绵羊Tacr3基因多态性与产羔数的关联分析
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摘要
本研究旨在探究绵羊速激肽受体3(tachykinin receptor 3,Tacr3)基因g.21484478A>C、g.21560640C>T和g.21560688T>C位点多态性与绵羊产羔数之间的关系,为绵羊高繁殖力分子育种提供新的遗传标记。利用全基因组重测序结合Sequenom MassARRAY?SNP技术对常年发情绵羊品种(小尾寒羊、湖羊和策勒黑羊)和季节性发情绵羊品种(滩羊、苏尼特羊和草原型藏羊)Tacr3基因3个多态位点进行检测,并与小尾寒羊产羔数进行关联分析。结果表明,3个位点均存在3种基因型,其中g.21484478A>C位点存在AA、CC和CA基因型,g.21560640C>T位点存在TT、CC和TC基因型,g.21560688T>C位点存在TT、CC和CT基因型,3个多态位点基因型频率和等位基因频率在两种发情模式绵羊品种间均达到差异极显著水平(P<0.01)。群体遗传学分析表明,g.21484478A>C位点在滩羊和策勒黑羊中均表现为中度多态(0.25T位点在6个绵羊品种中均表现为中度多态;g.21560688T>C位点在小尾寒羊、苏尼特羊、湖羊和草原型藏羊中均表现为低度多态。卡方适合性检验表明,g.21560640C>T位点在6个绵羊品种中均处于哈代-温伯格平衡状态(P>0.05);g.21484478A>C位点在草原型藏羊中处于哈代-温伯格不平衡状态(P<0.05);g.21560688T>C位点在滩羊、策勒黑羊中处于哈代-温伯格不平衡状态(P<0.05)。关联分析表明,3个多态位点与小尾寒羊第一、二、三胎产羔数均无显著关联(P>0.05)。推测Tacr3基因3个多态位点均不适用于小尾寒羊产羔数选育。
The aim of this study was to elucidate the association between tachykinin receptor 3(Tacr3) gene polymorphism(g.21484478 A>C,g.21560640 C>T and g.21560688 T>C loci) and litter size in sheep,providing new genetic markers for high prolific molecular breeding of sheep.Year-round estrous sheep breeds(Small-tail Han sheep,Hu sheep and Cele Black sheep) and seasonal estrous sheep breeds(Tan sheep,Sunite sheep and Prairie Tibetan sheep) were selected and Sequenom MassARRAY?SNP assay was applied to detect the genotypes of g.21484478 A>C,g.21560640 C>T and g.21560688 T>C loci of Tacr3 gene,then the association was analyzed between Tacr3 gene polymorphism and litter size in Small-tail Han sheep.The results showed that three genotypes were found at g.21484478 A>C(AA,CA and CC),g.21560640 C>T(TT,TC and CC) and at g.21560688 T>C(TT,CT and CC) loci in both year-round estrous and seasonal estrous sheep,both genotype frequency and gene frequency of three loci of Tacr3 gene were extremely significantly different between year-round estrous and seasonal estrous sheep(P<0.01).Population genetic analysis showed that the g.21484478 A>C locus was at moderate polymorphism(0.25T locus was at moderate polymorphism in 6 sheep breeds;The g.21560688 T>C locus was at low polymorphism in Small-tail Han sheep,Sunite sheep,Hu sheep and Prairie Tibetan sheep.The χ~2 test indicated that the g.21560640 C>T locus of 6 sheep breeds was in Hardy-Weinberg equilibrium(P>0.05);The g.21484478 A>C locus of Prairie Tibetan sheep was not in Hardy-Weinberg equilibrium(P<0.05);The g.21560688 T>C locus of Tan sheep and Cele Black sheep was not in Hardy-Weinberg equilibrium(P<0.05).The association analysis indicated that the polymorphism of g.21484478 A>C,g.21560640 C>T and g.21560688 T>C had no correlation with the litter size of the first,second or third parity in Small-tail Han sheep(P>0.05).In conclusion,the three polymorphic loci of Tacr3 gene might not be suitable for breeding of Small-tailed Han sheep.
The aim of this study was to elucidate the association between tachykinin receptor 3(Tacr3) gene polymorphism(g.21484478 A>C,g.21560640 C>T and g.21560688 T>C loci) and litter size in sheep,providing new genetic markers for high prolific molecular breeding of sheep.Year-round estrous sheep breeds(Small-tail Han sheep,Hu sheep and Cele Black sheep) and seasonal estrous sheep breeds(Tan sheep,Sunite sheep and Prairie Tibetan sheep) were selected and Sequenom MassARRAY?SNP assay was applied to detect the genotypes of g.21484478 A>C,g.21560640 C>T and g.21560688 T>C loci of Tacr3 gene,then the association was analyzed between Tacr3 gene polymorphism and litter size in Small-tail Han sheep.The results showed that three genotypes were found at g.21484478 A>C(AA,CA and CC),g.21560640 C>T(TT,TC and CC) and at g.21560688 T>C(TT,CT and CC) loci in both year-round estrous and seasonal estrous sheep,both genotype frequency and gene frequency of three loci of Tacr3 gene were extremely significantly different between year-round estrous and seasonal estrous sheep(P<0.01).Population genetic analysis showed that the g.21484478 A>C locus was at moderate polymorphism(0.25
引文
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[7] KANAYA M,IWATA K,OZAWA H.Distinct dynorphin expression patterns with low- and high-dose estrogen treatment in the arcuate nucleus of female rats[J].Biology of Reproduction,2017,97(5):709-718.
[8] CORANDER M P,CHALLIS B G,THOMPSON E L,et al.The effects of neurokinin B upon gonadotropin release in male rodents[J].Journal of Neuroendocrinology,2010,22(3):181-187.
[9] TOPALOGLU A K,REIMANN F,GUCLU M,et al.Tac3 and Tacr3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction[J].Nature Genetics,2009,41(3):354-358.
[10] XIN X,ZHANG J,CHANG Y,et al.Association study of Tac3 and Tacr3 gene polymorphisms with idiopathic precocious puberty in Chinese girls[J].Journal of Pediatric Endocrinology & Metabolism,2015,28(1-2):65-71.
[11] 王婷.Tac3/Tacr3在黑线仓鼠繁殖过程中的调控作用[D].曲阜:曲阜师范大学,2016.WANG T.The mechanism of Tac3/Tacr3 participate in reproductive regulation of Cricetulus barabensis[D].Qufu:Qufu Normal University,2016.(in Chinese)
[12] NOEL S D,ABREU A P,XU S,et al.Tacr3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients[J].FASEB Journal,2014,28(4):1924-1937.
[13] 周梅,曹晓涵,贺小云,等.绵羊FGF7基因组织表达及其多态性与产羔数之间的关系[J].畜牧兽医学报,2018,49(3):525-533.ZHOU M,CAO X H,HE X Y,et al.Tissue expression and polymorphism of sheep FGF7 gene and their association with litter size[J].Chinese Journal of Animal and Veterinary Sciences,2018,49(3):525-533.(in Chinese)
[14] BUELL G,SCHULZ M F,ARKINSTALL S J,et al.Molecular characterisation,expression and localisation of human neurokinin-3 receptor[J].FEBS Letters,1992,299(1):90-95.
[15] 潘章源,狄冉,刘秋月,等.绵羊多羔主效基因BMPR1B的研究进展[J].家畜生态学报,2015,36(5):1-6.PAN Z Y,DI R,LIU Q Y,et al.Advances in ovine prolificacy gene BMPR1B[J].Journal of Domestic Animal Ecology,2015,36(5):1-6.(in Chinese)
[16] 张意茗.特发性低促性腺激素性性腺功能减退症致病基因筛选及IVF妊娠结局分析[D].济南:山东大学,2015.ZHANG Y M.Screening of causative genes in Chinese patients with idiopathic hypogonadotropic hypogonadism(IHH) and the reproductive performance of women with IHH during in vitro fertilization and embryo transfer treatment[D].Jinan:Shandong University,2015.(in Chinese)
[17] OBATA K,SHIMO T,OKUI T,et al.Tachykinin receptor 3 distribution in human oral squamous cell carcinoma[J].Anticancer Research,2016,36(12):6335-6341.
[18] NAVARRO V M,CASTELLANO J M,MCCONKEY S M,et al.Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat[J].American Journal of Physiology-endocrinology and Metabolism,2011,300(1):E202-E210.
[19] VALERO M S,FAQUNDES D S,GRASA L,et al.Contractile effect of tachykinins on rabbit small intestine[J].Acta Pharmacologica Sinica,2011,32(4):487-494.
[20] BARROS M,DEMPSTER E L,ILLOTT N,et al.Decreased methylation of the NK3 receptor coding gene (Tacr3) after cocaine-induced place preference in marmoset monkeys[J].Addiction Biology,2013,18(3):452-454.
[21] MOURA G R,PINHEIRO M,FREITAS A,et al.Species-specific codon context rules unveil non-neutrality effects of synonymous mutations[J].PLoS One,2011,6(10):e26817.
[22] 梁伟.癌症相关的同义突变对基因翻译过程的影响[D].南京:东南大学,2012.LIANG W.Silent mutations in cancer genomes have effects on translation efficiency[D].Nanjing:Southeast University,2012.(in Chinese)
[23] RUDOLPH K L M,SCHMITT B M,VILLAR D,et al.Codon-driven translational efficiency is stable across diverse mammalian cell states[J].PLoS Genetics,2016,12(5):e1006024.
[24] MYNAMPATI B K,MUTHUKUMARAPPA T,GHOSH S,et al.A silent mutation in human alpha-A crystallin gene in patients with age-related nuclear or cortical cataract[J].Bosnian Journal of Basic Medical Sciences,2017,17(2):114-119.
[2] 吕晓阳,孙伟,张想想,等.利用9个微卫星标记分析海门山羊和徐淮山羊的遗传多样性[J].中国畜牧杂志,2016,52(15):5-11.LYU X Y,SUN W,ZHANG X X,et al.Analyzing genetic diversity of Haimen goat,Xuhuai goat based on 9 microsatellite makers[J].Chinese Journal of Animal Science,2016,52(15):5-11.(in Chinese)
[3] VRIES F D,HAMANN H,DR?GEMüLLER C,et al.Analysis of associations between the prion protein genotype and reproduction traits in meat sheep breeds[J].Animal Science,2016,79(3):397-404.
[4] VáZQUEZARMIJO J F,ROJO R,LóPEZ D,et al.Trace elements in sheep and goats reproduction:A review[J].Tropical & Subtropical Agroecosystems,2016,14(1):1-13.
[5] JAKIMIUK A,PODLASZ P,CHMIELEWSKA-KRZESINSKA M,et al.Characterisation,localisation and expression of porcine Tacr1,Tacr2 and Tacr3 genes[J].Veterinární Medicína,2017,62(8):443-455.
[6] BILLINGS H J,CONNORS J M,ALTMAN S N,et al.Neurokinin B acts via the neurokinin-3 receptor in the retrochiasmatic area to stimulate luteinizing hormone secretion in sheep[J].Endocrinology,2010,151(8):3836-3846.
[7] KANAYA M,IWATA K,OZAWA H.Distinct dynorphin expression patterns with low- and high-dose estrogen treatment in the arcuate nucleus of female rats[J].Biology of Reproduction,2017,97(5):709-718.
[8] CORANDER M P,CHALLIS B G,THOMPSON E L,et al.The effects of neurokinin B upon gonadotropin release in male rodents[J].Journal of Neuroendocrinology,2010,22(3):181-187.
[9] TOPALOGLU A K,REIMANN F,GUCLU M,et al.Tac3 and Tacr3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction[J].Nature Genetics,2009,41(3):354-358.
[10] XIN X,ZHANG J,CHANG Y,et al.Association study of Tac3 and Tacr3 gene polymorphisms with idiopathic precocious puberty in Chinese girls[J].Journal of Pediatric Endocrinology & Metabolism,2015,28(1-2):65-71.
[11] 王婷.Tac3/Tacr3在黑线仓鼠繁殖过程中的调控作用[D].曲阜:曲阜师范大学,2016.WANG T.The mechanism of Tac3/Tacr3 participate in reproductive regulation of Cricetulus barabensis[D].Qufu:Qufu Normal University,2016.(in Chinese)
[12] NOEL S D,ABREU A P,XU S,et al.Tacr3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients[J].FASEB Journal,2014,28(4):1924-1937.
[13] 周梅,曹晓涵,贺小云,等.绵羊FGF7基因组织表达及其多态性与产羔数之间的关系[J].畜牧兽医学报,2018,49(3):525-533.ZHOU M,CAO X H,HE X Y,et al.Tissue expression and polymorphism of sheep FGF7 gene and their association with litter size[J].Chinese Journal of Animal and Veterinary Sciences,2018,49(3):525-533.(in Chinese)
[14] BUELL G,SCHULZ M F,ARKINSTALL S J,et al.Molecular characterisation,expression and localisation of human neurokinin-3 receptor[J].FEBS Letters,1992,299(1):90-95.
[15] 潘章源,狄冉,刘秋月,等.绵羊多羔主效基因BMPR1B的研究进展[J].家畜生态学报,2015,36(5):1-6.PAN Z Y,DI R,LIU Q Y,et al.Advances in ovine prolificacy gene BMPR1B[J].Journal of Domestic Animal Ecology,2015,36(5):1-6.(in Chinese)
[16] 张意茗.特发性低促性腺激素性性腺功能减退症致病基因筛选及IVF妊娠结局分析[D].济南:山东大学,2015.ZHANG Y M.Screening of causative genes in Chinese patients with idiopathic hypogonadotropic hypogonadism(IHH) and the reproductive performance of women with IHH during in vitro fertilization and embryo transfer treatment[D].Jinan:Shandong University,2015.(in Chinese)
[17] OBATA K,SHIMO T,OKUI T,et al.Tachykinin receptor 3 distribution in human oral squamous cell carcinoma[J].Anticancer Research,2016,36(12):6335-6341.
[18] NAVARRO V M,CASTELLANO J M,MCCONKEY S M,et al.Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat[J].American Journal of Physiology-endocrinology and Metabolism,2011,300(1):E202-E210.
[19] VALERO M S,FAQUNDES D S,GRASA L,et al.Contractile effect of tachykinins on rabbit small intestine[J].Acta Pharmacologica Sinica,2011,32(4):487-494.
[20] BARROS M,DEMPSTER E L,ILLOTT N,et al.Decreased methylation of the NK3 receptor coding gene (Tacr3) after cocaine-induced place preference in marmoset monkeys[J].Addiction Biology,2013,18(3):452-454.
[21] MOURA G R,PINHEIRO M,FREITAS A,et al.Species-specific codon context rules unveil non-neutrality effects of synonymous mutations[J].PLoS One,2011,6(10):e26817.
[22] 梁伟.癌症相关的同义突变对基因翻译过程的影响[D].南京:东南大学,2012.LIANG W.Silent mutations in cancer genomes have effects on translation efficiency[D].Nanjing:Southeast University,2012.(in Chinese)
[23] RUDOLPH K L M,SCHMITT B M,VILLAR D,et al.Codon-driven translational efficiency is stable across diverse mammalian cell states[J].PLoS Genetics,2016,12(5):e1006024.
[24] MYNAMPATI B K,MUTHUKUMARAPPA T,GHOSH S,et al.A silent mutation in human alpha-A crystallin gene in patients with age-related nuclear or cortical cataract[J].Bosnian Journal of Basic Medical Sciences,2017,17(2):114-119.