牛主要抗病候选基因的研究进展

doi:10.16431/j.cnki.1671-7236.2018.07.023

摘要/Abstract

摘要：

牛抗病基因与其自身的抗病性和免疫能力有一定的相关性，因此研究相关抗病基因对提高牛自身免疫能力和选育优良后代有重要意义，文章着重介绍了国内外关于天然抗性相关巨噬细胞蛋白1（natual resistant macrophage protein 1，Nramp1）、主要组织相容性复合物（major histocompatibility complex，MHC）、甘露糖结合凝集素（maflnan binding lectin，MBL）、Toll样受体（Toll-like receptors，TLR）及干扰素基因（interferon，IFN）与牛某些疾病相关性的研究进展，及其是否可用于后代育种的分子标记，如MHC与奶牛的乳房炎密切相关；牛TLR4基因的外显子1760 C>T突变中的CC基因型可作为奶牛乳房炎抗性筛选中的分子标记等。笔者认为研究这些抗病基因可更深层次了解牛的抗病机制，同时借助先进的技术手段如分子标记、基因工程等，可更好的选育出抗病后代，抗病基因在育种中的应用将是未来研究抗病性和免疫能力的主要方向。

关键词: 牛; 抗病候选基因; 研究进展

Abstract:

In this paper,the research progress of immune-related partial resistance genes (MHC,Nramp1,MBL,TLR and IFN) in cattle at home and abroad are briefly reviewed.Because of the relationship between the disease resistance genes of cattle and their own disease resistance and immunity,it is very meaningful to study the related resistance genes to improve the autoimmunity of cattle and to breed the fine offspring.This article focuses on the domestic and foreign study progress on the candidate resistance genes (Nramp 1,MHC,MBL,TLR and IFN) to certain diseases in cattle and whether it can be used for future generations of breeding molecular markers,such as MHC is closely related to dairy cow's mastitis;The CC genotype in the 1760 C>T mutation of TLR4 gene in cattle can be used as a molecular marker in the screening of resistance to mastitis in dairy cows.We believe that the study of these disease-resistance genes can give us a deeper understanding of the disease-resistant mechanism.At the same time, advanced techniques such as molecular markers and genetic engineering can be used to breed disease-resistant offspring,and the application of anti-disease genes in breeding will be the main direction of studying disease resistance and immunity in the future.

Key words: cattle; disease-resistant candidate genes; research progress

中图分类号:

S813.2

孙宏宇, 索朗斯珠, 徐业芬, 牛家强, 姚一龙, 张入丹, 王冬经. 牛主要抗病候选基因的研究进展[J]. 《中国畜牧兽医》, 2018, 45(7): 1912-1918.

SUN Hongyu, SUOLANG Sizhu, XU Yefen, NIU Jiaqiang, YAO Yilong, ZHANG Rudan, WANG Dongjing. Research Progress of Major Disease Resistance Candidate Genes in Cattle[J]. , 2018, 45(7): 1912-1918.

参考文献

[1] 袁峥嵘.动物抗病育种研究进展[J].畜牧与兽医,2007,39(9):68-70. YUAN Z R.Research advances on animal disease resistance breeding[J].Animal Husbandry & Veterinary Medicine,2007,39(9):68-70.(in Chinese)
[2] 王雷,王宝维,杨志刚.抗病育种在家禽育种中的应用[J].中国家禽,2005,27(22):53-54. WANG L,WANG B W,YANG Z G.Application of disease resistance breeding in poultry breeding[J].China Poultry,2005,27(22):53-54.(in Chinese)
[3] 孙东晓,张沅.反刍家畜主组织相容性复合物的研究进展[J].中国畜牧杂志,2002,38(5):46-47. SUN D X,ZHANG Y.Progress of MHC in rumi-nant[J].Chinese Journal of Animal Science,2002,38(5):46-47.(in Chinese)
[4] AMORENA B,STONE W H.Serologically defined (SD) locus in cattle[J].Science,1978,201(4351):159-160.
[5] FRIES R,HEDIGER R,STRANZINGER G.Tentative chromosomal localization of the bovine major histocompatibility complex by in situ hybridization[J].Animal Genetics,1986,17(4):287-294.
[6] 王学清,李魁英,裴翠娟,等.中国荷斯坦牛BoLA-DRB3基因的mRNA表达研究[J].华北农学报,2013,28(4):19-22. WANG X Q,LI K Y,PEI C J,et al.Expression of BoLA-DRB3 mRNA in Chinese Holstein cows[J].Acta Agriculturae Boreali-Sinica,2013,28(4):19-22.(in Chinese)
[7] 蒲兰屏,席冬梅,樊月园,等.犏牛主要组织相容性复合物DRA基因(MHC-class Ⅱ-DRA)的分子特征分析[J].中国畜牧兽医,2012,39(9):12-17. PU L P,XI D M,FAN Y Y,et al.Analysis of the molecular characteristics of Chinese yakow major histocompatibility complex DRA gene (MHC-classⅡ-DRA)[J].China Animal Husbandry & Veterinary Medicine, 2012,39(9):12-17.(in Chinese)
[8] 孙菲菲,刘桂芬,万发春,等.渤海黑牛BOLA-DQA2基因SNPs多态性与生长性状的关联性分析[J].西南农业学报,2012,25(1):271-275. SUN F F,LIU G F,WAN F C,et al.Association of PCR-SSCP polymorphisms of BOLA-DQA2 gene with growth traits of Chinese Bohai Black cattle[J].Southwest China Journal of Agricultural Sciences, 2012, 25(1):271-275.(in Chinese)
[9] GOWANE G R,SHARMA A K,SANKAR M, et al.Association of BoLA DRB3 alleles with variability in immune response among the crossbred cattle vaccinated for foot-and-mouth disease (FMD)[J].Research in Veterinary Science,2013,95(1):156-163.
[10] 王勃,贺晓丽,王勇胜,等.BoLA-Ⅰ类基因在牛体细胞克隆胚早期发育中的表达[J].中国兽医学报,2015, 35(1):103-108. WANG B, HE X L,WANG Y S,et al.BoLA-Ⅰ gene expression in early development of bovine SCNT embryo[J].Chinese Journal of Veterinary Science,2015,35(1):103-108.(in Chinese)
[11] 田知利,陈杰,胡江,等.牦牛和普通牛DRB1*intron1-exon2序列变异分析[J].华北农学报,2016,31(3):72-79. TIAN Z L,CHEN J,HU J,et al.Sequence variation at BoLA-DRB1* intron 1-exon 2 in yak and cattle[J].Acta Agriculturae Boreali-Sinica,2016,31(3):72-79.(in Chinese)
[12] AARESTRUP F M,JENSEN N E,OSTERGARD H.Analysis of associations between major histocompatibility complex (BoLA) class Ⅰ haplotypes and subclinical mastitis of dairy cows[J].Dairy Science,1995,78(8):1684-1692.
[13] MAILLARD J C,BERTHIER D,CHANTAL I,et al.Selection assisted by a BoLA-DR/DQ haplotype against susceptibility to bovine dermatophilosis[J].Genetics Selection Evolution,2003,35(Suppl 1):193-200.
[14] ALIZADEH Z,KARROW N,MALLARD B A.Biological effect of varying peptide binding affinity to the BoLA-DRB3*2703 allele[J].Genetics Selection Evolution,2003,35(Suppl 1):51-65.
[15] EIJK M J,STEWART-HAYNES J A, BEEVER J E,et al.Development of persistent lymphocytosis in cattle is closely associated with DRB2[J].Immunogenetics,1992;37(1):64-68.
[16] FENG J,LI Y,HASHAD M,et al.Bovine natural resistance associated macrophage protein 1(Nramp1) gene[J].Genome Research,1996,6(10):956-964.
[17] FORBES J R,GROS P.Iron,manganese,and cobalt transport by Nramp1(Slc11a1) and Nramp2(Slc11a2) expressed at the plasma membrane[J].Blood,2003,102(5):1884-1892.
[18] MARTINEZ R,TORO R,MONTOYA F,et al.Bovine SLC11A13' UTR SSCP genotype evaluated by a macrophage in vitro killing assay employing a Brucella abortus strain[J].Journal of Animal Breeding and Genetics.2008,125(4):271-279.
[19] 罗兴,尹立林,刘飞,等.BCL10、Nramp1基因多态性与大白仔猪断奶前腹泻关联分析[J].华中农业大学学报,2017,36(4):83-89. LUO X,YIN L L,LIU F,et al.Association between polymorphism of BCL10,Nramp1 genes and diarrhea traits in Large White piglets before weaning[J].Journal of Huazhong Agricultural University,2017, 36(4):83-89.(in Chinese)
[20] 戴超辉,吴嘉韵,孙丽,等.大肠杆菌刺激猪肠上皮细胞后Nramp1基因的表达变化分析[J].中国畜牧杂志, 2017,53(6):40-43. DAI C H,WU J Y,SUN L,et al.Analysis of the expression changes of Nramp1 gene in pig intestines epithelial cells stimulated by Escherichia coli[J].Chinese Journal of Animal Science,2017,53(6):40-43.(in Chinese)
[21] 郑王山,程箫,赵生国.藏猪天然抗性相关巨噬细胞蛋白基因克隆及变异研究[J].畜牧兽医杂志,2015,34(6):1-6. ZHENG W S,CHENG X,ZHAO S G.Research on clone and mutation of Nramp1 gene in Tibetan pig[J].Journal of Animal Science and Veterinary Medicine,2015,34(6):1-6.(in Chinese)
[22] 王洪梅,张利博,侯明海,等.牛Nramp1基因启动子的克隆及其活性分析[J].中国农业科学,2011,44(5):1022-1028. WANG H M, ZHANG L B, HOU M H,et al.Cloning and activity analysis of bovine natural resistance associated macrophage protein 1(Nramp1) gene promoter[J].Scientia Agricultura Sinica,2011,44(5):1022-1028.(in Chinese)
[23] 宁素恒,徐军,马生虎,等.宁夏地区荷斯坦牛Nramp1基因多态性分析[J].中国奶牛,2015,17:24-27. NING S H,XU J,MA S H,et al.Polymorphism of the Nramp1 gene of Holstein in Ningxia area[J].China Dairy Cattle,2015,17:24-27.(in Chinese)
[24] 张丽,刘丽霞,陈红,等.中国荷斯坦奶牛Nramp1基因多态性与泌乳性状及产奶量的关联性分析[J].浙江农业学报,2017,29(3):389-394. ZHANG L,LIU L X,CHEN H,et al.Genetic polymorphism of Nramp1 gene and its associations with milk traits and milk yield in Chinese Holstein cattle[J].Acta Agriculturae Zhejiangensis,2017,29(3):389-394.(in Chinese)
[25] CHENG X,YU X,LIU Y,et al.Functional analysis of bovine Nramp1 and production of transgenic cloned embryos in vitro[J].Zygote,2015,23(1):83-92.
[26] GADJEVA M,TAKAHASHI K,THIEL S.Mannan-binding lectin——A soluble pattern recognition molecule[J].Molecular Immunology,2004,41(2-3):113-121.
[27] IP W K,TAKAHASHI K,EZEKOWITZ R A,et al.Mannose-binding lectin and innate immunity[J].Immunological Reviews,2009,230(1):9-21.
[28] 吕晓锋.利用巴斯德毕赤酵母表达重组中国水仙凝集素的发酵工艺研究[D].北京:北京化工大学,2014. LV X F.The fermentation and expression of NTL,a lectin from Chinese narcissus (recombinant narcissus tazetta var.Chinensis roem),in the yeast Pichia pastoris[D].Beijing:Beijing University of Chemical Technology,2014.(in Chinese)
[29] KILPATRICK D C.Mannan-binding lectin and its role in innate immunity[J].Transfusion Medicine and Hemotherapy,2002,12(6):335-352.
[30] WANG X,JU Z,HUANG J,et al.The relationship between the variants of the bovine MBL2 gene and milk production traits,mastitis,serum MBL-C levels and complement[J].Veterinarg Immunology Immunopathology,2012,148(3-4):311-319.
[31] 白井岩,吴洁,蒋小强,等.公牛MBL2基因多态性与精液品质及后裔生产性能的相关性研究[J].畜牧兽医学报,2013,44(10):1561-1568. BAI J Y,WU J,JIANG X Q,et al.Association of polymorphisms of MBL2 gene with semen quality and progeny performance of bulls[J].Chinese Journal of Animal and Veterinary Sciences,2013,44(10):1561-1568.(in Chinese)
[32] CAPPARELLI R,PARLATO M,AMOROSO M G,et al.Mannose-binding lectin haplotypes influence Brucella abortus infection in the water buffalo(Bubalus bubalis)[J].Immunogenetics,2008,60(3-4):157-165.
[33] 许超, 彭科,王文生,等.甘露糖结合凝集素对肠上皮细胞凋亡的调控作用及机制研究[J].局解手术学杂志,2015,24(3):237-241. XU C,PENG K,WANG W S,et al.Research on the function and mechanism of mannose-binding lectin regulating intestinal epithelial apoptosis[J].Journal of Regional Anatomy and Operative Surgery,2015,24(3):237-241.(in Chinese)
[34] 刘洋,郭艳玲,姜广路,等.甘露糖结合凝集素水平的调节与肺结核易感性关系的研究[J].国际检验医学杂志,2016,37(13):1767-1769. LIU Y,GUO Y L,JIANG G L,et al.Study on relation between regulation of MBL level and pulmonary tuberculosis susceptibility[J].Journal of Clinical Pulmonary Medicine, 2016,37(13):1767-1769.(in Chinese)
[35] MEDZHITOV R.Toll-like receptors and innate immunity[J].Nature Reviews Immunology,2001,1(2):135-145.
[36] 曹随忠,李计尚,张于,等.TLRs基因在牦牛雄性生殖器官中表达情况的检测[J].中国兽医科学,2014,44(2):193-198. CAO S Z,LI J S,ZHANG Y,et al.Expression profile of TLRs gene in the reproductive organs of male Bos grunniens[J].Chinese Veterinary Science,2014,44(2):193-198.(in Chinese)
[37] 林宝山,兰道亮,陈亚冰,等.麦洼牦牛TLR1~10基因克隆及分子生物学特征分析[J].畜牧兽医学报,2015, 46(5):728-737. LIN B S,LAN D L,CHEN Y B, et al.Molecular cloning and biological characterization analysis of Toll-like receptors 1-10 in Maiwa yak[J].Chinese Journal of Animal and Veterinary Sciences,2015,46(5):728-737.(in Chinese)
[38] 林宝山,兰道亮,黄偲,等.牦牛TLR2和TLR4基因mRNA在不同组织中的表达分布研究[J].中国预防兽医学报,2014,36(11):901-903. LIN B S,LAN D L,HUANG C,et al.The mRNA expressions of TLR2 and TLR4 genes in different yak tissues[J].Chinese Journal of Preventive Veterinary Medicine,2014,36(11):901-903.(in Chinese)
[39] 陈仁金,王珍珍,杨章平,等.中国荷斯坦牛Toll样受体4基因的遗传多态性与体细胞评分的关联分析[J].中国畜牧兽医,2013,40(11):134-138. CHEN R J,WANG Z Z,YANG Z P,et al.Genetic polymorphism of TLR4 gene and its associations with somatic cell score in Chinese Holstein cattle[J].China Animal Husbandry & Veterinary Medicine, 2013,40(11):134-138.(in Chinese)
[40] DANIEL R,HISAKO F,SHUANG X U,et al.Elevated CD14(cluster of differentiation 14) and toll-like receptor (TLR) 4 signaling deteriorate periapical inflammation in TLR2 deficient mice[J].Anatomical Record (Hoboken),2016,299(9):1281-1292.
[41] 林宝山,兰道亮,黄偲,等.牦牛TLR6基因的克隆、序列分析及其表达分布研究[J].东北农业大学学报,2014, 45(7):91-97. LIN B S,LAN D L,HUANG C,et al.Cloning,sequence analysis of TLR6 gene of yak and expression and distribution in tissues[J].Journal of Northeast Agricultural University,2014,45(7):91-97.(in Chinese)
[42] 林宝山,兰道亮,陈亚冰,等.牦牛TLR7基因的克隆序列分析及其组织表达研究[J].中国畜牧杂志,2014,50(19):10-16. LIN B S,LAN D L,CHEN Y B,et al.Cloning and sequence analysis of TLR7 gene and its expression and distribution in tissues of yak[J].Chinese Journal of Animal Science,2014,50(19):10-16.(in Chinese)
[43] FARIAS M V,LENDEZ P A,MARIN M,et al.Toll-like receptors,IFN-γ and IL-12 expression in bovine leukemia virus-infected animals with low or high proviral load[J].Research in Veterinary Science,2016,107:190-195.
[44] 陈亚冰,兰道亮,林宝山,等.牦牛Toll样受体5基因的克隆及序列分析[J].中国畜牧兽医,2014,41(7):30-34. CHEN Y B,LAN D L,LIN B S,et al.Cloning and sequence analysis of TLR5 gene from yak[J].China Animal Husbandry & Veterinary Medicine,2014,41(7):30-34.(in Chinese)
[45] 吴语宁,丛凡淏.牛主要抗病候选基因的研究进展[J].吉林农业,2013,2:282-283. WU Y N,CONG F H.Advances in research on genes of major resistance genes for cattle[J].Jilin Agriculture,2013,2:282-283.(in Chinese)
[46] 熊辉,付丽萍,周琳.干扰素对肿瘤的抑制作用[J].华中科技大学学报(医学版),2014,43(5):599-602. XIONG H,FU L P,ZHOU L.Inhibitory effect of interferon on tumor[J].Acta Medicinae Universitatis Scientiae et Technologiae Huazhong,2014,43(5):599-602.(in Chinese)
[47] 宋灵俊.鸡干扰素基因突变与其抗马立克病的相关性分析[D].泰安:山东农业大学,2013. SONG L J.Correlation between mutations of chicken interferon and resistance to Marek's disease[D].Tai'an:Shandong Agricultural University,2013.(in Chinese)
[48] 徐晶晶.噬菌体展示肽与单克隆抗体分析牛IFN-γ的抗病毒活性位点[D].哈尔滨:东北农业大学, 2013. XU J J.Analyse the sextion of the antiviral activity of the bovine IFN-γ by the phage display peptide and monoclonal antibody[D].Harbin:Northeast Agricultural University,2013.(in Chinese)
[49] 李树启,赵俊,王利利,等.水牛干扰素α的可溶性原核表达、纯化及其抗病毒活性[J].中国生物制品学杂志,2017,30(3):272-277. LI S Q,ZHAO J,WANG L L,et al.Soluble prokaryotic expression,purification and antiviral activity of recombinant bovine interferon α[J].Chinese Journal of Biologicals,2017,30(3):272-277.(in Chinese)
[50] 蔡进忠,史喜菊,李少勇,等.牦牛IFN-α基因的克隆表达及抗病毒活性研究[J].中国兽医杂志,2006,10:3-6. CAI J Z, SHI X J,LI S Y,et al.Cloning and expression of IFN-α gene of yak and its effect on antiviral activities[J].Chinese Journal of Veterinary Medicine,2006,10:3-6.(in Chinese)
[51] 彭统全,邵建伟,张润祥,等.牛α0干扰素在毕赤酵母中的分泌表达及抗病毒活性鉴定[J].畜牧兽医学报,2015,46(1):124-129. PENG T Q,SHAO J W,ZHANG R X,et al.Expression of the bovine interferon Alpha0 with antiviral activity in Pichia pastoris[J].Chinese Journal of Animal and Veterinary Sciences,2015,46(1):124-129.(in Chinese)
[52] 孙俊若男,李海明,苏韵,等.IFN-γ对奶牛乳腺上皮细胞转分化的影响[J].安徽农业科学,2017,45(4):99-101. SUN J R N,LI H M,SU Y,et al.Effects of interferon-γ (IFN-γ) on the trans differentiation of mammary epithelial cells in dairy cows[J].Journal of Anhui Agricultural Sciences,2017,45(4):99-101.(in Chinese)
[53] UEHARA J,OHKURI T,KOSAKA A,et al.Intratumoral injection of IFN-β induces chemokine production in melanoma and augments the therapeutic efficacy of anti-PD-L1 mAb[J].Biochemical and BiophysicalResearch Communications,2017, 490(2):521-527.
[54] LI Q,YAN Z,LI F,et al.The improving effects on hepatic fibrosis of interferon-γ liposomes targeted to hepatic stellate cells[J].Nanotechnology,2012,23(26):265101.
[55] 刘秀,胡江,罗玉柱.藏绵羊基因OLA-DQA2第2外显子多态性分析[J].中国农业科学,2009,42(8):2930-2936. LIU X,HU J,LUO Y Z.Polymorphisms of the gene OLA-DQA2 exon 2 in Tibetan sheep[J].Scientia Agricultura Sinica,2009,42(8):2930-2936.(in Chinese)
[56] SINGH P K,SINGH S V,SINGH M K,et al.Effect of genetic variation in the MHC class Ⅱ DRB region on resistance and susceptibility to Johne's disease in endangered Indian Jamunapari goats[J].International Journal of Immunogenetics,2012,39(4):314-320.