Exploring the Novel Genetic Variant of PITX1 Gene and Its Effect on Milk Performance in Dairy Goats
LAN Xian-yong, ZHAO Hai-yu, LI Zhuan-jian, ZHOU Rui, PAN Chuan-ying, LEI Chu-zhao, CHEN Hong
1.College of Animal Science and Technology, Northwest A&F University/Shaanxi Key Laboratory of Molecular Biology for Agriculture,Yangling 712100, P.R.China
2.College of Life Sciences, Northwest A&F University, Yangling 712100, P.R.China
摘要 Paired-like homeodomain transcription factor 1 (PITX1) plays an important role in pituitary development by indirectly regulating the expression of the GH and PRL genes, and therefore PITX1 gene is regarded as a potential candidate gene for building the relationship between the gene polymorphism and milk traits. The aim of this study was to explore the novel genetic variant in PITX1 gene and its effect on milk performance in dairy goats. Herein, a novel genetic variation (NW_00314033: g.201G>A or IVS1+41G>A) located at nt41 position of the first intron of the goat PITX1 gene was reported at the P1 locus, which can be genotyped by the Msp I PCR-RFLP. In the Msp I PCR-RFLP analyis, the GG variant was a major genotype, and the A variant was a minor allele in Guanzhong dairy goats which was at Hardy-Weinberg disequilibrium (chi-square c2=140, P<0.01). The establishment of associations between different genotypes and milk performance was performed in the analyzed population. A total of three significant associations of the polymorphism with average milk fat content (%) (P=0.045), morning milk fat content (%) (P=0.049), and afternoon milk fat content (%) (P=0.050), were found, respectively. A significant relationship between the polymorphism and average total solid content (P=0.029) was also detected. This novel single nucleotide polymorphism (SNP) extended the spectrum of genetic variation of the goat PITX1 gene, and its significant association with milk performance would benefit from the application of DNA markers related to improving milk performance through marker-assisted selection (MAS) in dairy goats.
Abstract Paired-like homeodomain transcription factor 1 (PITX1) plays an important role in pituitary development by indirectly regulating the expression of the GH and PRL genes, and therefore PITX1 gene is regarded as a potential candidate gene for building the relationship between the gene polymorphism and milk traits. The aim of this study was to explore the novel genetic variant in PITX1 gene and its effect on milk performance in dairy goats. Herein, a novel genetic variation (NW_00314033: g.201G>A or IVS1+41G>A) located at nt41 position of the first intron of the goat PITX1 gene was reported at the P1 locus, which can be genotyped by the Msp I PCR-RFLP. In the Msp I PCR-RFLP analyis, the GG variant was a major genotype, and the A variant was a minor allele in Guanzhong dairy goats which was at Hardy-Weinberg disequilibrium (chi-square c2=140, P<0.01). The establishment of associations between different genotypes and milk performance was performed in the analyzed population. A total of three significant associations of the polymorphism with average milk fat content (%) (P=0.045), morning milk fat content (%) (P=0.049), and afternoon milk fat content (%) (P=0.050), were found, respectively. A significant relationship between the polymorphism and average total solid content (P=0.029) was also detected. This novel single nucleotide polymorphism (SNP) extended the spectrum of genetic variation of the goat PITX1 gene, and its significant association with milk performance would benefit from the application of DNA markers related to improving milk performance through marker-assisted selection (MAS) in dairy goats.
This paper was funded by the National Natural Science Foundation of China (31172184), the Young New Star Project on Science & Technology of Shaanxi Province, China (2011kjxx64), the Natural Science Foundation of Shaanxi Province of China (2011JQ3009), the Young Topnotch Researcher Support Project of Northwest A&F University, China (QNGG-2009-007), and the Special Fund for Basic Scientific Research and Operation Expenses in Sci-Tech Innovation of Northwest A&F University, China (QN2011102).
LAN Xian-yong, ZHAO Hai-yu, LI Zhuan-jian, ZHOU Rui, PAN Chuan-ying, LEI Chu-zhao, CHEN Hong.
2013.
Exploring the Novel Genetic Variant of PITX1 Gene and Its Effect on Milk Performance in Dairy Goats. Journal of Integrative Agriculture, 12(1): 118-126.
[1]Angiolillo A, Amills M, Urrutia B, Doménech A, Sastre Y,Badaoui B, Jordana J. 2007. Identification of a singlenucleotide polymorphism at intron 16 of the caprineacyl-coenzyme A: diacylglycerol acyltransferase 1(DGAT1) gene. Journal of Dairy Research, 74, 47-51
[2]Bach I, Carrière C, Ostendorff H P, Andersen B, RosenfeldM G. 1997. Afamily of LIMdomain-associated cofactorsconfer transcriptional synergism between LIM and Otxhomeodomain proteins. Genes and Development, 11,1370-1380
[3]Balogh O, Kovács K, Kulcsár M, Gáspárdy A, Zsolnai A,Kátai L, Pécsi A, Fésüs L, Butler WR, Huszenicza G.2009. AluI polymorphism of the bovine growth hormone(GH) gene, resumption of ovarian cyclicity, milkproduction and loss of body condition at the onset oflactation in dairy cows. Theriogenology, 71, 553-559
[4]Broke A, Matika O, Wilson A D, Anderson J, Morin A C,Finlayson H A, Reiner G, Willems H, Bishop S C,Archibald A L, et al. 2011. An intronic polymorphism inthe porcine IRF7 gene is associated with better healthand immunity of the host during Sarcocystis infection,and affects interferon signalling. Animal Genetics, 42,386-394
[5]Carvalho L, Ward R D, Brinkmeier M L, Anne P M, VesperA H, Camper S A. 2006. Molecular basis for pituitarydysfunction: comparison of Prop1 and Pit1 mutant mice.Developmental Biology, 295, 340.
[6]Castinetti F, Brinkmeier M L, Gordon D F, Vella K R, Kerr JM, Mortensen A H, Hollenberg A, Brue T, Ridgway EC, Camper S A. 2011. PITX2 and PITX1 regulatethyrotroph function and response to hypothyroidism.Molecular Endocrinology, 25, 1950-1960
[7]Cruz J B, Nunes V S, Clara SA, Perone D, Kopp P, NogueiraC R. 2010. Molecular analysis of the PROP1 and HESX1genes in patients with septo-optic dysplasia and/orpituitary hormone deficiency. Arquivos Brasileiros deEndocrinologia and Metabologia, 54, 482-487
[8]Davis S W, Castinetti F, Carvalho L R, Ellsworth B S, PotokMA, Lyons R H, BrinkmeierML, Raetzman LT, CarninciP, Mortensen A H, et al. 2010. Molecular mechanismsof pituitary organogenesis: in search of novel regulatorygenes. Molecular and Cellular Endocrinology, 323,4-19
[9]Duboc V, Logan M P. 2011. Pitx1 is necessary for normalinitiation of hindlimb outgrowth through regulation ofTbx4 expression and shapes hindlimb morphologies viatargeted growth control. Development, 138, 5301-5309
[10]Elens L, Becker M L, Haufroid V, Hofman A, Visser L E,Uitterlinden A G, Stricker B C, van Schaik R H. 2011.Novel CYP3A4 intron 6 single nucleotide polymorphismis associated with simvastatin-mediated cholesterolreduction in the Rotterdam study. Pharmacogeneticsand Genomics, 21, 861-866
[11]FaradayN, Yanek L R, Yang X P,Mathias R, Herrera-GaleanoJ E, Suktitipat B, Qayyum R, Johnson A D, Chen M H,Tofler G H, et al. 2011. Identification of a specific intronicPEAR1 gene variant associated with greater plateletaggregability and protein expression. Blood, 8, 3367-3375
[12]Gama L T, Bressan M C. 2011. Biotechnology applicationsfor the sustainable management of goat geneticresources. Small Ruminant Research, 98, 133-146
[13]Gao Y, Zhang Y H, Zhang S, Li F, Wang S, Dai L, Jiang H,Xiao S, Liu D, Sun B, et al. 2011. Association of AFABPgene polymorphism in intron 1 with meat qualitytraits in Junmu No. 1 white swine. Gene, 487, 170-173
[14]Greenwood T A, Kelsoe J R. 2003. Promoter and intronicvariants affect the transcriptional regulation of thehuman dopamine transporter gene. Genome, 82, 511-520
[15]Groeneveld L F, Lenstra J A, Eding H, Toro M A, Scherf B,Pilling D, Negrini R, Finlay E K, Jianlin H, Groeneveld E,et al. 2010. The GLOBALDIV consortium. Geneticdiversity in farm animals - a review. Animal Genetics,41, 6-31
[16]Hayashi T, Motoishi M, Yazawa S, Itomi K, TanegashimaC, Nishimura O, Agata K, Tarui H A. 2011. LIMhomeoboxgene is required for differentiation of Wntexpressingcells at the posterior end of the planarianbody. Development, 138, 3679-3688
[17]Kraisin S, Naka I, Patarapotikul J, Nantakomol D, NuchnoiP, Hananantachai H, Tsuchiya N, Ohashi J. 2011.Association of ADAMTS13 polymorphism withcerebral malaria. Malaria Journal, 10, 366.
[18]Kobayashi K, Yuliwulandari R, Yanai H, Naka I, Lien L T,Hang N T, Hijikata M, Keicho N, Tokunaga K. 2012.Association of TLR polymorphisms with developmentof tuberculosis in Indonesian females. Tissue Antigens,79, 190-197
[19]Kumar D, Deb I, Chakraborty J, Mukhopadhyay S, Das S.2011. A polymorphism of the CREB binding protein(CREBBP) gene is a risk factor for addiction. BrainResearch, 1406, 59-64
[20]Lan X Y, Pan C Y, Chen H, Zhang C L, Li J Y, Zhao M, LeiC Z, Zhang A L, Zhang L. 2007. An AluI PCR-RFLPdetecting a silent allele at the goat POU1F1 locus andits association with production traits. Small RuminantResearch, 73, 8-12
[21]Lanctôt C, Gauthier Y, Drouin J. 1999. Pituitary homeobox1 (Ptx1) is differentially expressed during pituitarydevelopment. Endocrinology, 140, 1416-1422
[22]Lamberet G, Delacroix-Buchet A, Degas C. 2001. Intensityof initial lipolysis in goats’ milk and the perception of“goaty” Aroma in the cheese. In: Proceedings of theTechnical Symposium, 7th Intenational Conference onGoats: Recent Advances on Goat Milk Quality, RawMaterial for Cheesemaking. Poitiers, France. pp. 130-139
[23]Li S, Crenshaw III E B, Rawson E J, Simmons DM, SwansonLW, Rosenfeld M G. 1990. Dwarf locus mutants lackingthree pituitary cell types result from mutations in thePOU-domain gene Pit-1 Nature, 347, 528-533.
[24]Liu D X, Lobie P E. 2007. Transcriptional activation of p53by Pitx1. Cell Death and Differentiation, 14, 1893-1907
[25]Liu J B, Lan X Y, Xu Y, Li Z J, Lei C Z, Chen H. 2011.Combined effects of three novel SNPs within goatLHX3 gene on milk performance. Genes and Genomics,33, 549-556
[26]Maèeková S, Bernasovský I, Gabriková D, Bô?iková A,Bernasovská J, Boroòová I, Behulová R, Svíèková P,Petrejèíková E, Soták M, et al. 2012. Association of theFTO rs9939609 polymorphism with obesity in Roma/Gypsy population. American Journal of PhysicalAnthropology, 147, 30-34
[27]MarcilA, Dumontier E, ChamberlandM, Camper SA, DrouinJ. 2003. Pitx1 and Pitx2 are required for development ofhindlimb buds. Development, 130, 45-55
[28]Msalya G, Shimogiri T, Nishitani K,Okamoto S, Kawabe K,Minesawa M, Maeda Y. 2010. Indels within promoterand intron 1 of bovine prion protein gene modulate thegene expression levels in the medulla oblongata of twoJapanese cattle breeds. Animal Genetics, 41, 218-221
[29]Nei M, Roychoudhury A K. 1974. Sampling variances ofheterozygosity and genetic distance. Genetics, 76, 379-390
[30]Ou Z, Martin D M, Bedoyan J K, Cooper M L, Chinault A C,Stankiewicz P, Cheung S W. 2008. Branchiootorenalsyndrome and oculoauriculovertebral spectrum featuresassociated with duplication of SIX1, SIX6, and OTX2resulting from a complex chromosomal rearrangement.American Journal of Medical Genetics (Part A), 146A,2480-2489
[31]Peacock C, Sherman D M. 2010. Sustainable goatproduction-some global perspectives. Small RuminantResearch, 89, 70-80
[32]Pedersen L D, Sørensen AC, Berg P. 2009. Marker-assistedselection can reduce true as well as pedigree-estimatedinbreeding. Journal of Dairy Science, 92, 2214-2223
[33]Pelgas B, Isabel N, Bousquet J. 2004. Efficient screeningfor expressed sequence tag polymorphisms (ESTPs)by DNA pool sequencing and denaturing gradient gelelectrophoresis (DGGE) in spruces. MolecularBreeding, 13, 263-279
[34]Pfäffle R, Klammt J. 2011. Pituitary transcription factors inthe aetiology of combined pituitary hormonedeficiency. Best Practice and Research: ClinicalEndocrinology and Metabolism, 25, 43-60
[35]Poulin G, Lebel M, Chamberland M, Paradis FW, Drouin J.2000. Specific protein-protein interaction between basichelix-loop-helix transcription factors and homeoproteinsof the Pitx family. Molecular and Cellular Biology, 20,4826-4837
[36]Schennink A, Bovenhuis H, Léon-Kloosterziel K M, vanArendonk J A, Visker M H. 2009. Eff ect ofpolymorphisms in the FASN, OLR1, PPARGC1A, PRLand STAT5A genes on bovine milk-fat composition.Animal Genetics, 40, 909-916
[37]Snabboon T, Plengpanich W, Buranasupkajorn P,Khwanjaipanich R, Vasinanukorn P, SuwanwalaikornS, Khovidhunkit W, Shotelersuk V. 2008. A novelgermline mutation, IVS4+1G>A, of the POU1F1 geneunderlying combined pituitary hormone deficiency.Hormone Research, 69, 60-64
[38]Szeto D P, Rodriguez-Esteban C, Ryan A K, O’Connell S M,Liu F, Kioussi C, Gleiberman A S, Izpisúa-Belmonte J C,Rosenfeld M G. 1999. Role of the Bicoid-relatedhomeodomain factor Pitx1 in specifying hindlimbmorphogenesis and pituitary development. Genes andDevelopment, 13, 484-494
[39]Szeto D P, Ryan A K, O’Connell S M, Rosenfeld M G. 1996.P-OTX: a PIT-1-interacting homeodomain factorexpressed during anterior pituitary gland development Proceedings of the National Academy of the UnitedStates of America, 93, 7706-7710
[40]Tang G, Li X, Plastow G, Moore S S, Wang Z. 2011.Developing marker-assisted models for evaluatinggrowth traits in Canadian beef cattle geneticimprovement. Livestock Science, 138, 62-68
[41]Tremblay J J, Lancto T C, Drouin J. 1998. The pan-pituitaryactivator of transcription, Ptx1 (pituitary homeobox 1),acts in synergy with SF-1 and Pit-1 and is an upstreamregulator of the lim-homeodomain gene Lim3/Lhx3 Molecular Endocrinology, 12, 428-441
[42]Vivenza D, Godi M, Faienza M F, Mellone S, Moia S, RapaA, Petri A, Bellone S, Riccomagno S, Cavallo L, et al.2011. A novel HESX1 splice mutation causes isolatedGH deficiency by interfering with mRNA processing.European Journal of Endocrinology, 164, 705-713
[43]West B E, Parker G E, Savage J J, Kiratipranon P, Toomey KS, Beach L R, Colvin S C, Sloop KW, Rhodes S J. 2004.Regulation of the follicle-stimulating hormone beta geneby the LHX3 LIM-homeodomain transcription factor.Endocrinology, 145, 4866-4879
[44]Yeh F C, Yang R C, Boyle T. 1999. Microsoft Windows-Based Freeware for Population Genetic Analysis.POPGENE. Release 1.31. University of Alberta,Edmonton.
