效果观察[J].畜牧与兽医1998,30(3):123-124.
[17]王海军,王赞江.奶牛乳房炎的病因及综合防治[J].2006,32(5):101-104.
[18]李宗方,董喜林,叶东东等.荷斯坦牛与新疆褐牛牛奶体细胞数对比分析[J].新疆农业科学,2009,46(6):1336-1340.
[19]王希春,李培,吴金节.奶牛隐性乳房炎对牛奶中体细胞数及品质的影响[J].中国奶牛,2008,4:49-51.
[20]赵兴,徐新明,邓江玲,等.奶牛乳中体细胞数与产奶性状的相关分析[J].草食家畜,2011,152(3):21-23.
[21]周亚平,刘琴,施开平,等.乳体细胞数与产奶量、乳成分的关系研究[J].中国奶牛,2011,4:40-42.
[22]周木清,金尔光,周世同,等. DHI报告在奶牛饲养管理中的分析与应用[J].现代农业科技,2006,9:65-68.
[23] KOLDWIJE，EMANUWLSONU. Relation of milk Production loss to milksomatic cell count[J]. ACAT vet Scand,1999,40:47-56.
[24]屈常林,王怀娜,蓝响.牛奶体细胞数及牛乳中酶活性与隐性乳腺炎致病菌之间的相关性[J].中国奶牛,2010,3:39-41.
[25] H.Dosogne, F.Vangroenweghe, J.Mehrzad. et al. Differential leukocyte countmethod for bovine low somatic cell count milk[J]. Journal of Dairy Science2003,86(3):828-834.
[26]王芳,胡松华.体细胞含量与牛奶质量的关系[J].中国奶牛,2005,(4):51-52.
[27]张慧林,余文文,刘小林,等.牛乳中体细胞数与产奶量和乳成分的相关分析[J].西北农业学报,2010,1(4):1-4.
[28]郝建国.日本学者对体细胞数与乳房炎关系的论述[J].中国奶牛,2002,1:52-54.
[29]陈华林.体细胞数在奶牛乳房卫生保健工作中的应用[J].中国奶牛,2000,6:49-51.
[30]麻士卫,陈永福,王记成,等.牛乳体细胞数与乳蛋白含量相关性的研究[J].中国乳品工业,2006,34(6):27-31.
[31] Shamay A，Shapiro F，Mabjeesh SJ，et al. Casein-derived phosphopeptidesdisrupt tight junction integrity, and precipitously dry up milk secretion in goats[J]. Life sciences,2002,70(23):2707-2719.
[32]刘文娇,孙少华.线性模型对影响奶牛产奶性能的主要相关因素分析[J].中国奶牛,2010,6:24-26.
[33]程广龙,江喜春,赵辉玲,等.牛奶中高体细胞数的危害及调控措施畜牧与饲料科学[J].2009,30(4):65-66.
[34] Ma Y, Ryan C. Effects of somatic cell count on quality and shelf-life ofpasteurized fluid milk[J]. J Dairy Sci,2000,83:264-274.
[35]储明星,石万海,邝霞,等.浅谈奶牛乳房炎[J].中国奶牛,2001(3):39-40.
[36]邢慧敏,云振宇,李妍,等.牛乳体细胞数与乳中离子含量相关性的研究[J].食品科学2007,28(5)53:53-56.
[37]叶纪梅,王加启,赵国琦.细胞数过高对乳制品品质的影响[J].中国奶牛,2006,5:41-44.
[38] Da Y, Grossman M, Misztal I, et al. Estimation of genetic parameters for somaticcell score in Holsteins[J]. Journal of Dairy Science,1992,75(8):2265-2271.
[39] Mark T, Fikse W F, Emanuelson U, et al. International genetic evaluations ofHolstein sires for milk somatic cell and clinical mastitis[J]. Journal of DairyScience,2002,85(9):2384-2392.
[40] Schutz M M. Genetic evaluation of somatic cell scores for United States dairycattle[J]. Journal of Dairy Science,1994,77(7):2113-2129.
[41] SHOOK G E. Approaches to summarizing somatic cell counts which improveinterpretability[M]. Proc. Natl. Mastitis Countil, Arlington,1982, VA:150-166.
[42]李建斌,孙少华,田雨泽.中国荷斯坦牛乳中体细胞数变化规律的研究[J].新疆农业科学,2009,46(6):1336-1340.
[43]郑怀军,张永根,杨贵,等.对通过DHI改进奶牛场生产管理的观察与分析[J].中国奶牛,2006(5):24-27.
[44]毛永江,杨章平.南方地区中国荷斯坦牛乳中体细胞数变化规律的研究[J].中国奶牛,2007年会论文集·159-161.
[45]李世平,毛永江,常洪,等.南方地区中国荷斯坦牛乳中体细胞数变化规律的研究[J].中国畜牧杂志,2008,44(3):7-9.
[46]赵连生,王加启,郑楠,等.牛奶质量安全主要风险因子分析Ⅶ.体细胞数和菌落总数[J].中国畜牧兽医,2012,39(7):1-5.
[47]刘岩,王艳鸽,张鑫.食品中抗生素检测技术研究进展[J].山西食品工业,2005,3:38-41,43.
[48] Heringstad B, Klemetsdal q Ruane G. Responses to selection against clinicalmastitis in the Norwegian cattle population[J]. Anim Sci,2001,51:155-165.
[49] Rachel Didier Boichard. Genetics of resisitance to mastitis in dairy cattle[J]. Vet.Res.,2003,34:671-688.
[50] Heringstad, B., Klemetsdal, G., Ruane, J. Clinical mastitis in Norwegian cattle:frequency, variance components, and genetic correlation with protein yield[J].Dairy Sci,1999,82:1325-1330.
[51] T. Mark,W.F. Fikse, U. Emanuelson, et al. International Genetic Evaluations ofHolstein Sires for Milk Somatic Cell and Clinical Mastitis[J]. Journal of DairyScience,2002,85(9):2384-2392.
[52] R.A Mrode, G.J.T Swanson. Estimation of genetic parameters for somatic cellcount in the first three lactations using random regression[J]. LivestockProduction Science,2003,79(2–3):239-247.
[53]高树新. BoLA基因多态性及其与奶牛乳腺炎的关联研究[D].内蒙古农业大学博士学位论文,2005.
[54]张才骏.遗传因素在牛产科疾病中的作用[J].国外兽医学-畜禽疾病,1991,2:1-5.
[55] J Harmon, R.J., Physiology of mastitis and factors affecting somatic cellcounts[J]. Dairy Sci,1994,77:2103-2112.
[56] J.I. Weller, A. Saran, Y. Zeliger. Genetic and environmental relationships amongsomatic cell count, bacterial infection, and clinical mastitis[J]. Journal of DairyScience,1992,75(9:2532-2540.
[57] Johann C., Detilleux, et al. David H. Kelley. Mastitis of periparturient Holsteincattle: a phenotypic and genetic study[J]. Journal of Dairy Science1995,78(10):2285-2293.
[58] Nash DL, Rogers GW, Cooper JB, et al. Heritability of clinical mastitis incidenceand relationships with sire transmitting abilities for somatic cell score, udder typetraits, productive life, and protein yield[J]. J Dairy Sci.2000,83(10):2350-2360.
[59] J. P s, E.A. M ntysaari. Relationships Between Clinical Mastitis, Somatic CellScore, and Production for the First Three Lactations of Finnish Ayrshire[J].Journal of Dairy Science1996,79(7):1284-1291.
[60] T Mark, WF Fikse, U Emanuelson, et al. International genetic evaluations ofHolstein sires for milk somatic cell and clinical mastitis[J]. Journal of dairyscience, Journal of Dairy Science,2002,85(9):2384-2392.
[61] Shook GE, Schutz MM. Selection on somatic cell score to improve resistance tomastitis in the United States[J]. J Dairy Sci.1994,77(2):648-58.
[62] Banos G, Shook G E. Genotype by environment interaction and geneticcorrelations among parities for somatic cell count and milk yield[J]. Journal ofDairy Science,1990,73(9):2563-2573.
[63] Lund T, Miglior F, Dekkers J C M, et al. Genetic relationships between clinicalmastitis, somatic cell count, and udder conformation in Danish Holsteins[J].Livestock Production Science,1994,39(3):243-251.
[64] Fallin D, Cohen A, Essioux L, et al. Genetic analysis of case/control data usingEstimated Haplotype Frequencies: Application to APOE locus variation andAlzheimer’s disease[J]. Genome Research,2001,11(1):143-151.
[65]肖正中,赖松家.奶牛分子育种的研究进展[J].畜牧与兽医,2003,35(6):41-44.
[66]魏伟,苗永旺.奶牛乳腺炎抗性候选基因多态性研究进展[J].中国牛业科学2011,37(6):49-51,56.
[67] Wojdak-Maksymiec K, Kmie M, Zukiewicz A. Associations between defensinpolymorphism and somatic cell count in milk and milk utility traits in Jerseydairy cows. Journal of Veterinary Medicine Series A-Physiology Pathology[J].Clinical Medicine,2006,53(10):495-500.
[68] Schwerin M, Kühn C, Brunner R, et al. QTL mapping and mining functionalcandidate genes affecting health-the German ADR QTL Dairy Cattle Project[J].Animal Science Papers and Reports,2004,22(1),95-100.
[69] Vilkki H.J., Dekoning D.I., BinK, et al. Multiple marker mapping of quantitativetrait loci of Finnish diary cattle by regression[J]. Dairy Sci,1997,80:198-204.
[70] Ashwell M.S., Rexroad C.E.Jr, Miller R.H., et al. Mapping economic trait loci forsomatic cell score in Holstein cattle using microsatellite markers and selectivegenotyping[J]. Animal Geneties,1996,27:235-242.
[71]冀德君,陈仁金,杨章平,等中国荷斯坦牛IL8基因SNP-233A/G显著影响体细胞评分[C].中国畜牧兽医学会养牛学分会,2011年学术研讨会论文集
[72]程结南,蔡亚非,王根林,等.脂多糖结合蛋白(LBP)基因中国畜牧兽医学会养牛学分会[C].中国畜牧兽医学会养牛学分会,2011年学术研讨会论文集
[73]曹随忠,李宏滨,姚学萍,等．奶牛乳房炎抗性相关基因Znf313的电子克隆与序列分析[J].中国农学通报,2007,23(1):6-8.
[74] Sugimoto M, Fujikawa A, Womack JE, et al. Evidence that bovine forebrainembryonic zinc finger-like gene influences immune response associated withmastitis resistance[J]. Proc Natl Acad Sci U S A.,2006,103(17):6454-6459.
[75]王兴平,许尚忠,马腾壑,等.牛TLR4基因的遗传多态性与乳房炎的关联分析[J].畜牧兽医学报,2007,38(2):120-124.
[76] McGuire K, Jones M, Werling D, et al. Radiation hybrid mapping of all10characterized bovine Toll-like receptors[J].2006,37(1):47-50.
[77]贾红敏,卢立志,石放雄,等.动物TLR4基因多态性及其抗病相关性研究进展[J].生命科学,2010,22(6):546-550.
[78]白杰,林嘉鹏,袁芳,等．TLR2基因多态性与奶牛体细胞评分的相关性研究[J].畜牧兽医学报,2011,42(3):356-362.
[79]王洪梅,孔振兴,王长法,等．奶牛乳铁蛋白基因５′侧翼区遗传多态性及其与乳腺炎关联性分析[J].遗传,2009,31(4):393-399．
[80]孔振兴.中国荷斯坦奶牛乳铁蛋白基因多态性与乳腺炎相关性的研究[D].吉林农业大学硕士学位论文,2008.5.
[81]陈仁金,杨章平,毛永江,等.中国荷斯坦牛CXCR1基因遗传多态性与体细胞评分的关联分析[J].中国农业科学,2010,43(18):3848-3856．
[82]程维杰,李秋玲,王长法,等．荷斯坦牛HSP70-1基因遗传多态性与乳腺炎抗性关系[J].遗传,2009,31(2):169-174.
[83]张海燕.牛MASPs基因多态性及其与奶牛乳腺炎、产奶性状和补体活性的关联性分析[D].山东师范大学硕士学位论文,2011.
[84] Rupp R, Boichard D. Genetic parameters for clinical mastitis, somatic cell score,production, udder type traits, and milking ease in first lactation Holsteins[J]. JDairy Sci.,1999,82(10):2198-2204.
[85] Jeanne L. Burton, Ronald J. Erskine, DVM. Immunity and mastitis: Some newideas for an old disease[J]. Vet Clin Food Anim,2003,19:1-45.
[86] Fan W, Plaut K, Bramley AJ, et al. Persistency of adenoviral-mediatedlysostaphin expression in goat mammary glands[J]. J Dairy Sci.,2004,87(3):602-608.
[87] Preisler MT, Weber PS, Tempelman RJ, et al. Glucocorticoid receptor down-regulation in neutrophils of periparturient cows[J]. Am J Vet Res.,2000,61(1):14-9.
[88] Schwerin M, Czernek-Sch fer D, Goldammer T, et al. Application of disease-associated differentially expressed genes--mining for functional candidate genesfor mastitis resistance in cattle[J]. Genet Sel Evol.,2003,35(1):19-34.
[89]周雷,王洪梅,王长法,等.中国荷斯坦牛CXCR1基因第二外显子新SNPs与乳腺炎的关联分析[J].畜牧兽医学报,2011,42(8):1063-1070.
[90]鞠志花,李秋玲,黄金明等.中国荷斯坦牛转铁蛋白基因SNPs的检测及其与产奶性能的关系[J].中国农业科学,2011,44(14):3027-3035.
[91] Zhang F X, Kirschning C J, Mancinelli R, et al. Bacterial lipopolysaccharideactivates nuclear factor-κB through Interleukin-1signaling mediators in culturedhuman dermal endothelial cells and mononuclear phagocytes[J]. The Journal ofBiological Chemistry,1999,274(12):7611-7614.
[92] Jensen L E, Muzio M, Mantovani A, et al. IL-1signaling cascade in liver cellsand the involvement of a soluble form of the IL-1receptor accessory protein[J].Journal of Immunology,2000,164:5277-5286.
[93]章卓综述,万敬员,周岐新审校. IRAK家族中TIR信号通路的关键因子[J].免疫学杂志,2006,22(3):76-79.
[94Rosati O, Michael MU. Identification and characterization of murine IRAK-2[J].Biochem Biophys Res Commun,2002,13(297):52-58.
[95] Li X, Qin J. Modulation of toll-interle ukin-1receptor mediated signaling [J]. JMol Med,2005,83(4):258-266.
[96]李亦蕾,郭甫昆,吴曙光.白介素-1受体相关激酶-2反义寡核苷酸对IL-1和TNF诱导PGI2合成的不同影响[J].中国免疫学杂志,2000,16:465-467.
[97] Janssens S, Beyaert R. Functional diversity and regulation of differentinterleukin-1receptor-associated kinase (IRAK) family members[J]. Mol Cell,2003,11:293-302.
[98] Muzio M, Ni J, FengP, et al. IRAK(Pelle) family members IRAK-2and MyD88as proximal mediators of IL-1signaling[J]. Science,1997,278(5343):1612-1615.
[99]文海平. IRAKS在ANTI-β2GPI-β2GPI复合物诱导THP-1细胞表达TF中的作用探讨[D].江苏大学硕士学位论文,2011.
[100] Cao Z, Henzel W J, Gao X. IRAK: A Kinase Associated with the Interleukin-1Receptor[J]. Science,1996,271:1128-1131.
[101] Matthew PH, Luke A, Neill JO. The murine IRAK2encodes four alternativelyspliced isoforms, two of which are inhibitory[J]. J Biol Chem,2004,279(26):27699-27708.
[102] Nishimura M, Naito S. Tissue-specific mRNA expression profiles of humantoll-like receptors and related genes[J]. Biol Pharm Bull,2005,28(5):886-892.
[103]张艳丽,李秀萍,王宁萍,等.毒热平注射液对病毒感染巨噬细胞IRAK4表达的影响[J].时珍国医国药,2010,21(6):1432-1433.
[104]尹卫国,肖建华. IRAK家族在TLR介导的信号通路中的功能和意义[J].中南医学科学杂志,2012,40(2):109-115.
[105] Wesche H, Gao X, Li X, et al. IRAK-M Is a Novel Member of the Pelle/Interleukin-1Receptor-associated Kinase(IRAK)Family[J]. J Biol Chem,1999,274:19403-19410.
[106]韩正强,王楠楠. Toll样受体的研究进展[J].畜牧与兽医,2011,43(12):93-96.
[107]卢震亚. TOLL样受体9在胃癌中的表达及其在发病机制中作用的研究[D].浙江大学博士学位论文.2011年.
[108] Li S, Strelow A, Fontana E J, et al. IRAK-4:A novel member of the IRAKfamily with the properties of an IRAK-kinase[J]. Proc Natl Acad Sci,2002,99:5567-5572.
[109] Suzuki N, Suzuki S, Duncan G S, et al. Severe impairment of interleukin-1andToll-like receptor signalling in mice lacking IRAK-4[J]. Nature,2002,416:750-756.
[110] Marta Muzio. et al. IRAK(Pelle) family mmber IRAK-2and MyD88asproximal mediators of IL-1sigmaling[J]. Science.278(28):1612-1615.
[111]蓝杨. IL-10对脂多糖诱导的Ana-1细胞MyD88/核因子κB通路的抑制作用及其机制探[D].南方医科大学硕士学位论文,2007.
[112]孙冰,韩代书. Toll样受体信号通路的负调控[J].生物化学与生物物理进展2009,36(12):1516-1522.
[113] Huang Y, Li T, Sane Dc, et al. IRAK1serves as a novel regulator essential forlipopolysaccharide-induced interleukin-10gene expression[J]. J Bio Chem,2004,279(49):51697-51703.
[114]孙爱静,陈岳华,钟建平,等. IRAK-M在HSP72保护大鼠肝硬化内毒素血症损伤中的作用研究[P].绍兴市科技局科技登记成果，2010.
[115]王兴平.奶牛TLR4及其信号转导基因的克隆、SNPs检测与乳房炎的关联分析[D].西北农林科技大学博士学位论文.2007.
[116]张宇,孙瑞利综述,胡锦跃审校. Toll样受体4信号转导研究进展[J].国际病理科学与临床杂志,2009,29(1):32-36.
[117] Li S, Strelow A, Fontana E J, et al. IRAK-4: A novel member of the IRAKfamily with the properties of an IRAK-kinase[J]. Proc Natl Acad Sci,2002,99:5567-5572.
[118]金绿英,杨俊.缺血再灌注损伤中Toll样受体4信号转导通路干预机制的研究进展[J].上海医学杂志,2010,32(10):935-938.
[119]李红.溃结灵对溃疡性结肠炎大鼠结肠粘膜TLRs/NF-κB通路的作用[D].广州中医药大学博士学位论文,2007.
[120] Kanakaraj P, Schafer P H, Cavender D E, et al. Interleukin (IL)-1Receptor-associated Kinase (IRAK) requirement for optimal induction of multiple IL-1signaling pathways and IL-6production[J]. J Exp Med,1998,187:2073-2079.
[121] Thomas J A,Allen J L,Tsen M,et al. Impaired Cytokine Signaling in MiceLacking the IL-1Receptor-Associated Kinase[J]. J Immunol,1999,163:978-984.
[122] Kobayashi K, Hernandez L D, Galan J E, et al. IRAK-M is a negative regulatorof Toll-like receptor signaling[J]. Cell,2002,110:191-202.
[123] Picard C, Puel A, Bonnet M, et al. Pyogenic bacterial infections in humans withIRAK-4deficiency[J]. Science,2003,299:2076-2079.
[124] Brad. h. Rovin. et al. Activation of nuclear factor-κB correlates with MCP-1expression by human mesangial cells[J]. Kidney Int,1995,48:1263-1271.
[125]徐宁,于振海,王志强,等. TOLL样受体４及其负性调控因子Tollip在结肠炎大鼠肠黏膜中的表达[J].第二军医大学学报,2012,33(1):32-37.
[126]杨一新,李桂源. LPS所介导的信号转导通路研究进展[J].中南大学学报(医学版),2006,31(1):141-145.
[127] Wang J, Hu Y, Deng W W, et al. Negative Regulation of Toll-like ReceptorsSignaling Pathways[J]. Microbes and infection,2009,11(3):321-327.
[128] Ruckdeschel K, Mannel O, Schr ttner P. Divergence of apoptosis-inducing andpreventing signals in bacteria-faced macrophages through myeloiddifferentiation factor88and IL-1receptor-associated kinase Members[J]. theJournal of Immunology,2002,168:4601-4611.
[129] Huang Y, Li T, Sane D C, et al. IRAK1serves as a novel regulator essential forlipopolysaccharide-induced interleukin-10gene expression[J]. The Journal ofBiological Chemistry,2004,279(49):51697-51703.
[130] Huang Y S, Misior A, Li L W. Novel role and regulation of the Interleukin-1Receptor Associated Kinase (IRAK) family proteins[J]. Molecular Immunology,2005,2(1):36-39.
[131]鲁萍,马飞,王义.基因选择性剪接的生物信息学研究概况[J].遗传,2005,27(6):1001-1006.
[132]倪斌,李麓芸. mRNA选择性剪接与人类疾病[J].国外医学遗传学分册,2005,28(1):10-14.
[133] Johnson JM, Castle J, Garrett-Engele P, et al. Genome-wide survey of humanalternative pre-mRNA splicing with exon junction microarrays[J]. Science,2003,302(5653):2141-2144.
[134]章国卫,宋怀东,陈竺. mRNA选择性剪接的分子机制[J].遗传学报,2004,31(1):102-107.
[135] Hardy M P, O'Neill L A. The murine IRAK2gene encodes four alternativelyspliced isoforms,two of which are inhibitory[J]. the Journal of BiologicalChemistry,2004,279(26):27699-27708.
[136]郭甫坤,李亦蕾,吴曙光,等.反义IRAK2寡核苷酸抑制白介素1生物学效应[J].中国药学杂志,2000,35(1):52-55.
[137]王兴平,罗仍卓么,许尚忠,等.牛白细胞介素1受体相关激酶2（IRAK2）基因的克隆及生物信息学分析[J].农业生物技术学报,2009,17(2):243-248.
[138] Matthew P. Hardy. The Murine Irak2Gene Encodes Four AlternativelySplicedIsoforms, Two of Which Are Inhibitory[J]. Biol Chem.2004,279(26):27699-2708.
[139] O′Neill LAJ, Greene C. Signal transduction pathways activated by the IL1receptor family: ancient signaling machinery in mammals, insects, andplants[J].J Leukoc Biol,1998,63:650-657.
[140]王兴平,罗仍卓么,许尚忠,等.牛IRAK2基因有两种选择性剪接表达产物[J].中国生物化学与分子生物学报,2009,25(3):292-296.
[141] Youzhong Wan, Tae Whan Kim, Michifumi Yamashita, et al. The dual functionsof IRAK2in TLR9–mediated interferon and proinflammatory cytokineproduction[J]. J Immunol,2011,186(5):3006–3014.
[142] Jasper Mullenders, Armida W.M. Fabius, Miranda M., et al. Interleukin-1R–Associated Kinase2Is a Novel Modulator of the Transforming Growth Factor βSignaling Cascade[J]. Mol Cancer Res,2010,8(4):592-603.
[143]高秀丽,景奉香,杨剑波,等.单核苷酸多态性检测分析技术[J].遗传,2005,27(1):110-122.
[144]王威,仇玉兰,孙品,等.几种常规实验室适用的单核营酸多态性检测方法原理与应用[J].职业卫生与应急救援,2006,24(4):177-179.
[145]许晓峰,张晓斌,沙维伟,等.多巴胺受体与5-羟色胺2A受体基因多与迟发性运动障碍的关联[J].中国临床康复,2006,10(34):106-108.
[146]马明义,杜亭,雷娟,等.强直性肌营养不良症的基因诊断[J].山西医药杂志,2012,41(7):646-648.
[147]赵春江,李宁,邓学梅.应用创造酶切位点法检测单碱基突变[J].遗传,2003,25(3):327-329.
[148] Mrode R A,Swanson G J T,Winters M S.Genetic parameters and valuations forsomatic cell count and its relationship with production and type traits in somedairy breeds in the United Kingdoms[J]. Journal of Animal Science,1998,66:569-576.
[149]刘红,高学军,杨名赫,等.奶牛乳腺炎调查及病因分析[J].东北农业大学学报,2009,40(9):82~86.
[150]李晓楠,赵晓彤,丁玉林,等.呼和浩特地区奶牛乳腺炎发病率调查[J].黑龙江畜牧兽医,2013,1：90-91.
[151]薛翠茹,吴文林.奶牛临床型乳房炎的诊治[J].畜牧与饲料科学,2007,3:11.
[152]丁伯良、冯建忠、张国伟.奶牛乳房炎[M].中国农业出版社.2011,158-171.
[153]高玉君.泰安市奶牛乳腺炎的调查与治疗[D].山东农业大学硕士学位论文,2005.
[154]郭小雅,束婧婷,杨章平,等.奶牛隐性乳房炎发生规律的调查分析[J].中国兽医杂志,2005,41(3):23-25.
[155]朱保卫,张晓菊,傅云玲.金华市某奶牛场奶牛隐性乳房炎发病情况分析[J].黄牛杂志,2005,31(2):25-27.
[156]李庆国.奶牛乳房炎发病规律的调研[J].中国畜牧杂志,2006,42（19）：60-61.
[157]何勇军,李炳棠.奶牛乳房炎与主要气象指标的关系[J].河南农业科学,2002,12:40.
[158]胡慧,王亚宾,陈丽颖,等.某规模化奶牛场乳房炎发病规律的调查分析[J].2010,4:892-895.
[159] Miller M P.Tools for population genetic analyses (TFPGA)1.3: A Windowsprogram for the analysis of alloozyme and molecular population genetic data.1997, http://www. marksgeneticsoftware. net/_vti_bin/shtml.exe/tfpga.htm.
[160] Shi Y Y, He L. SHEsis, a powerful software platform for analyses of linkagedisequilibrium, haplotype construction, and genetic association atpolymorphism loci[J]. Cell Research,2005,15(2),97-98.
[161]亓文宝,陈世灿,罗满林,等.牛结核病巢式PCR快速检测方法的建立[J].中国兽医科学,2006,36(10):815-819.
[162] Kwok S, Kellogg D E, McKinney N, et al. Effects of primer-templatemismatches on the polymerase chain reaction: human immunodeficiency virustype1model studies[J]. Nucleic Acids Research,1990,18(4):999-1005.
[163]马明义,张思仲.联合应用巢式PCR和创造酶切位点法检测单核苷酸改变[J].中国优生与遗传杂志,2007,15(6):13-14.
[164] Fallin D, Cohen A, Essioux L, Chumakov I, et al. Genetic analysis ofcase/control data using Estimated Haplotype Frequencies: Application to APOElocus variationand Alzheimer’s disease. Genome Research,2001,11(1):143-151.
[165]常虹.基因诊断方法的研究与进展[J].中国组织工程研究与临床康复,2008,12(37):7355-7358.
[166]王瑞,杨水云. PCR-SSCP快速检测结核分枝杆菌耐利福平rpoB基因的研究[J].现代检验医学杂志,2008,23(5):18-20.
[167]何秀云,庄玉辉,李国利,等. PCR-SSCP方法用于痰标本中结核分支杆菌rPOB基因突变检测[J].中国防痨杂志,1997,19(3),126-128.
[168]周铭涛,高洪,肖鹏,等. PCR-SSCP技术应用研究进展[J].动物医学进展,2009,30(6):90-93.