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| Polymorphisms of 3'-UTR of POU1F1 Gene and Its Association with Growth Traits in Shaanbei White Cashmere Goats (Capra hircus) |
| YANG Han1*, ZHANG Yang-Hai1*, WANG Min1, KANG Yu-Xin1, ZHU Hai-Jing2,3, LAN Xian-Yong1, QU Lei2,3, YAN Hai-Long1,2,3, PAN Chuan-Ying1** |
1 College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China;;
2 Life Science Research Center, Yulin University, Yulin 719000, China;
3 Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Yulin University, Yulin 719000, China |
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Abstract Pituitary specific transcription factor 1 (POU1F1) is a member of the POU family (pituitary specific transcription factor, Pit-1; octameric binding protein, Oct-1 and Oct-2; caenorhabedit Ⅰ nematode nerve Unc-86), who is a positive transcription factor regulating pituitary hormone-related genes and plays an important role in the growth and development of mammals. Thus, POU1F1 gene is extensively considered as a candidate gene for growth performance in goats (Capra hircus). In order to verify the genetic effects of flanking region of POU1F1 gene on the growth traits in Shaanbei white cashmere (SBWC) goats, the genetic polymorphisms of 3'-untranslated region (3'-UTR) within POU1F1 gene was detected in all adult SBWC goats (n=621) by direct DNA sequencing method, and the associations of different genotypes of polymorphisms and 9 kinds of growth traits in SBWC goats were analyzed. Sequencing results showed that a single nucleotide polymorphism (SNP), named NC_030808.1:g.34235967T>C and located at position 164 of the 3'-UTR within POU1F1 gene (c.876+164A>G), was identified in these SBWC population. The frequencies of alleles A and G of this locus were 0.894 and 0.106, respectively; the number of effective alleles (Ne) was 1.235; the homozygosity (Ho) was 0.810; the heterozygosity (He) was 0.190; and the polymorphism information content (PIC) was 0.172 and the loci was low polymorphisms. The values of these genetic polymorphism indexes reflect the inferior degree of genetic variation in this population, and the value of PIC belongs to the low PIC (PIC<0.25). In addition, the c.876+164A>G locus conformed to Hardy-Weinberg equilibrium (P>0.05) in the SBWC goat population. The further association analysis results demonstrated that the c.876+164A>G locus was significantly associated with the body length and cannon circumference in SBWC goats (P<0.05). However, there were no significant effects from the SNP for other growth traits, including body weight, body height, height at hip cross, chest circumference, chest depth, chest width and hip width. The individuals with AG genotype were significantly superior to other genotypes in both body length (P=0.047) and cannon circumference (P=0.035) in this population. Thus, the AG genotype could be considered as a positive genotype for this SNP in SBWC goats. In addition, the mutation in 3'-UTR could not only affect its binding to target miRNA, but also change transcription factor binding sites. Here, bioinformatics prediction of transcription factors on this SNP was performed by Genomatix MatInspector software v3.11, and analysis result indicated that the binding of the transcription factor MEL1 (myelodysplasia syndrome 1/ecotropic viral integration site1-like gene 1) with POU1F1 gene was affected when this locus mutated. MEL1, also called PRDM16, could simultaneously activate and inhibit gene transcription, which might be related to multiple transcriptional domains in gene structure. Therefore, when the A allele was replaced by G allele at the c.876+164A>G locus, the binding of the MEL1 with POU1F1 gene was hampered and the inhibition of POU1F1 gene was discharged, which might affect growth and development of individuals by facilitating the expression level of POU1F1 gene. These research results unveiled that the c.876+164A>G had strong effects on body length and cannon circumference of SBWC goats, which could be used as a candidate marker for marker assisted selection of greater growth performance and would provide scientific information for the genetic breeding and improvement in goat industry.
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Received: 21 January 2019
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Corresponding Authors:
chuanyingpan@nwafu.edu.cn
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[1] 高鸿蒙, 张秀英, 张慧泽, 等. 2019. 乌珠穆沁羊LPL基因第3外显子多态性与肉质性状的关联分析[J]. 农业生物技术学报, 27(3): 449-455.
(Gao H M, Zhang X Y, Zhang H Zet al.2019. Association analysis between polymorphism in the exon 3 of LPL gene and meat quality traits in Ujimqin sheep (Ovis aries)[J]. Journal of Agricultural Biotechnology, 27(3): 449-455.)
[2] 刘阿云. 2018. 陕北白绒山羊生产性能研究进展[J]. 中国草食动物科学, 38(02): 65-68.
(Liu A Y.2018. Progress in the production performance of Shaanbei white cashmere goat[J]. China Herbivore Science, 38(02): 65-68.)
[3] 罗卫星, 蔡惠芬, 王兴群, 等. 2011. 山羊垂体转录因子POU1F1基因多态性及其与屠宰性状相关性研究[J]. 中国畜牧杂志, 47(09): 5-9.
(Luo W X, Cai H F, Wang X Q, et al.2011. Polymorphism of POU1F1 gene in goat pituitary and its correlation with carcass traits[J]. Chinese Journal of Animal Science, 47(09): 5-9.)
[4] 宋娜娜, 柴志欣, 胡丹, 等. 2016. 西藏牦牛POU1F1基因的多态性及其与生长性状的相关性分析[J]. 西南农业学报, 29(12): 2994-3000.
(Song N N, Chai Z X, Hu D, et al.2016. Polymorphism of POU1F1 gene in Tibetan Yak and its correlation with growth traits[J]. Southwest China Journal of Agricultural Sciences, 29(12): 2994-3000.)
[5] 吴森, 桂林生, 昝林森. 2018. 南阳牛ATP5B基因启动子区域多态性与生长性状的关联性研究[J]. 农业生物技术学报, 26(9): 1535-1545.
(Wu S, Gui L S, Zan L S.2018. Association of polymorphisms in ATP5B promoter region with growth traits of Nanyang cattle (Bos taurus)[J]. Journal of Agricultural Biotechnology, 26(9): 1535-1545.)
[6] 张娟, 母童, 蔡正云, 等. 2018. UCP基因多态性及与黑安格斯牛生长性状的关联分析[J]. 农业生物技术学报, 26(7): 1195-1202.
(Zhang J, Mu T, Cai Z Y, et al.2018. The polymorphisms of UCP gene and its association with growth traits of black Angus cattle (Bos taurus)[J]. Journal of Agricultural Biotechnology, 26(7): 1195-1202.)
[7] 周寒, 陈继明, 刘瑞霞, 等. 2012. 陕北白绒山羊产业发展现状调查研究[J]. 畜牧与饲料科学, 33(04): 64-65.
(Zhou H, Chen J M, Liu R X, et al.2012. Investigation of development status of Shaanbei white cashmere goat industry[J]. Animal Husbandry and Feed Science, 33(04): 64-65.)
[8] 赵宪林, 曹少杰, 王俊全. 2018. MC4R基因多态性及基因型组合与藏羊生长性状的关联分析[J]. 农业生物技术学报, 26(3): 429-436.
(Zhao X L, Cao S J, Wang J Q.2018. Association analysis of MC4R gene polymorphisms and genotype combination with growth traits of Tibetan sheep (Ovis aries)[J]. Journal of Agricultural Biotechnology, 26(3): 429-436.)
[9] 赵宗胜, 李大全, 代军才, 等. 1999. 对肉羊线性外貌Fuzzy综合评判的探讨[J]. 石河子大学学报(自然科学版), 3(1): 21-24.
(Zhao Z S, Li D Q, Dai J C, et al.1999. A comprehensive judgement of mutton sheep with Fuzzy mathematics[J]. Journal of Shihezi University (Natural Science Edition), 3(1): 21-24.)
[10] An X, Song Y, Hou J, et al.2016. Identification of a functional SNP in the 3'-UTR of caprine MTHFR gene that is associated with milk protein levels[J]. Animal Genetics, 47(4): 499-503.
[11] Baş F, Abalı ZY, Toksoy G, et al.2018. Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: Case report and review of possible mechanisms[J]. Hormones (Athens), 17(4): 581-588.
[12] Cartharius K, Frech K, Grote K, et al.2005. MatInspector and beyond: Promoter analysis based on transcription factor binding sites[J]. Bioinformatics, 21(13): 2933-2942.
[13] Cui Y, Yan H, Wang K, et al.2018. Insertion/deletion within the KDM6A gene is significantly associated with litter size in goat[J]. Frontiers in Genetics, 9: 91.
[14] Daga C, Paludo M, Luridiana S, et al.2013. Identification of novel SNPs in the Sarda breed goats POU1F1 gene and their association with milk productive performance[J]. Molecular Biology Reports, 40(4): 2829-2835.
[15] Fei L R, Huang W J, Wang Y, et al.2019. PRDM16 functions as a suppressor of lung adenocarcinoma metastasis[J]. Journal of Experimental & Clinical Cancer Research, 38(1): 35.
[16] Feng T, Chu M X, Cao G L, et al.2012. Polymorphisms of caprine POU1F1 gene and their association with litter size in Jining Grey goats[J]. Molecular Biology Reports, 39(4): 4029-4038.
[17] Frühbeck G, Sesma P, Burrell MA.2009. PRDM16: The interconvertible adipo-myocyte switch[J]. Trends in Cell Biology, 19(4): 141-146.
[18] Hou J, An X, Song Y, et al.2015. Two mutations in the caprine MTHFR 3'UTR regulated by microRNAs are associated with milk production traits[J]. PLoS ONE, 10(7): e0133015.
[19] Iannaccone M, Cosenza G, Pauciullo A, et al.2018. The SNP g.4667G>A at 3'-UTR of IFNG gene is associated with susceptibility to bovine tuberculosis in Mediterranean water buffalo (Bubalus bubalis)[J]. Animal Genetics, 49(5): 496-497.
[20] Kajimura S, Seale P, Tomaru T, et al.2008. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex[J]. Genes & Development, 22(10): 1397-1409.
[21] Lan X Y, Pan C Y, Chen H, et al.2007a. An AluⅠ PCR-RFLP detecting a silent allele at the goat POU1F1 locus and its association with production traits[J]. Small Ruminant Research, 73(1-3): 8-12.
[22] Lan X Y, Pan C Y, Chen H, et al.2007b. DdeⅠ polymorphism in coding region of goat POU1F1 gene and its association with production traits[J]. Asian Australasian Journal of Animal Sciences, 20(9): 1342-1348.
[23] Lan X Y, Shu J H, Chen H, et al.2009. A PstⅠ polymorphism at 3'UTR of goat POU1F1 gene and its effect on cashmere production[J]. Molecular Biology Reports, 36(6): 1371-1374.
[24] Li S, Crenshaw E B, Rawson E J, et al.1990. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene PIT-1[J]. Nature, 347(6293): 528-533.
[25] Mayr C.2018. What Are 3' UTRs Doing?[J]. Cold Spring Harbor Perspectives in Biology, a034728.
[26] Miltiadou D, Hager-Theodorides A L, Symeou S, et al.2017. Variants in the 3' untranslated region of the ovine acetyl-coenzyme A acyltransferase 2 gene are associated with dairy traits and exhibit differential allelic expression[J]. Journal of Dairy Science, 100(8): 6285-6297.
[27] Nishikata I, Nakahata S, Saito Y, et al.2011. Sumoylation of MEL1S at lysine 568 and its interaction with CtBP facilitates its repressor activity and the blockade of G-CSF-induced myeloid differentiation[J]. Oncogene, 30(40): 4194-4207.
[28] Nishikata I, Sasaki H, Iga M, et al.2003. A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation[J]. Blood, 102(9): 3323-3332.
[29] Ozmen O, Kul S, Unal E O.2014. Polymorphism of sheep POU1F1 gene exon 6 and 3'UTR region and their association with milk production traits[J]. Iranian Journal of Veterinary Research, 15(4): 331-335.
[30] Pan C, Lan X, Chen H, et al.2008. A TaqI PCR-RFLP detecting a novel SNP in exon 2 of the bovine POU1F1 gene[J]. Biochemical Genetics, 46(7-8): 424-432.
[31] Seong J, Oh J D, Cheong I C, et al.2011. Association between polymorphisms of Myf5 and POU1F1 genes with growth and carcass traits in Hanwoo (Korean cattle)[J]. Genes & Genomics, 33(4): 425-430.
[32] Scully K M, Rosenfeld M G.2002. Pituitary development: Regulatory codes in mammalian Organogenesis[J]. Science, 295(5563): 2231-2235.
[33] Stachowiak M, Szydlowski M, Flisikowski K, et al.2014. Polymorphism in 3' untranslated region of the pig PPARA gene influences its transcript level and is associated with adipose tissue accumulation[J]. Journal of Animal Science, 92(6): 2363-2371.
[34] Steinfelder H J, Radovick S, Wondisford F E.1992. Hormonal regulation of the thyrotropin beta-subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1[J]. Proceedings of The National Academy of Sciences of the USA, 89(13): 5942-5945.
[35] van Laere A S, Nguyen M, Braunschweig M, et al.2003. A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig[J]. Nature, 425(6960): 832-836.
[36] Wang X, Yang Q, Wang K, et al.2017. A novel 12-bp indel polymorphism within the GDF9 gene is significantly associated with litter size and growth traits in goats[J]. Animal Genetics, 48(6): 735-736.
[37] Wang H, Huang W, Yu X, et al.2019. Two prostate cancer-associated polymorphisms in the 3'UTR of IGF1R influences prostate cancer susceptibility by affecting miRNA binding[J]. Oncology Reports, 41(1): 512-524.
[38] Wu W, Wu L, Zhu M, et al.2018. miRNA mediated noise making of 3'UTR mutations in cancer[J]. Genes-Basel, 9(11): 545.
[39] Xiang G, Ren J, Hai T, et al.2018. Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs[J]. Cellular and Molecular Life Sciences, 75(24): 4619-4628.
[40] Zang L, Wang Y, Sun B, et al.2016. Identification of a 13 bp indel polymorphism in the 3'-UTR of DGAT2 gene associated with backfat thickness and lean percentage in pigs[J]. Gene, 576(2): 729-733.
[41] Zhao Q,Davis M E,Hines H C.2004. Associations of polymorphisms in the Pit-1 gene with growth and carcass traits in Angus beef cattle[J]. Journal of Animal Science, 82(8): 2229-2233.
[42] Zhang B, Chang L, Lan X, et al.2018a. Genome-wide definition of selective sweeps reveals molecular evidence of trait-driven domestication among elite goat (Capra species) breeds for the production of dairy, cashmere, and meat[J]. Gigascience, 7(12): 1-11.
[43] Zhang Y, Cui Y, Zhang X, et al.2018b. Pig StAR: mRNA expression and alternative splicing in testis and Leydig cells, and association analyses with testicular morphology traits[J]. Theriogenology, 118: 46-56. |
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