Tissue Expression, SNP Scanning of GRB10 Gene, and Correlation Analysis with Blood Physiological Indexes in Hu Sheep (Ovis aries)
ZHANG Qi1, YANG Xiao-Bin1, LI Xiao-Long1, YAN Cheng-Qi1, PU Meng-Ru1, KONG De-Wen2, WANG Wei-Min1, WANG Xin-Ji3, LI Kai-Dong4, LI Fa-Di1, TIAN Hui-Bin1,*
1 College of Pastoral Agriculture Science and Technology/State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems,Lanzhou University, Lanzhou 730020, China; 2 College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China; 3 Minqin County Animal Husbandry and Veterinary Station, Minqin 733399, China; 4 Minqin County Zhongxing Town Agricultural and Rural Comprehensive Service Center, Minqin 733399, China
Abstract：Growth factor receptor-bound protein 10 (GRB10), as a key gene regulating growth and development as well as energy metabolism, plays a significant role in immune regulation. Blood physiological indicators serve as important reference criteria for assessing animal's health status, In practical production, monitoring blood physiological indicators enables timely understanding of animal's health status and immune capacity,while alterations in immune performance also influence blood physiological indicators. In this study, a total of 1 086 healthy Hu sheep (Ovis aries) with clear pedigrees were selected as research subjects. The correlations among their hematological and physiological indices were analyzed, and the effects of GRB10 gene polymorphisms on these indices were investigated. Results revealed that there were strong positive correlations among similar blood physiological indicators, weaker correlations between platelet traits and red blood cell/white blood cell traits, and significant negative correlations among white blood cell-related traits. The coefficient of variation for blood physiological indicators in the experimental group ranged from 6.50% to 66.67%, indicating high variability. PCR amplification, Sanger sequencing, and AQP genotyping of the GRB10 gene identified the mutation site GRB10 g.6478288 G>A located in the sixth intron, exhibiting moderate polymorphism.The association analysis results indicated that individuals with the GG genotype exhibit significantly higher mean corpuscular hemoglobin concentration (MCHC), total white blood cell count (WBC), lymphocyte count (LYMPH1), eosinophil count (EO1), and reticulocyte hemoglobin equivalent (RET_He) were significantly higher than those of AA genotype individuals (P<0.05). Conversely, GG genotype individuals exhibited significantly lower hematocrit (HCT), mean corpuscular volume (MCV), and red blood cell hemoglobin (RBC_He) levels compared to AA genotype individuals (P<0.05). In summary, the GRB10 g.6478288 G>A variant may serve as a molecular marker for sheep-related blood physiological indicators. This study provides theoretical guidance for enhancing sheep immune performance and increasing breeding efficiency, while offering scientific basis for disease prevention and treatment.
张琪, 杨晓斌, 李晓龙, 闫成琪, 蒲萌茹, 孔得文, 王维民, 王新基, 李开栋, 李发弟, 田慧彬. 湖羊GRB10基因组织表达、SNP扫描及其与血液生理指标关联分析[J]. 农业生物技术学报, 2026, 34(3): 533-542.
ZHANG Qi, YANG Xiao-Bin, LI Xiao-Long, YAN Cheng-Qi, PU Meng-Ru, KONG De-Wen, WANG Wei-Min, WANG Xin-Ji, LI Kai-Dong, LI Fa-Di, TIAN Hui-Bin. Tissue Expression, SNP Scanning of GRB10 Gene, and Correlation Analysis with Blood Physiological Indexes in Hu Sheep (Ovis aries). 农业生物技术学报, 2026, 34(3): 533-542.
[1] 巩斌, 熊燊源, 李良远,等. 2015. GRB7家族蛋白的功能及研究进展[J]. 生物学杂志, 32(05): 80-83. (Gong B, Xiong S Y, Li L Y, et al.2015. Functions and research progress of GRB7 family proteins[J]. Journal of Biology, 32(05): 80-83.) [2] 林长春. 2023. 基于全基因组关联分析筛选湖羊血液生理指标的候选基因[D]. 博士学位论文, 甘肃农业大学, 导师: 张小雪, pp. 5-8. (Lin C C.2023. Candidate genes for blood physiological indicators in Hu sheep were screened based on genome-wide association analysis[D]. Thesis for Ph. D., Gansu Agricultural University, Suppervisor: Zhang X X, pp. 5-8.) [3] 秦学波, 张天浩, 葛丛丛, 等. 2023. 杜湖杂交F1代与湖羊羔羊生长性能和血液生理指标比较研究[J]. 黑龙江畜牧兽医, 65(01): 54-58. (Qin X B, Zhang T H, Ge C C, et al.2023. Comparative study on growth performance and hematological physiological indicators of F1 hybrid Du Hu lambs and Hu sheep lambs[J]. Heilongjiang Animal Husbandry and Veterinary Medicine, 65(01): 54-58.) [4] 王玉琴, 赵有璋. 2023. 波德代羊主要生理生化指标的测定和分析[J]. 甘肃畜牧兽医, 53(3): 2-4. (Wang Y Q, Zhao Y Z.2023. Determination and analysis of main physiological and biochemical indexes of boeder sheep[J]. Gansu Animal Husbandry and Veterinary Medicine, 53(3): 2-4.) [5] 杨文霞. 2017. 牛羊养殖环境污染问题与有效防控研究[J]. 甘肃畜牧兽医, 47(06): 54-55. (Yang W X.2017. Study on environmental pollution and effective prevention and control of cattle and sheep breeding[J]. Gansu Animal Husbandry and Veterinary Medicine, 47(06): 54-55.) [6] 章国永, 谢作典, 王蒙, 等. 2024. 湖羊人工授精技术研究[J]. 黑龙江动物繁殖, 32(04): 35-37+46. (Zhang G Y, Xie Z D, Wang M, et al. 2024. Research on artificial insemination techniques in Hu sheep[J]. Heilongjiang Animal Breeding, 32(04): 35-37+46.) [7] Charalambous M, Smith F M, Bennett W R, et al.2003. Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an IGF2-independent mechanism[J]. Proceedings of the National Academy of Sciences of the USA, 100(14): 8292-8297. [8] Chen C H, Li B J, Gu X H, et al.2019. Marker-assisted selection of YY supermales from a genetically improved farmed tilapia-derived strain[J]. Zoological Research, 40(2): 108-112. [9] Chinchilla-Vargas J, Kramer L M, Tucker J D, et al.2020. Genetic basis of blood-based traits and their relationship with performance and environment in beef cattle at weaning[J]. Frontiers in Genetics, 11: 717. [10] Deng Y J, Ren E H, Yuan W H, et al.2020. GRB10 and E2F3 as diagnostic markers of osteoarthritis and their correlation with immune infiltration[J]. Diagnostics, 10(3): 171. [11] Eggermann T, Begemann M, Kurth I, et al.2019. Contribution of GRB10 to the prenatal phenotype in Silver-Russell syndrome? Lessons from 7p12 copy number variations[J]. European Journal of Medical Genetics, 62(7): 103671. [12] Farooq U, Ahmed S, Liu G, et al.2024. Biochemical properties of sheep colostrum and its potential benefits for lamb survival: A review[J]. Animal Biotechnology, 35(1): 2320726. [13] Georges M.1999. Towards marker assisted selection in livestock[J]. Reproduction, Nutrition, Development, 39(5-6): 555-561. [14] Hine B C, Acton G A, Elks D J,et al.2022. Targeting improved resilience in Merino sheep-correlations between immune competence and health and fitness traits[J]. Animal, 16(7): 100544. [15] Hoffmann K, Heller R.2011. Uniparental disomies 7 and 14[J]. Best Practice & Research Clinical Endocrinology & Metabolism, 25(1): 77-100. [16] Holt L J, Siddle K.2005. GRB10 and GRB14: Enigmatic regulators of insulin action--and more?[J] Biochemical Journal, 388(Pt 2): 393-406. [17] Kabir N N, Kazi J U.2014. GRB10 is a dual regulator of receptor tyrosine kinase signaling[J]. Molecular Biology Reports, 41(4): 1985-1992. [18] Liu M, Bai J, He S, et al.2014. GRB10 promotes lipolysis and thermogenesis by phosphorylation-dependent feedback inhibition of mTORC1[J]. Cell Metabolism, 19(6): 967-80. [19] Moorwood K, Smith F M, Garfield A S, et al.2024. Imprinted Grb10, encoding growth factor receptor bound protein 10, regulates fetal growth independently of the insulin-like growth factor type 1 receptor (IGF1R) and insulin receptor (INSR) genes[J]. BMC Biology, 22(1): 127. [20] Pacheco A, Conington J, Corripio-Miyar Y, et al.2024. Genetic profile of adaptive immune traits and relationships with parasite resistance and productivity in Scottish Blackface sheep[J]. Animal, 18(2): 101061. [21] Rasheed A, Ilyas M, Khan T N, et al.2023. Study of genetic variability, heritability, and genetic advance for yield-related traits in tomato (Solanum lycopersicon MILL.)[J]. Frontiers in Genetics, 13: 1030309. [22] Sparks A M, Watt K, Sinclair R,et al.2019. The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)[J]. Public Library of Science Genetics, 15(11): e1008461. [23] Wang J, Dai H, Yousaf N, et al.1999. Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-,insulin-like growth factor I-, and insulin-mediated mitogenesis[J]. Molecular and Cellular Biology, 19(9): 6217-6228. [24] Wang Y, Ding X, Tan Z, et al.2018. Genome-wide association study for reproductive traits in a large white pig population[J]. Animal Genetics. 49(2): 127-131. [25] Xu D, Wang X, Zhang X, et al.2023. Polymorphisms in the ovine GP5 gene associated with blood physiological indices[J]. Animal Biotechnology, 34(4): 1132-1142. [26] Yan S, Du R, Yao W, et al.2024. Host-microbe interaction-mediated resistance to DSS-induced inflammatory enteritis in sheep[J]. Microbiome, 12(1): 208. [27] Yan S, Gao C, Tian K, et al.2025. Comparative population genomics analysis for chicken body sizes using genome-wide single nucleotide polymorphisms[J]. Animal Bioscience, 38(4): 600-611. [28] Yu Y, Yoon S O, Poulogiannis G,et al.2011. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling[J]. Science, 332(6035): 1322-1326. [29] Zhao X G, Zuo S X, Guo Y P, et al.2023. Carcass meat quality, volatile compound profile, and gene expression in Tan sheep under different feeding regimes[J]. Food Bioscience, 56: 103213.
