蒙古马胰岛素样生长因子I（IGF-I）多态性分析
摘要
胰岛素样生长因子Ⅰ(Insulin-like growth factor-Ⅰ)是近年来在家畜遗传育种中被广泛关注的候选基因之一。它与家畜的生长发育有着密切的关系。但国内外关于该基因是否影响中国蒙古马生长发育的研究开展却较少。本课题通过PCR-SSCP技术、PCR-RFLP技术对四个类型的地方品种中国蒙古马及引入品种纯血马、培育品种三河马共277个样品的胰岛素样生长因子Ⅰ基因的3′,5′端两个侧翼区及第三、四两个外显子进行了多态性进行了检测和序列比较分析,得出以下结论:
(1)通过PCR-SSCP检测,在马的IGF-I第3、第4外显子区域,未检测到多态位点。但在IGF-Ⅰ基因3′侧翼区检测到多态位点,检测到AA、AB、BB三种基因型。并且该三种基因型和马的体尺指标具有相关性。
(2)通过PCR-RFLP分析,采用3种限制性内切酶BsmaⅠ、DraⅠ、BamhⅠ进行酶切,在IGF-Ⅰ基因5′侧翼区并没有检测到多态位点。可能原因是所选择的酶恰好没有检测到,另外IGF-Ⅰ基因5′侧翼区序列相当保守。因此,此位点是否调控马的生长发育还需要进一步深入的研究。
(3)不同类群马IGF-Ⅰ基因3′侧翼区位点的遗传信息参数分析结果表明:纯血马多态信息含量最高为0.589,乌审马最低为0.432,此位点遗传信息参数可能为马的分子遗传育种提供理论基础。
Recently, Insulin-like growth factor-I is one of the most famous gene in heredity breeding area, which has nearly relationship with domestic animal growth. However, just a few researches that the gene how to modulate the development of Chinese Mongolia horse has been done. In this work, we used the methods of PCR-SSCP and PCR-RFLP, aligned the 3'and 5' end flanking and 3rd and 4th exon sequence of IGF-I from 277 house samples(including 4 kinds of Chinese Mongolia house, TB house and breeded SH horse)and analyzing the gene polymorphisms, the results can be listed as follows :
1) According to the PCR-SSCP result, the sequence of 3rd and 4th exon is more conserved than polymorphic. Analysis genotype and gene frequency of the IGF-I 3'end flanking, we found AA, AB and BB genotypes. These genotypes is concerned with the index of body size.
2)During the PCR-RFLP analysis, we used BsmaI, DraI and BamHI restriction enzymes to examine the 5'end flanking polymorphisms and no difference was found. The reason may be that the restriction enzymes was not suitable. Therefore, whether the IGF-I 5'end flanking regulate house growth or not, we are still not sure.
3) The analysis result of the polymorphism information content (PIC) of IGF-I 3'end flanking indicated that: SH horse has highest (0.589), WS horse has lowest polymorphism information conten(t0.432). The genetic information of this site could be a basic theory for horse molecular genetic breeding..
(1)通过PCR-SSCP检测,在马的IGF-I第3、第4外显子区域,未检测到多态位点。但在IGF-Ⅰ基因3′侧翼区检测到多态位点,检测到AA、AB、BB三种基因型。并且该三种基因型和马的体尺指标具有相关性。
(2)通过PCR-RFLP分析,采用3种限制性内切酶BsmaⅠ、DraⅠ、BamhⅠ进行酶切,在IGF-Ⅰ基因5′侧翼区并没有检测到多态位点。可能原因是所选择的酶恰好没有检测到,另外IGF-Ⅰ基因5′侧翼区序列相当保守。因此,此位点是否调控马的生长发育还需要进一步深入的研究。
(3)不同类群马IGF-Ⅰ基因3′侧翼区位点的遗传信息参数分析结果表明:纯血马多态信息含量最高为0.589,乌审马最低为0.432,此位点遗传信息参数可能为马的分子遗传育种提供理论基础。
Recently, Insulin-like growth factor-I is one of the most famous gene in heredity breeding area, which has nearly relationship with domestic animal growth. However, just a few researches that the gene how to modulate the development of Chinese Mongolia horse has been done. In this work, we used the methods of PCR-SSCP and PCR-RFLP, aligned the 3'and 5' end flanking and 3rd and 4th exon sequence of IGF-I from 277 house samples(including 4 kinds of Chinese Mongolia house, TB house and breeded SH horse)and analyzing the gene polymorphisms, the results can be listed as follows :
1) According to the PCR-SSCP result, the sequence of 3rd and 4th exon is more conserved than polymorphic. Analysis genotype and gene frequency of the IGF-I 3'end flanking, we found AA, AB and BB genotypes. These genotypes is concerned with the index of body size.
2)During the PCR-RFLP analysis, we used BsmaI, DraI and BamHI restriction enzymes to examine the 5'end flanking polymorphisms and no difference was found. The reason may be that the restriction enzymes was not suitable. Therefore, whether the IGF-I 5'end flanking regulate house growth or not, we are still not sure.
3) The analysis result of the polymorphism information content (PIC) of IGF-I 3'end flanking indicated that: SH horse has highest (0.589), WS horse has lowest polymorphism information conten(t0.432). The genetic information of this site could be a basic theory for horse molecular genetic breeding..
引文
1 HAN Guo-Cai, ZHAO Chun-Jiang, WU Ke-Liang. NatureDevelopment Factors of Chinese Modern Horse Industry.Anthology of Modern Horse Industry. Beijing: China AgriculturalScience and Technology Press, 2007.韩国才,赵春江,吴克亮.中国现代马业发展因素的培育.现代马业选集.北京:中国农业科学技术出版社, 2007.
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3侯文通.东南亚小型马来源的遗传学和历史学研究.西北农业大学学报,1994,22(1):7-12
4侯文通,李湘运.西南马的遗传分化及若干地方类型亲缘关系的研极.西北农业学报,1993,4:98-102
5侯文通,孙超.南亚小型马近缘关系的研究.西北农业学报,1995,23(5)23-28
6史宪伟等.云南四个马品种的随机扩增多态DNA(RAPD)分析.牧兽医学报,1998,29(3):193-203
7芒来,李金莲.中国蒙古马与国外纯血马mtDNA D-Loop高变区序列比较.遗传,2005,27(1):145-150
8李金莲,芒来.利用微卫星标记对蒙古马和纯血马遗传多样性的研究.畜牧兽医学报,2005,36:
6-9
9 ZHANG Yan-Ru, WU Ni-Erfu, Manglai. Study on cloningand sequence analysis of growth hormone gene in Mongolianhorse. Chinese Journal of Animal Science, 2006,42(9): 10-12.
10 ZHANG Yan-Ru, MENG Qing-Long, MANG-Lai. Analysisof horse growth hormone (GH) gene by PCR-RFLP.Journal of Inner Mongolia Agricultural University, 2006,27(2): 1-4.
11 ZHANG Yan-Ru. Study on sequences, molecular evolutionand polymorphism of horse growth hormone gene [Dissertation].Huhhot: Inner Mongolia Agricultural University, 2005.
12范彩云,芒来,森裕司.马DRD4基因部分序列的克隆及StyⅠ酶切多态性分析[J]黑龙江畜牧兽医, 2007,(09) .17-19.
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19 Raschdorf F, Dahinden R,MaerkiW, et al. Location of DisulphideBonds In Human Insulin - like Growth Factors ( Igfs) Synthesizedby Recombinant Dna Technology. Biomed Environ Mass Spectrom,1988, 16 (1 - 12) : 3～8
20 Elliott S, Fagin KD,NarhiL O, et al. Yeast - derived RecombinantHuman Insulin -like Growth Factor I: Production, Purification,and Structural Characterization. J Protein Chem, 1990, 9 ( 1) : 95～104
21 Hober S, Forsberg G, Palm G, et al. Disulfide Exchange Folding ofInsulin - like Growth Factor I. Biochemistry, 1992, 31 ( 6) : 1749～1756
22 Narhi L O, Hua Q X, Arakawa T, et al. Role of Native DisulfideBonds In the Structure and Activity of Insulin - like Growth Factor1: GeneticModels of Protein - folding Intermediates. Biochemistry,1993, 32 (19) : 5214～5221
23 Hober S,UhlenM,Nilsson B. Disulfide Exchange Folding of Disul2fideMutants of Insulin - like Growth Factor I In Vitro. Biochemis2try, 1997, 36 (15) : 4616～4622
24 Hober S, Lundstrom L J,UhlenM, et al. Insulin - like Growth Fac2tors I and Ii are Unable to Form andMaintain theirNative DisulfidesUnder In Vivo Redox Conditions. FEBS Lett, 1999, 443 ( 3) : 271～276
25 Cooke R M, Harvey T S, Campbell ID. Solution Structure of HumanInsulin - like Growth Factor 1: a NuclearMagnetic Resonance andRestrainedMolecularDynamics Study. Biochemistry, 1991, 30 (22) :5484～5491
26 Sato A, Koyama S, Yamada H, et al. Three - dimensional SolutionStructure of a Disulfide Bond Isomer of the Human Insulin - likeGrowth Factor - i. J Pep t Res, 2000, 56 (4) : 218～230
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2 National Bureau of Statistics of China. China StatisticalYearbook(2006). Beijing: China Statistics Press, 2006, 485.中华人民共和国国家统计局.中国统计年鉴(2006).北京:中国统计出版社, 2006, 485.
3侯文通.东南亚小型马来源的遗传学和历史学研究.西北农业大学学报,1994,22(1):7-12
4侯文通,李湘运.西南马的遗传分化及若干地方类型亲缘关系的研极.西北农业学报,1993,4:98-102
5侯文通,孙超.南亚小型马近缘关系的研究.西北农业学报,1995,23(5)23-28
6史宪伟等.云南四个马品种的随机扩增多态DNA(RAPD)分析.牧兽医学报,1998,29(3):193-203
7芒来,李金莲.中国蒙古马与国外纯血马mtDNA D-Loop高变区序列比较.遗传,2005,27(1):145-150
8李金莲,芒来.利用微卫星标记对蒙古马和纯血马遗传多样性的研究.畜牧兽医学报,2005,36:
6-9
9 ZHANG Yan-Ru, WU Ni-Erfu, Manglai. Study on cloningand sequence analysis of growth hormone gene in Mongolianhorse. Chinese Journal of Animal Science, 2006,42(9): 10-12.
10 ZHANG Yan-Ru, MENG Qing-Long, MANG-Lai. Analysisof horse growth hormone (GH) gene by PCR-RFLP.Journal of Inner Mongolia Agricultural University, 2006,27(2): 1-4.
11 ZHANG Yan-Ru. Study on sequences, molecular evolutionand polymorphism of horse growth hormone gene [Dissertation].Huhhot: Inner Mongolia Agricultural University, 2005.
12范彩云,芒来,森裕司.马DRD4基因部分序列的克隆及StyⅠ酶切多态性分析[J]黑龙江畜牧兽医, 2007,(09) .17-19.
13 SambrookJ,FritschEF,MnaiatisT.MoLecular cloning:a laboratory manual.1989,Second Edition .New York :Cold Spring Harbor Laboratory Press.
14李会成,李文辉等,基因工程菌的发醉研究,生物工程进展,1997,17(3):40-43
15 Georgious G,Valax P.Expression of correctly folded proteins in E. coli’.Curr Opin Biotechnol,1996,7(2):190-197.
16 Humbel R E, Insulin - like Growth Factors I and Ii. Eur J Biochem,1990, 190 (3) : 445～462
17 Sato A, Koyama S, Yamada H, et al. Three - dimensional SolutionStructure of a Disulfide Bond Isomer of the Human Insulin - likeGrowth Factor - i. J Pep t Res, 2000, 56 (4) : 218～230 :
18 Cooke R M, Harvey T S, Campbell ID. Solution Structure of HumanInsulin - like Growth Factor 1: a NuclearMagnetic Resonance andRestrainedMolecularDynamics Study. Biochemistry, 1991, 30 (22) :5484～5491
19 Raschdorf F, Dahinden R,MaerkiW, et al. Location of DisulphideBonds In Human Insulin - like Growth Factors ( Igfs) Synthesizedby Recombinant Dna Technology. Biomed Environ Mass Spectrom,1988, 16 (1 - 12) : 3～8
20 Elliott S, Fagin KD,NarhiL O, et al. Yeast - derived RecombinantHuman Insulin -like Growth Factor I: Production, Purification,and Structural Characterization. J Protein Chem, 1990, 9 ( 1) : 95～104
21 Hober S, Forsberg G, Palm G, et al. Disulfide Exchange Folding ofInsulin - like Growth Factor I. Biochemistry, 1992, 31 ( 6) : 1749～1756
22 Narhi L O, Hua Q X, Arakawa T, et al. Role of Native DisulfideBonds In the Structure and Activity of Insulin - like Growth Factor1: GeneticModels of Protein - folding Intermediates. Biochemistry,1993, 32 (19) : 5214～5221
23 Hober S,UhlenM,Nilsson B. Disulfide Exchange Folding of Disul2fideMutants of Insulin - like Growth Factor I In Vitro. Biochemis2try, 1997, 36 (15) : 4616～4622
24 Hober S, Lundstrom L J,UhlenM, et al. Insulin - like Growth Fac2tors I and Ii are Unable to Form andMaintain theirNative DisulfidesUnder In Vivo Redox Conditions. FEBS Lett, 1999, 443 ( 3) : 271～276
25 Cooke R M, Harvey T S, Campbell ID. Solution Structure of HumanInsulin - like Growth Factor 1: a NuclearMagnetic Resonance andRestrainedMolecularDynamics Study. Biochemistry, 1991, 30 (22) :5484～5491
26 Sato A, Koyama S, Yamada H, et al. Three - dimensional SolutionStructure of a Disulfide Bond Isomer of the Human Insulin - likeGrowth Factor - i. J Pep t Res, 2000, 56 (4) : 218～230
27 Gerrard D E, Okamura C S, and Grant A L. (1999). Expression and location of IGF bindingproteins-2, -4, and -5 in developing fetal tissue. Journal of Animal Science. 77: 1431-1441
28 Gatord K L, Fletcher T P, Clarke I J, Owens P C, Quinn K J, Walton P E, Grant P A, Hosking B J,Egan A R,and Ponnanpalam E N.(1996).Sexual dimorphism of circulating somatotropin,insulin-like growth factor-1 and 2, insulin-like growth factor binding proteins, and insulin:Relationships to growth rate and carcass characteristics in growing lambs.Journal of AnimalScience. 74: 1314-1325
29 GrimesR W, and Hammond J M.(1992b). Insulin and insulin-like growth factors(IGFs) stimulateproduction of IGF-binding proteins by ovarian granulosa cells. Endocrinology.131:553～558
30 Kanatani M, Sugimoto T , Kano J , et al . IGF-Ⅰmediates the stimulato- ry effect of high phosphate concentration on osteoblastic cell prolifera2tion. J Cell Physiol ,2002 ,190 :306-312.
31 Sakata T , Halloran BP , Elalieh HZ , et al . Skeletal unloading inducesresistance to insulin-like growth factorⅠon bone formation. Bone ,2003 ,32 :669-680.
32 Farley JR , Stilt-Coffing B. Apoptosis may determine the release ofskeletal alkaline phosphatase activity from human osteoblast2line cells.Calcif Tissue Int ,2001 ,68 :43-52.
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