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| Polymorphism of ADRB3 Gene and Its Association Analysis with Reproductive Traits in Hu Sheep (Ovis aries) |
| ZHU Zhen, MENG Xu-Ming, LI Xiao-Tong, LIU Tong, KOU Zhi-Yuan, CANG Zhen, MAO Da-Gan* |
| College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China |
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Abstract The adrenoceptor beta 3 (ADRB3) gene encodes a G protein-coupled membrane surface receptor with multiple roles in regulating lipolysis and energy expenditure. The aim of this study was to investigate the single nucleotide polymorphisms (SNP) in the untranslated region (UTR) of the ADRB3 gene by Sanger sequencing of PCR products and MassARRAY, and analyze their association with reproductive traits in Hu sheep (Ovis aries). The results showed that 4 SNP loci were identified in the UTR of the ADRB3 gene: g.42G>T, g.2377G>T, g.2501T>A and g.2622G>A. Each of these loci exhibits 3 genotypes and the dominant genotypes were all TT except for g.2622G>A whose dominant genotype was GA. All SNPs showed middle polymorphism (0.25<PIC<0.5) except g.42G>T (PIC<0.25). χ2 tests indicated that the genotype distributions of all SNPs were in Hardy-Weinberg equilibrium (P>0.05). Association analysis revealed that for the g.42 G>T locus, the litter size in parity 1 was significantly higher in individuals with the GG genotype than those with the TT genotype, which was significantly higher than the GT genotype (P<0.05). The litter size in parity 2 was significantly higher in individuals with the GG genotype than those with the GT and TT genotypes. The lambing interval of parity 2~3 in individuals with the GT and TT genotypes was significantly shorter than those with the GG genotype (P<0.05). For the g.2377G>T locus, the lambing interval of parity 2~3 in individuals with the GT genotype was significantly shorter than those with the TT genotype (P<0.05). At the g.2501T>A locus, the litter size in parity 4 was significantly higher in individuals with the TT and TA genotype than those with the AA genotype (P<0.05). For the g.2622G>A locus, the litter size in parity 3 was significantly higher in individuals with the GA genotype than those with the AA genotype (P<0.05). Diplotype analysis showed that 5 haplotypes and 15 diplotypes were detected at 4 SNPs loci in the experimental population. Association analysis of 9 (frequency>0.05) haplotypes with reproductive traits revealed that the individuals with the H5H5 (TTTTTTGG) diplotypes had higher litter size. In conclusion, the ADRB3 gene can be used as a candidate gene for molecular markers of reproductive traits. This study provides a reference for accelerating the breeding process of high fertility Hu sheep.
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Received: 21 April 2025
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Corresponding Authors:
*maodagan@njau.edu.cn
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[1] 胡江. 2010. 牛ADRB3、CAPN3和CAPN4基因多态性及其对生长和胴体性状的影响[D]. 博士学位论文, 甘肃农业大学, 导师: 赵兴绪, 罗玉柱, pp. 115.
(Hu J. 2010. Polymorphism of bovine ADRB3, CAPN3, and CAPN4 genes and their effects on growth and carcass traits[D]. Thesis for Ph.D., Gansu Agricultural University, Supervisor: Zhao X X, Luo Y Z, pp. 115.)
[2] 贾超. 2018. GDF9基因在雌性绵羊生殖器官的表达及其对产羔率调控的研究[D]. 硕士学位论文, 吉林农业大学, 导师: 姜怀志, pp. 53.
(Jia C. 2018. Expression of GDF9 gene in the reproductive organs of female sheep and its regulation on lambing rate[D]. Thesis for M.S. Jilin Agricultural University, Supervisor: Jiang H Z, pp. 53.)
[3] 王昊天, 赵瑞霞, 张天闻, 等. 2025.湖羊产羔性状和生长性状的分子标记研究进展[J]. 中国畜牧杂志, 1-14.
(Wang H T, Zhao R X, Zhang T W, et al.2025. Advances in molecular markers for litter size and growth traits in Hu sheep[J]. Chinese Journal of Animal Science, 1-14.)
[4] 王明远, 朱梦婷, 邵焱焱, 等. 2021.绵羊MTNR1A基因多态性及其单倍型与产羔数的相关性[J]. 农业生物技术学报, 29(7): 1303-1312.
(Wang M Y, Zhu M T, Shao Y Y, et al.2021. Polymorphisms and haplotypes of MTNRlA gene and their association with litter size in sheep (Ovis aries)[J]. Journal of Agricultural Biotechnology, 29(7): 1303-1312.)
[5] 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.)
[6] 张艳丽, 郭佳禾, 姚晓磊, 等. 2022. 湖羊繁殖性状的调控机制研究进展[J]. 南京农业大学学报, 45(5): 1032-1040.
(Zhang Y L, Guo J H, Yao X L, et al.2022. Research progress on the regulation mechanism of Hu sheep reproductive traits[J]. Journal of Nanjing Agricultural University, 45(5): 1032-1040.)
[7] Akey J, Jin L, Xiong M.2001. Haplotypes vs single marker linkage disequilibrium tests: What do we gain[J]. European Journal of Human Genetics, 9(4): 291-300.
[8] Ali A, Javed K, Zahoor I, et al.2023. Identification of polymorphisms in the MSTN and ADRB3 genes associated with growth and ultrasound carcass traits in Kajli sheep[J]. Animal Biotechnology, 34(4): 847-862.
[9] Baturin A K, Sorokina E Y, Pogozheva A V, et al.2016. The investigation the combined effect of SNP rs9939609 (gene FTO) and rs4994 (gene ADRB3) polymorphisms on risk of obesity[J]. Voprosy Pitaniia, 85(4): 29-34.
[10] Calvani M, Dabraio A, Subbiani A, et al.2020. β3-adrenoceptors as putative regulator of immune tolerance in cancer and pregnancy[J]. Frontiers in Immunology, 11: 2098.
[11] Cao W, Luttrell L M, Medvedev A V, et al.2000. Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation[J]. The Journal of Biological Chemistry, 275(49): 38131-38134.
[12] Fırat E, Aybek Z, Akgün Ş, Küçüker K,et al.2020. Relation of ADRB3, GEF, ROCK2 gene polymorphisms to clinical findings in overactive bladder[J]. World Journal of Urology, 38(10): 2571-2575.
[13] Forrest R H, Hickford J G.2000. Rapid communication: Nucleotide sequences of the bovine, caprine, and ovine beta3-adrenergic receptor genes[J]. Journal of Animal Science, 78(5): 1397-1398.
[14] Forrest R H, Hickford J G, Hogan A, et al.2003. Polymorphism at the ovine beta3-adrenergic receptor locus: Associations with birth weight, growth rate, carcass composition and cold survival[J]. Animal Genetics, 34(1): 19-25.
[15] Forrest R H, Hickford J G, Frampton C M.2007. Polymorphism at the ovine beta3-adrenergic receptor locus (ADRB3) and its association with lamb mortality[J]. Journal of Animal Science, 85(11): 2801-2806.
[16] Forrest R H, Itenge-Mweza T O, McKenzie G W, et al.2009. Polymorphism of the ovine beta3-adrenergic receptor gene (ADRB3) and its association with wool mean staple strength and yield[J]. Animal Genetics, 40(6): 958-962.
[17] Gauthier C, Leblais V, Kobzik L, et al.1998. The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle[J]. The Journal of Clinical Investigation, 102(7): 1377-1384.
[18] Grillo, A. Turi, F. Licciulli, et al.2010. UTRdb and UTRsite (RELEASE 2010): A collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs[J]. Nucleic Acids Research, 38(2010): D75-80.
[19] Ji X, Cao Z, Hao Q, et al.2023. Effects of new mutations in BMPRIB, GDF9, BMP15, LEPR, and B4GALNT2 genes on litter size in sheep[J]. Veterinary Sciences, 10(4): 258.
[20] Kozak M.1986. Point mutations that create initiation codons can alter the properties of eukaryotic mRNAs[J]. Molecular and Cellular Biology, 6(9): 3253-3263.
[21] Macdonald P M, Struhl G.1988. Cis-acting sequences responsible for anterior localization of bicoid mRNA in Drosophila embryos[J]. Nature, 336: 595-598.
[22] Martin K C, Ephrussi A.2009. mRNA localization: Gene expression in the spatial dimension[J]. Cell, 136: 719-730.
[23] Mayo O.2008. A century of Hardy-Weinberg equilibrium[J]. Twin Research and Human Genetics, 11(3): 249-256.
[24] Mei C G, Gui L S, Wang H C, et al.2018. Polymorphisms in adrenergic receptor genes in Qinchuan cattle show associations with selected carcass traits[J]. Meat Science, 135: 166-173.
[25] Mignone F, Gissi S.2006. Untranslated regions of mRNAs[J]. Genome Biology, 7(3): 219.
[26] Nardini P, Zizi V, Molino M, et al.2024. Protective effects of beta-3 adrenoceptor agonism on mucosal integrity in hyperoxia-induced ileal alterations[J]. Antioxidants (Basel, Switzerland), 13(7): 863.
[27] Ray D, Kazan H, Cook K B, et al.2013. A compendium of RNA-binding motifs for decoding gene regulation[J]. Nature, 499: 172-177.
[28] Rouget C, Bardou M, Breuiller-Fouché M, et al.2005.Beta3-adrenoceptor is the predominant beta-adrenoceptor subtype in human myometrium and its expression is up-regulated in pregnancy[J]. Journal of Clinical Endocrinology and Metabolism[J]. 90(3): 1644-1650.
[29] Trochu J N, Leblais V, Rautureau Y, et al.1999. Beta 3-adrenoceptor stimulation induces vasorelaxation mediated essentially by endothelium-derived nitric oxide in rat thoracic aorta[J]. British Journal of Pharmacology, 128(1): 69-76.
[30] Velazquez-Roman J, Angulo-Zamudio U A, León-Sicairos N, et al.2021. Association of FTO, ABCA1, ADRB3, and PPARG variants with obesity, type 2 diabetes, and metabolic syndrome in a Northwest Mexican adult population[J]. Journal of Diabetes Complications, 35(11): 108025.
[31] Wan Z, Yang H, Chen P, et al.2022. The novel competing endogenous long noncoding RNA SM2 regulates gonadotropin secretion in the Hu sheep anterior pituitary by targeting the Oar-miR-16b/TGF-β/SMAD2 signaling pathway[J]. Cells, 11(6): 985.
[32] Xie L, Miao X, Luo Q, et al.2023. Impact of FecB mutation on ovarian DNA methylome in small-tail Han sheep[J]. Genes, 14(1): 203.
[33] Yang G, Zhou H, Hu J, et al.2009. Extensive diversity of the ADRB3 gene in Chinese sheep identified by PCR-SSCP[J]. Biochemical Genetics, 47(7-8): 498-502.
[34] Yang S, Ma H, Wang L, et al.2024. The role of β3-Adrenergic receptors in cold-induced beige adipocyte production in pigs[J]. Cells, 13(8): 719.
[35] Zafar U, Khaliq S, Ali Z, et al.2019. Adrenergic receptor beta-3 rs4994 (T>C) and liver X receptor alpha rs12221497 (G>A) polymorphism in Pakistanis with metabolic syndrome[J]. Chinese Journal of Physiology, 62(5): 196-202. |
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