新疆策勒黑羊和多浪羊多胎候选基因的研究
|
摘要
本研究以BMPR-IB基因,BMP15基因,GDF9基因和ESR基因为多胎候选主效基因,分别对策勒黑羊(167只),多浪羊(49只)进行了分析研究,结果表明,策勒黑羊和多浪羊均存在BMPR-IB基因的746单碱基A-G突变。策勒黑羊中三种基因型纯合子(BB)、杂合子(B+)、野生型(++)的频率分别是0.10(17)、0.35(58)和0.55(91),产羔数与基因型之间的分析结果表明,三种基因型之间的产羔数差异显著,其中++型和B+差异显著(p<0.05);++型和BB差异极显著(p<0.01)。策勒黑羊上没有检测到BMP15基因突变(FecXG、FecXB、FecXI、FecXH)和GDF9基因突变(FecGH),策勒黑羊ESR基因的第一外显子发生一个点突变(C-G突变),突变纯合子(EE)、杂合子(E+)和野生型(++)基因型频率分别是0.03(5 )、0.31(52)和0.66(110);对ESR基因型和策勒黑羊产羔数分析结果表明,策勒羊三种基因型之间产羔数差异显著,其中++型和EE差异显著(p<0.05)。通过BMPR-IB基因和ESR基因叠加效应分析表明,同时存在两种基因突变的个体的产羔数没有变化。
从多浪羊460只样本中,检测到BMPR-IB的突变基因,++、B+频率分别为0.94和0.06,没有发现BB型个体,多浪羊(49只)没有发现BMP15基因和GDF9基因突变。
通过上述研究,确定在新疆多浪羊和策勒黑羊中存在多胎主效基因BMPR-IB基因突变,策勒黑羊中还存在ESR基因突变,为今后在多浪羊和策勒黑羊中进行标记辅助选择奠定了分子生物学基础。
根据点突变扩增的特点,结合国内外研究,建立了实验室大批量检测突变标记位点的Tetra-ARMS PCR技术,并对多浪羊460和策勒黑羊167个样本进行了检测,并与PCR-RFLP结果进行了对比,结果表明该技术有方便、快速、经济等优点,结果可靠,适合推广应用。
BMPR-IB gene as a fecundity candidate gene was studied in Cele black sheep(167 blood samples) and Duolang sheep(509) by Tetra-primer ARMS-PCR technique. The results showed that there was a mutation (A746G) of BMPR-IB gene in Cele black sheep and Duolang sheep, between them, the BB、B+ and ++ frequence in Cele black sheep were 0.10、0.35 and 0.55 respectively. There was no BB genetype in detected Duolang sheep, and the B+、++ frequence were 0.06 and 0.94 respectively. Analyzing the association with litter size showed that, Cele black sheep with genotype BB had a most significantly difference litter size than those with genotype ++ (P<0.01); B+ had a significantly difference litter size than those with genotype ++ (P<0.05); BMPR-IB gene was a major gene influencing prolificacy in Cele black sheep; the Tetra-primer ARMS-PCR technique was simple,rapid and economical for detecting BMPR-IB mutation and other SNP locus.
BMP15 and GDF9 as candidate gene of high fecundity were detected in Cele black sheep and Duolang sheep.No mutant genetypes were identified in FecG H lacus of GDF9 and FecXG、FecXB、FecXI、FecXH four locus of BMP15 .Our results suggested that BMP15 and GDF9 may not be the major gene for the high prolificity of Cele Black sheep and Duolang sheep.
ESR gene as a fecundity candidate gene was studied in Cele black sheep(44 blood samples), Duolang sheep(176), Hu sheep (31) and Small Tail Han sheep (33blood samples) by PCR-RFLP and PCR-SSCP technique. The results showed that there was a mutation (C363G) of exon 1 of ESR gene in Cele black sheep, Hu sheep and Small Tail Han sheep . Among them, the EE、E+ and ++ frequence in Cele black sheep were 0.03、0.31 and 0.66 respectively; the EE、E+ and ++ frequence in Hu sheep were 0.03、0.19 and 0.77 respectively. And the EE、E+ and ++ frequence in Small Tail Han sheep were 0.03、0.42 and 0.55 respectively. Analyzing the association with litter size showed that, Cele black sheep with genotype EE had a most significantly difference litter size than those with genotype ++ (P<0.05); ESR gene was a major gene influencing prolificacy in Cele black sheep.
从多浪羊460只样本中,检测到BMPR-IB的突变基因,++、B+频率分别为0.94和0.06,没有发现BB型个体,多浪羊(49只)没有发现BMP15基因和GDF9基因突变。
通过上述研究,确定在新疆多浪羊和策勒黑羊中存在多胎主效基因BMPR-IB基因突变,策勒黑羊中还存在ESR基因突变,为今后在多浪羊和策勒黑羊中进行标记辅助选择奠定了分子生物学基础。
根据点突变扩增的特点,结合国内外研究,建立了实验室大批量检测突变标记位点的Tetra-ARMS PCR技术,并对多浪羊460和策勒黑羊167个样本进行了检测,并与PCR-RFLP结果进行了对比,结果表明该技术有方便、快速、经济等优点,结果可靠,适合推广应用。
BMPR-IB gene as a fecundity candidate gene was studied in Cele black sheep(167 blood samples) and Duolang sheep(509) by Tetra-primer ARMS-PCR technique. The results showed that there was a mutation (A746G) of BMPR-IB gene in Cele black sheep and Duolang sheep, between them, the BB、B+ and ++ frequence in Cele black sheep were 0.10、0.35 and 0.55 respectively. There was no BB genetype in detected Duolang sheep, and the B+、++ frequence were 0.06 and 0.94 respectively. Analyzing the association with litter size showed that, Cele black sheep with genotype BB had a most significantly difference litter size than those with genotype ++ (P<0.01); B+ had a significantly difference litter size than those with genotype ++ (P<0.05); BMPR-IB gene was a major gene influencing prolificacy in Cele black sheep; the Tetra-primer ARMS-PCR technique was simple,rapid and economical for detecting BMPR-IB mutation and other SNP locus.
BMP15 and GDF9 as candidate gene of high fecundity were detected in Cele black sheep and Duolang sheep.No mutant genetypes were identified in FecG H lacus of GDF9 and FecXG、FecXB、FecXI、FecXH four locus of BMP15 .Our results suggested that BMP15 and GDF9 may not be the major gene for the high prolificity of Cele Black sheep and Duolang sheep.
ESR gene as a fecundity candidate gene was studied in Cele black sheep(44 blood samples), Duolang sheep(176), Hu sheep (31) and Small Tail Han sheep (33blood samples) by PCR-RFLP and PCR-SSCP technique. The results showed that there was a mutation (C363G) of exon 1 of ESR gene in Cele black sheep, Hu sheep and Small Tail Han sheep . Among them, the EE、E+ and ++ frequence in Cele black sheep were 0.03、0.31 and 0.66 respectively; the EE、E+ and ++ frequence in Hu sheep were 0.03、0.19 and 0.77 respectively. And the EE、E+ and ++ frequence in Small Tail Han sheep were 0.03、0.42 and 0.55 respectively. Analyzing the association with litter size showed that, Cele black sheep with genotype EE had a most significantly difference litter size than those with genotype ++ (P<0.05); ESR gene was a major gene influencing prolificacy in Cele black sheep.
引文
[1] Evans ACO,et al.〔J〕.Biology of reproduction,1997,57:394～401
[2] Fortune JE,et al.〔J〕.Biol0gy of reproduction,1994,50:225～232
[3] Diaz T et al. Human chorionic gonadotropin induced alterations inovarian follicular dynamics during the estrus cycle of heifers[J].J.Anim.Sci.1998,76: 1929～1936
[4] 雪雪芹. 牛、羊多胎性状的 DNA 分子标记研究[D].学位论文.2002.陕西
[5] Hould, A. et a1.(1994) Structure of the bovine follicle- stimulating hormone receptor complementary DNA and expression in bovine tissues. Mol. Reprod. Dev. 39:127-135.
[6] Heckert, L.L., Daley, LJ. and Griswold, M. (1992) Structure rganization of the follicle-stimulating hormone receptor gene Mo1.CelLEndocrino1.1992, 6:70-80.
[7] Snyder , D.A (1986) Superovulation of cows and heifers selected for twinning. Theriogenology.25:200.
[8] indon, B.M.et al. (1986)Genetic and hormonal factors affecting Superovulation . Theriogenology. 25(1): 53-70
[9] 毕晓丹 小尾寒羊高繁殖力候选基因 ESR 的研究(M),学位论文 2005,吉林 延吉
[10] 吴常信,张伯洪.动物遗传育种学总论(主编:张沅).北京:北京农业大学出版社,1996.225
[11] COGNOSAG/Standard ised Genetic Bomenclature for Sheep and Goat.Lavoisier, Paris,1989
[12] McNatty K P, Hudson N, Henderson K M, et al. Differences in gonadotrophin concentrations and pituitary responsiveness to GnRH between Booroola ewes which were homozygous (FF) , heterozygous (F+) and non~carriers (++) of a major gene influencing their ovulation rate. J.Repro.Fert..,1987,80:577~588.
[13] Mcnatty, K.P., Hudson, N.L., Shaw, L., et al. Plasma concentrations of FSH, LH, thyroid~stimulating hormone and growth hormone after exogenous stimulation with GnRH, TRH and GHRH in Booroola ewes that are homozygous carriers or non~ carriers of the Fec(B) gene. Journal of Reproduction and Fertility .1994,102: 177~183.
[14] McNatty,K.P.etal.In:Major Gene for Reproductionin Sheep . Eds, J-Melsen , L.Bodin&J . Thimonier. Institute National edela Recherche,Agronomique, Paris.199IB.105~ 124.
[15] Cummins, L.J.etal[J]. Repro.Ferti,1983,67:1~7
[16] Mulsant P,Lecerf F,Fabre S,Setal. Mutation in Bone morphogenetic protein receptor~IB is associated with increased ovulation rate in Booroola Merino ewes. proceedings of the National Academy of Sciences of the USA,2001,98: 5104~ 5109.
[17] Wilson T,Wu X Y, Juenge I J etal.Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of Bone morphogenetic protein IB receptor(ALK~6) that is expressed in Both oocytes and granulosa cells. Biology of Reproduction. 2001, 64:1225~ 1235.
[18]Mulsant P,Lecerf F,Fabre S, et al. Mutation in Bone morphogenetic protein receptor~IB is associatedwith increased ovulation rate in Booroola Merino ewes. proceedings of the National Academy of Sciences of the USA,2001,98: 5104~ 5109.
[19] Souza C J, Campbell BK, McNeilly A S, et al. The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPRIB). J Endocrinol. 2001,169(2):Rl~R6.
[20] Liu F, Ventura F, Doody J, et al. Human type II receptor for bone morphogenic proteins (BMPs): extension of the two~kinase receptor model to the BMPs. Mol Cell Biol ,1995, 15(7):3479~3486.
[21] Attisano L,Wrana J L,Montalvo E,et al.Activation of signal in by the activin receptor complex.Mol Cell Biol, 1996, 16:1066~1073.
[22] Fujii M, Takeda K, Imamura T, Aoki H, Sampath T K, Enomoto S, Kawabata M, Kato M, Ichijo H, Miyazono K. Roles of bone morphogenetic protein type Ireceptors and Smad proteins in osteoblast and chondroblast differentiation[J]. Mol BiolCell ,1999, 10(11): 3801~3813.
[23] Mishina Y, Suzuki A, Gilbert D J, Copeland N G, Jenkins N A, Ueno N, Behringer R R. Genomic organization and chromosomal location of the mouse type I BMP-2/4 receptor[J]. Biochem Biophys Res Commun, 1995, 206(1):310~317
[24] Hayashi K. PCR-SSCP:A simple and sensitive method for detection of mutation in the genomic DNA[J]. PCR Methods Appl, 1991, 1:34～38.
[25] Larsen,N J, Nielsen V H. Apa I and Cfo I polymorphisms in the porcine growth hormone gene[J]. Animal Genetics, 1993, 24(1):71~76
[26] 闫亚东,曾勇庆,储明星. 小尾寒羊 BMPR-IB 基因单核苷酸多态性及其与产羔性能关系的研究[M].学位论文 2004.山东
[27] 钟发刚等,绵羊多胎性状分子标记辅助选择技术研究[M].学位论文.2004 石河子
[28] 刘淑芳 小尾寒羊多胎性状相关基因的鉴定与研究[D].学位论文.2004.山东
[29] 贾存灵 小尾寒羊多胎性状主要侯选基因及繁殖相关基因表达量研究[D].学位论文 2005 北京
[30] Hanrahan P ,l, Gregan S M, Mulsant P, Mullen M, Davis G H, Powcll R.Galloway S M. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belelare sheep (Ovis aries) [J]. Bio1 Reprod, 2004.70(4):900~909.
[31] Sadighi M, Bodensteiuer K J, Beattie A E, Galloway S M. Genetic mapping of ovine growth differentiation factor 9 (GDF9) to sheep chromosome 5[J]. Anim Genet,2002,33(3):244~245
[32] Bodensteiner K J, Clay C M, Mueller C I, Sawyer H R. Molecular cloning of the ovine growth /difterentiation factor-9 gene and expression of growth/differentiation factor-9 in ovine and bovine ovaries[J]. Biol Reprod, 1999.60(2):381~3 86.
[33] McPhenon A C, Lee S J. GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamiIy containing a novel pattern of cvsteines [J]. IBTOIChem, l993,268(5): 3444~3449
[34] McGrath S A, Esduela A F. Lee S J.Oocyte specific expression of growth/differentiation factor 9[J]. Mol Endocr-inod, 1995,9(1):131~136.
[35] Jaatinen R, Laitinen M P, Vuojolainen K, Aaltonen J, houhio H, Heikinheimo K, Lehtonen E, Ritvos o. Localization of growth differentiation factor-9 (GDF9) mRNA and protein in rat ovaries and cDNA cloning of rat GDF9 and its novel homolog GDF9B[J]. Mol Cell Endocrinol, 1999,156(1-2):189~193.
[36] Fitzpatrick S L, Sindoni D M, Shughrue P .T, Lane M V. Merchenthaler 1 J, Frail D E.Expression of growrth differentiation factor-9 messenger ribonucleic acid in ovarian and nonovarian rodent and human tissues[J]. Endocrinology:1998, 139(5):2571~2578.
[37] Hayashi K. PCR-SSCP:A simple and sensitive method for detection of mutation in the genomic DNA[J]. PCR Methods Appl, 1991, 1:34～38.
[38] Vitt U A, Hsueh A J. Stage-dependent role of growth differentiation factor-9 in ovarian follicle development[J]. Mol Cell Endocrino1,2002,186(2):271~275
[39] Weiner H L, Cohen J A. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects[J]. Mult Scler, 2002,186(2):211~217
[40] Incerti B ,Dong J Borsani G , Matzuk M M , Strcture of the Mouse growth differentiation factor-9 gene[J].Biochem Biophys Acta, 1994,1222(1):125~128.
[41] 李碧侠,储明星,王金玉.绵羊 GDF9 基因 PCR-SSCP 分析[J].遗传学报,2003,30(4):307~310.
[42] Dong J W, Albertini D F, Nishimori K, KumarT R, Lu 议 Mat zuk M M. Growth differentiation factor9 is required during early ovarian folliculo[J].genesis Nature, 1996 383(6600): 531~535
[43] Juengel J L, Hudson N I, Heath D A, Smith P, Reader K L, Law rence S B O'Connell A R, Laitinen M P, Cranfield M, Groome N P, Ritvos O, MeNatty K P. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep[J].Biol Reprod, 2002 67(6): 1777~1789
[44] Davis G H,McEwan J C,Fennessy P F.Evidenee for the presence of a major gene influencing ovulation rate on the X chomosome of sheep(J}.Biol Reprod,1991,44(4): 620～624.
[45] Jennifer L.Dube,Pei Wang et al .The Bone Morphogenetic Protein 15 Gene Is X-Linked and ExPressed in Oocytes. [J].Mole Endor,1998,12(12):1809~1817
[46] Callowav. S.M,et a1.Mutations in an oocyte-derived growth differentiation facter gene (BMP15) cause increased ovulation rate and infertility in a dosage-senstive manner [J] Nature Genetics,2000,(25):279~283
[47] otsuka Fumio,Zuxu Yao,Lee Taek-hoo,Yamamoto Shin,Erickson Gregory F,and Shimasaki Shunichi.Bone morphogenetic Protein-15 inhibits follicle-stimulating hormone action by suppressing FSH recepter expression [J]. Bio Chem,2001,276(14):11387~11392
[48] Liao W X, Moore R K, Ostuka F, Shimasaki S. Functional and molecular Characterization ofnaturally occurring mutations in the oocyte-secr-etcd factors BMP-1 5 and GDF9[J]. Bio1 Chem, 2004.Feb, l 7[Epub ahead o
[49] otsuka Fumio,Zuxu Yao,Lee Taek-hoo,Yamamoto Shin,Erickson Gregory F,and Shimasaki Shunichi.Bone morphogenetic Protein-15 [J]. Bio Chem,2000,275(50):39523~3928
[50] Grant W.Montgomery,Susan M Galloway ,George H .Davis and Kwnneth P.McNatty, Genes Controlling Ovulation Rate in Sheep[J].Reprod , 2001; 121:848~852
[51] Galloway, S.M., McNatty, K.P., Cambridge, L.M., Laitinen, M.P.E., Juengel, J.L., Jokiranta, T.S., McLaren, R.J., Luiro, K., Dodds, K.G., Montgomery, G.W., Beattie, A.E., Davis, G.H., Ritvos, O., 2000. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nat. Genet. 25, 279~283.
[52] Lecerf, F., Mulsant, P., Elsen, J.M., Bodin, L., 2002. Localisation and mapping of a major gene controlling ovulation rate in Lacaune sheep. In: Proceedings of the Seventh World Congress on Genetics Applied to Livestock Production, Montpellier, France, CD-ROM Communication 08-31, 4pp
[53]桑林华.小尾寒羊高繁殖力侯选基因 BMPR-IA, BMP15 和 GDF9 的研究[M]. 学位论文.2005 扬州
[54] Davis, G.H., Bruce, G.D., Dodds, K.G., 2001a. Ovulation rate and litter size of prolific Inverdale (FecXI) and Hanna (FecXH) sheep. Proc. Assoc. Adv. Anim. Breed. Genet. 14, 175–178.
[55] Davis, G.H., Dodds, K.G., Bruce, G.D., 1999. Combined effect of the Inverdale and Booroola prolificacy genes on ovulation rate in sheep. Proc. Assoc. Adv. Anim. Breed. Genet. 13, 74–77.
[56] Davis, G.H., Dodds, K.G., Wheeler, R., Jay, N.P., 200IB. Evidence that an imprinted gene on the X chromosomeincreases ovulation rate in sheep. Biol. Reprod. 64, 216–221.
[57] Jonmundsson, J.V., Adalsteinsson S., 1985. Single genes for fecundity in Icelandic sheep. In: Land, R.B., Robinson,D.W. (Eds.), Genetics of Reproduction in Sheep. Butterworths, London, UK, pp. 159–168.
[58] Davis, G.H., Galloway, S.M., Ross, I.K., Gregan, S.M., Ward, J., Nimbkar, B.V., Ghalsasi, P.M., Nimbkar, C.,Gray, G.D., Inounu, I., Tiesnamurti, B., Martyniuk, E., Eythorsdottir, E., Mulsant, P., Lecerf, F., Hanrahan, J.P.,Bradford, G.E., Wilson, T., 2002. DNA tests in prolific sheep from eight countries provide new evidence onorigin of the Booroola (FecB) mutation. Biol. Reprod. 66, 1869–1874.
[59] Malher, X., Le Chere, A.K., 1998. High prolificacy in Belle-Ile sheep (Brittany, France): major effects of a putative single gene and the Awh colour gene on ovulation rate and litter size. Reprod. Nutr. Dev. 38, 473–484.
[60]Davis G.H. .Fecundity genes in sheep. Animal Reproduction Science, 82–83(2004), 247~253.[61] Lecerf F, Mulsant P, Elsen, et al. Localisation and mapping of a major gene controllingovulation rate in Lacaune sheep. In: Proceedings of the Seventh World Congress on Genetics Applied to Livestock Production [J], Montpellier, France, CD-ROM Communication. 2002, 0831, 4pp.
[61] 朱二勇 BMPR-IB基因作为新疆几种绵羊多胎性能候选基因的研究[M].学位论文 乌鲁木齐
[62] Ma 勺 niuk E, Radomsa M J. A single gene for prolificacy in Olkuska sheep. In: Elsen, J.M., Bodin, L., Thimonier,1. (Eds.), Major Genes for Reproduction in Sheep. INRA, Paris, France, 1991, pp. 8592.
[63] Davis G H, Galloway S M, Wilson T, et al. Major genes for prolificacy in NZ flocks[J]. Proc. Soc. Sheep Beef Cattle Vet. 2003, 33:3542.
[64] Sadighi M, Bodensteiner K J, Beattie A E, et al,.Genetic mapping of ovine growth differentiation factor 9 (GDF9) to sheep chromosome 5. Anim Genet, 2002, 33(3):244-245
[65] 管峰,艾君涛,杨利国.一种 SNP 检测新方法:四引物扩增受阻突变体系 PCR 技术.生命的化学.2004,24 (6):514~516.
[65] 王根林,毛鑫智,赵宗盛,等.分析发现我国湖羊和小尾寒羊存在(FecB)多胎基因.南京农业大学学报,2003,26(1):104~106
[66] 张志峰, 史洪才,武坚,等.微卫星 DNA 聚丙烯酰胺凝胶电泳(PAGE)银染法的改良. 生物技术.2005,3:51~53.
[67] 史洪才, 武坚, 朱二勇. 等 BMPR~IB 基因作为新疆多浪羊多胎性能候选基因的研究. 中国草食动物.2006,2:12~14
[68] 柳淑芳,姜运良,杜立新.BMPR-IB 和 BMP15 基因作为小尾寒羊多胎性能候选基因的研究. 遗传学报,2003, 30(8):755～760.
[69] 储明星,桑林华,王金玉,方丽,叶素成.小尾寒羊高繁殖力候选基因 BMP 15 和 GDF 9 的研究. 遗传学报,2005, 32 ( 1) : 38～45.
[2] Fortune JE,et al.〔J〕.Biol0gy of reproduction,1994,50:225～232
[3] Diaz T et al. Human chorionic gonadotropin induced alterations inovarian follicular dynamics during the estrus cycle of heifers[J].J.Anim.Sci.1998,76: 1929～1936
[4] 雪雪芹. 牛、羊多胎性状的 DNA 分子标记研究[D].学位论文.2002.陕西
[5] Hould, A. et a1.(1994) Structure of the bovine follicle- stimulating hormone receptor complementary DNA and expression in bovine tissues. Mol. Reprod. Dev. 39:127-135.
[6] Heckert, L.L., Daley, LJ. and Griswold, M. (1992) Structure rganization of the follicle-stimulating hormone receptor gene Mo1.CelLEndocrino1.1992, 6:70-80.
[7] Snyder , D.A (1986) Superovulation of cows and heifers selected for twinning. Theriogenology.25:200.
[8] indon, B.M.et al. (1986)Genetic and hormonal factors affecting Superovulation . Theriogenology. 25(1): 53-70
[9] 毕晓丹 小尾寒羊高繁殖力候选基因 ESR 的研究(M),学位论文 2005,吉林 延吉
[10] 吴常信,张伯洪.动物遗传育种学总论(主编:张沅).北京:北京农业大学出版社,1996.225
[11] COGNOSAG/Standard ised Genetic Bomenclature for Sheep and Goat.Lavoisier, Paris,1989
[12] McNatty K P, Hudson N, Henderson K M, et al. Differences in gonadotrophin concentrations and pituitary responsiveness to GnRH between Booroola ewes which were homozygous (FF) , heterozygous (F+) and non~carriers (++) of a major gene influencing their ovulation rate. J.Repro.Fert..,1987,80:577~588.
[13] Mcnatty, K.P., Hudson, N.L., Shaw, L., et al. Plasma concentrations of FSH, LH, thyroid~stimulating hormone and growth hormone after exogenous stimulation with GnRH, TRH and GHRH in Booroola ewes that are homozygous carriers or non~ carriers of the Fec(B) gene. Journal of Reproduction and Fertility .1994,102: 177~183.
[14] McNatty,K.P.etal.In:Major Gene for Reproductionin Sheep . Eds, J-Melsen , L.Bodin&J . Thimonier. Institute National edela Recherche,Agronomique, Paris.199IB.105~ 124.
[15] Cummins, L.J.etal[J]. Repro.Ferti,1983,67:1~7
[16] Mulsant P,Lecerf F,Fabre S,Setal. Mutation in Bone morphogenetic protein receptor~IB is associated with increased ovulation rate in Booroola Merino ewes. proceedings of the National Academy of Sciences of the USA,2001,98: 5104~ 5109.
[17] Wilson T,Wu X Y, Juenge I J etal.Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of Bone morphogenetic protein IB receptor(ALK~6) that is expressed in Both oocytes and granulosa cells. Biology of Reproduction. 2001, 64:1225~ 1235.
[18]Mulsant P,Lecerf F,Fabre S, et al. Mutation in Bone morphogenetic protein receptor~IB is associatedwith increased ovulation rate in Booroola Merino ewes. proceedings of the National Academy of Sciences of the USA,2001,98: 5104~ 5109.
[19] Souza C J, Campbell BK, McNeilly A S, et al. The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPRIB). J Endocrinol. 2001,169(2):Rl~R6.
[20] Liu F, Ventura F, Doody J, et al. Human type II receptor for bone morphogenic proteins (BMPs): extension of the two~kinase receptor model to the BMPs. Mol Cell Biol ,1995, 15(7):3479~3486.
[21] Attisano L,Wrana J L,Montalvo E,et al.Activation of signal in by the activin receptor complex.Mol Cell Biol, 1996, 16:1066~1073.
[22] Fujii M, Takeda K, Imamura T, Aoki H, Sampath T K, Enomoto S, Kawabata M, Kato M, Ichijo H, Miyazono K. Roles of bone morphogenetic protein type Ireceptors and Smad proteins in osteoblast and chondroblast differentiation[J]. Mol BiolCell ,1999, 10(11): 3801~3813.
[23] Mishina Y, Suzuki A, Gilbert D J, Copeland N G, Jenkins N A, Ueno N, Behringer R R. Genomic organization and chromosomal location of the mouse type I BMP-2/4 receptor[J]. Biochem Biophys Res Commun, 1995, 206(1):310~317
[24] Hayashi K. PCR-SSCP:A simple and sensitive method for detection of mutation in the genomic DNA[J]. PCR Methods Appl, 1991, 1:34～38.
[25] Larsen,N J, Nielsen V H. Apa I and Cfo I polymorphisms in the porcine growth hormone gene[J]. Animal Genetics, 1993, 24(1):71~76
[26] 闫亚东,曾勇庆,储明星. 小尾寒羊 BMPR-IB 基因单核苷酸多态性及其与产羔性能关系的研究[M].学位论文 2004.山东
[27] 钟发刚等,绵羊多胎性状分子标记辅助选择技术研究[M].学位论文.2004 石河子
[28] 刘淑芳 小尾寒羊多胎性状相关基因的鉴定与研究[D].学位论文.2004.山东
[29] 贾存灵 小尾寒羊多胎性状主要侯选基因及繁殖相关基因表达量研究[D].学位论文 2005 北京
[30] Hanrahan P ,l, Gregan S M, Mulsant P, Mullen M, Davis G H, Powcll R.Galloway S M. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belelare sheep (Ovis aries) [J]. Bio1 Reprod, 2004.70(4):900~909.
[31] Sadighi M, Bodensteiuer K J, Beattie A E, Galloway S M. Genetic mapping of ovine growth differentiation factor 9 (GDF9) to sheep chromosome 5[J]. Anim Genet,2002,33(3):244~245
[32] Bodensteiner K J, Clay C M, Mueller C I, Sawyer H R. Molecular cloning of the ovine growth /difterentiation factor-9 gene and expression of growth/differentiation factor-9 in ovine and bovine ovaries[J]. Biol Reprod, 1999.60(2):381~3 86.
[33] McPhenon A C, Lee S J. GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamiIy containing a novel pattern of cvsteines [J]. IBTOIChem, l993,268(5): 3444~3449
[34] McGrath S A, Esduela A F. Lee S J.Oocyte specific expression of growth/differentiation factor 9[J]. Mol Endocr-inod, 1995,9(1):131~136.
[35] Jaatinen R, Laitinen M P, Vuojolainen K, Aaltonen J, houhio H, Heikinheimo K, Lehtonen E, Ritvos o. Localization of growth differentiation factor-9 (GDF9) mRNA and protein in rat ovaries and cDNA cloning of rat GDF9 and its novel homolog GDF9B[J]. Mol Cell Endocrinol, 1999,156(1-2):189~193.
[36] Fitzpatrick S L, Sindoni D M, Shughrue P .T, Lane M V. Merchenthaler 1 J, Frail D E.Expression of growrth differentiation factor-9 messenger ribonucleic acid in ovarian and nonovarian rodent and human tissues[J]. Endocrinology:1998, 139(5):2571~2578.
[37] Hayashi K. PCR-SSCP:A simple and sensitive method for detection of mutation in the genomic DNA[J]. PCR Methods Appl, 1991, 1:34～38.
[38] Vitt U A, Hsueh A J. Stage-dependent role of growth differentiation factor-9 in ovarian follicle development[J]. Mol Cell Endocrino1,2002,186(2):271~275
[39] Weiner H L, Cohen J A. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects[J]. Mult Scler, 2002,186(2):211~217
[40] Incerti B ,Dong J Borsani G , Matzuk M M , Strcture of the Mouse growth differentiation factor-9 gene[J].Biochem Biophys Acta, 1994,1222(1):125~128.
[41] 李碧侠,储明星,王金玉.绵羊 GDF9 基因 PCR-SSCP 分析[J].遗传学报,2003,30(4):307~310.
[42] Dong J W, Albertini D F, Nishimori K, KumarT R, Lu 议 Mat zuk M M. Growth differentiation factor9 is required during early ovarian folliculo[J].genesis Nature, 1996 383(6600): 531~535
[43] Juengel J L, Hudson N I, Heath D A, Smith P, Reader K L, Law rence S B O'Connell A R, Laitinen M P, Cranfield M, Groome N P, Ritvos O, MeNatty K P. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep[J].Biol Reprod, 2002 67(6): 1777~1789
[44] Davis G H,McEwan J C,Fennessy P F.Evidenee for the presence of a major gene influencing ovulation rate on the X chomosome of sheep(J}.Biol Reprod,1991,44(4): 620～624.
[45] Jennifer L.Dube,Pei Wang et al .The Bone Morphogenetic Protein 15 Gene Is X-Linked and ExPressed in Oocytes. [J].Mole Endor,1998,12(12):1809~1817
[46] Callowav. S.M,et a1.Mutations in an oocyte-derived growth differentiation facter gene (BMP15) cause increased ovulation rate and infertility in a dosage-senstive manner [J] Nature Genetics,2000,(25):279~283
[47] otsuka Fumio,Zuxu Yao,Lee Taek-hoo,Yamamoto Shin,Erickson Gregory F,and Shimasaki Shunichi.Bone morphogenetic Protein-15 inhibits follicle-stimulating hormone action by suppressing FSH recepter expression [J]. Bio Chem,2001,276(14):11387~11392
[48] Liao W X, Moore R K, Ostuka F, Shimasaki S. Functional and molecular Characterization ofnaturally occurring mutations in the oocyte-secr-etcd factors BMP-1 5 and GDF9[J]. Bio1 Chem, 2004.Feb, l 7[Epub ahead o
[49] otsuka Fumio,Zuxu Yao,Lee Taek-hoo,Yamamoto Shin,Erickson Gregory F,and Shimasaki Shunichi.Bone morphogenetic Protein-15 [J]. Bio Chem,2000,275(50):39523~3928
[50] Grant W.Montgomery,Susan M Galloway ,George H .Davis and Kwnneth P.McNatty, Genes Controlling Ovulation Rate in Sheep[J].Reprod , 2001; 121:848~852
[51] Galloway, S.M., McNatty, K.P., Cambridge, L.M., Laitinen, M.P.E., Juengel, J.L., Jokiranta, T.S., McLaren, R.J., Luiro, K., Dodds, K.G., Montgomery, G.W., Beattie, A.E., Davis, G.H., Ritvos, O., 2000. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J]. Nat. Genet. 25, 279~283.
[52] Lecerf, F., Mulsant, P., Elsen, J.M., Bodin, L., 2002. Localisation and mapping of a major gene controlling ovulation rate in Lacaune sheep. In: Proceedings of the Seventh World Congress on Genetics Applied to Livestock Production, Montpellier, France, CD-ROM Communication 08-31, 4pp
[53]桑林华.小尾寒羊高繁殖力侯选基因 BMPR-IA, BMP15 和 GDF9 的研究[M]. 学位论文.2005 扬州
[54] Davis, G.H., Bruce, G.D., Dodds, K.G., 2001a. Ovulation rate and litter size of prolific Inverdale (FecXI) and Hanna (FecXH) sheep. Proc. Assoc. Adv. Anim. Breed. Genet. 14, 175–178.
[55] Davis, G.H., Dodds, K.G., Bruce, G.D., 1999. Combined effect of the Inverdale and Booroola prolificacy genes on ovulation rate in sheep. Proc. Assoc. Adv. Anim. Breed. Genet. 13, 74–77.
[56] Davis, G.H., Dodds, K.G., Wheeler, R., Jay, N.P., 200IB. Evidence that an imprinted gene on the X chromosomeincreases ovulation rate in sheep. Biol. Reprod. 64, 216–221.
[57] Jonmundsson, J.V., Adalsteinsson S., 1985. Single genes for fecundity in Icelandic sheep. In: Land, R.B., Robinson,D.W. (Eds.), Genetics of Reproduction in Sheep. Butterworths, London, UK, pp. 159–168.
[58] Davis, G.H., Galloway, S.M., Ross, I.K., Gregan, S.M., Ward, J., Nimbkar, B.V., Ghalsasi, P.M., Nimbkar, C.,Gray, G.D., Inounu, I., Tiesnamurti, B., Martyniuk, E., Eythorsdottir, E., Mulsant, P., Lecerf, F., Hanrahan, J.P.,Bradford, G.E., Wilson, T., 2002. DNA tests in prolific sheep from eight countries provide new evidence onorigin of the Booroola (FecB) mutation. Biol. Reprod. 66, 1869–1874.
[59] Malher, X., Le Chere, A.K., 1998. High prolificacy in Belle-Ile sheep (Brittany, France): major effects of a putative single gene and the Awh colour gene on ovulation rate and litter size. Reprod. Nutr. Dev. 38, 473–484.
[60]Davis G.H. .Fecundity genes in sheep. Animal Reproduction Science, 82–83(2004), 247~253.[61] Lecerf F, Mulsant P, Elsen, et al. Localisation and mapping of a major gene controllingovulation rate in Lacaune sheep. In: Proceedings of the Seventh World Congress on Genetics Applied to Livestock Production [J], Montpellier, France, CD-ROM Communication. 2002, 0831, 4pp.
[61] 朱二勇 BMPR-IB基因作为新疆几种绵羊多胎性能候选基因的研究[M].学位论文 乌鲁木齐
[62] Ma 勺 niuk E, Radomsa M J. A single gene for prolificacy in Olkuska sheep. In: Elsen, J.M., Bodin, L., Thimonier,1. (Eds.), Major Genes for Reproduction in Sheep. INRA, Paris, France, 1991, pp. 8592.
[63] Davis G H, Galloway S M, Wilson T, et al. Major genes for prolificacy in NZ flocks[J]. Proc. Soc. Sheep Beef Cattle Vet. 2003, 33:3542.
[64] Sadighi M, Bodensteiner K J, Beattie A E, et al,.Genetic mapping of ovine growth differentiation factor 9 (GDF9) to sheep chromosome 5. Anim Genet, 2002, 33(3):244-245
[65] 管峰,艾君涛,杨利国.一种 SNP 检测新方法:四引物扩增受阻突变体系 PCR 技术.生命的化学.2004,24 (6):514~516.
[65] 王根林,毛鑫智,赵宗盛,等.分析发现我国湖羊和小尾寒羊存在(FecB)多胎基因.南京农业大学学报,2003,26(1):104~106
[66] 张志峰, 史洪才,武坚,等.微卫星 DNA 聚丙烯酰胺凝胶电泳(PAGE)银染法的改良. 生物技术.2005,3:51~53.
[67] 史洪才, 武坚, 朱二勇. 等 BMPR~IB 基因作为新疆多浪羊多胎性能候选基因的研究. 中国草食动物.2006,2:12~14
[68] 柳淑芳,姜运良,杜立新.BMPR-IB 和 BMP15 基因作为小尾寒羊多胎性能候选基因的研究. 遗传学报,2003, 30(8):755～760.
[69] 储明星,桑林华,王金玉,方丽,叶素成.小尾寒羊高繁殖力候选基因 BMP 15 和 GDF 9 的研究. 遗传学报,2005, 32 ( 1) : 38～45.