Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2, also called IMP2) plays an essential role in the development and maturation of germ cells and embryos and is a candidate gene for goat litter size, based on a previous genome-wide selective sweep analysis. In this study, the mRNA expression level of IGF2BP2 was found to be significantly higher in a single-lamb group than in a multi-lamb group. Insertions/deletions (indels) within the goat IGF2BP2 gene, including P4-Ins-13bp and P5-Del-12bp, were verified in 918 Shaanbei White Cashmere (SBWC) female goats. The minor allelic frequencies (MAFs) of P4-Ins-13bp and P5-Del-12bp loci were 0.349 and 0.295, respectively. Analysis using the Chi-square (χ2) test showed that the genotype (χ2=14.479, P=0.006) distribution of P4-Ins-13bp was significantly different between the single-lamb and multi-lamb groups. Correlation analysis demonstrated that P4-Ins-13bp was significantly associated with goat litter size (P=0.022), and individual goats with the homozygous deletion/deletion (DD) genotype produced more litters than other goats. Therefore, considered as a potential molecular marker significantly related to lambing traits, the P4-Ins-13bp mutation of the goat IGF2BP2 gene can be used in goat breeding with practical molecular marker-assisted selection (MAS) to optimize female reproduction and improve economic efficiency in the goat industry.
首次筛选、 验证山羊IGF2BP2基因的InDel位点, 确定其与山羊产羔性状的相关性及作用, 为山羊经济性状改良及新品种培育提供理论依据.
采用实时荧光定量聚合酶链式反应(qRT-PCR)方法分析IGF2BP2在单羔组和多羔组中的表达水平; 通过PCR扩增-琼脂糖凝胶电泳在918只陕北白绒母山羊中鉴定IGF2BP2基因P4-Ins-13bp和P5-Del-12bp缺失/插入位点基因型, 并进行测序以验证突变; 利用SHEsis平台分析两个位点的连锁不平衡; 采用方差分析(ANOVA)和χ2检验分析山羊IGF2BP2基因变异与产羔数的关系; 并利用在线数据库预测转录因子(TF)和突变区域序列的结合.
本研究发现, IGF2BP2的mRNA表达水平在单羔组明显高于多羔组. 在陕北白绒母山羊中验证了IGF2BP2基因内的插入/缺失(indels), 包括P4-Ins-13bp和P5-Del-12bp. χ2检验表明, P4-Ins-13bp基因型(χ2=14.479, P=0.006)在单羔和多羔组间分布差异显著; 相关分析表明, P4-Ins-13bp与山羊产仔数显着相关(P=0.022), 具有缺失/缺失(DD)基因型的山羊个体产仔数高于其他山羊. 因此, IGF2BP2基因的P4-Ins-13bp突变可作为一种潜在的与繁殖性状显著相关的分子标记, 以优化母羊繁殖力, 提高山羊产业的经济效益.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Abdoli R, Zamani P, Mirhoseini SZ, et al., 2019. Genetic parameters and trends for litter size in Markhoz goats. Rev Colomb Cienc Pec, 32(1):58–63. https://doi.org/10.17533/udea.rccp.v32n1a07
Alex R, Ramesha KP, Singh U, et al., 2018. Promoter variants of OAS1 gene are associated with reproductive performance and incidence of normal calving in cattle. Theriogenology, 108:255–261. https://doi.org/10.1016/j.theriogenology.2017.12.002
Bi Y, Feng B, Wang Z, et al., 2020. Myostatin (MSTN) gene indel variation and its associations with body traits in Shaanbei White Cashmere goat. Animals (Basel), 10(1):168. https://doi.org/10.3390/ani10010168
Biswas J, Patel VL, Bhaskar V, et al., 2019. The structural basis for RNA selectivity by the IMP family of RNA-binding proteins. Nat Commun, 10:4440. https://doi.org/10.1038/s41467-019-12193-7
Brants JR, Ayoubi TAY, Chada K, et al., 2004. Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2. FEBS Lett, 569(1–3):277–283. https://doi.org/10.1016/j.febslet.2004.05.075
Bünger L, Ronald ML, Rothschild MF, et al., 2005. Relationships between quantitative and reproductive fitness traits in animals. Philos Trans R Soc Lond B Biol Sci, 360(1459): 1489–1502. https://doi.org/10.1098/rstb.2005.1679
Chen SC, Qiu H, Liu C, et al., 2018. Relationship between IGF2BP2 and IGFBP3 polymorphisms and susceptibility to non-small-cell lung cancer: a case-control study in Eastern Chinese Han population. Cancer Manag Res, 10:2965–2975. https://doi.org/10.2147/cmar.s169222
Chennathukuzhi V, Stein JM, Abel T, et al., 2003. Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes. Mol Cell Biol, 23(18):6419–6434. https://doi.org/10.1128/mcb.23.18.6419-6434.2003
Collard BCY, Mackill DJ, 2008. Marker-assisted selection: an approach for precision plant breeding in the twenty-first century. Philos Trans Roy Soc B, 363(1491):557–572. https://doi.org/10.1098/rstb.2007.2170
Dai N, Rapley J, Angel M, et al., 2011. mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry. Genes Dev, 25(11):1159–1172. https://doi.org/10.1101/gad.2042311
E GX, Zhao YJ, Huang YF, 2019. Selection signatures of litter size in Dazu black goats based on a whole genome sequencing mixed pools strategy. Mol Biol Rep, 46(5):5517–5523. https://doi.org/10.1007/s11033-019-04904-6
Hammer NA, Hansen TVO, Byskov AG, et al., 2005. Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer. Reproduction, 130(2):203–212. https://doi.org/10.1530/rep.1.00664
Hou S, Qu DJ, Li Y, et al., 2019. XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence. Nucl Acids Res, 47(15):8239–8254. https://doi.org/10.1093/nar/gkz532
Hui YQ, Zhang YH, Wang K, et al., 2020. Goat DNMT3B: an indel mutation detection, association analysis with litter size and mRNA expression in gonads. Theriogenology, 147:108–115. https://doi.org/10.1016/j.theriogenology.2020.02.025
Jia WC, Wu XF, Li XC, et al., 2015. Novel genetic variants associated with mRNA expression of signal transducer and activator of transcription 3 (STAT3) gene significantly affected goat growth traits. Small Ruminant Res, 129:25–36. https://doi.org/10.1016/j.smallrumres.2015.05.014
Kang ZH, Jiang EH, Wang K, et al., 2019a. Goat membrane associated ring-CH-type finger 1 (MARCH1) mRNA expression and association with litter size. Theriogenology, 128:8–16. https://doi.org/10.1016/j.theriogenology.2019.01.014
Kang ZH, Zhang SH, He LB, et al., 2019b. A 14-bp functional deletion within the CMTM2 gene is significantly associated with litter size in goat. Theriogenology, 139:49–57. https://doi.org/10.1016/j.theriogenology.2019.07.026
Kin K, Nnamani MC, Lynch VJ, et al., 2015. Cell-type phylogenetics and the origin of endometrial stromal cells. Cell Rep, 10(8):1398–1409. https://doi.org/10.1016/j.celrep.2015.01.062
Kumar S, Stecher G, Tamura K, 2016. MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol, 33(7):1870–1874. https://doi.org/10.1093/molbev/msw054.
Li HX, Xu HW, Akhatayeva H, et al., 2021. Novel indel variations of the sheep FecB gene and their effects on litter size. Gene, 767:145176. https://doi.org/10.1016/j.gene.2020.145176
Li W, Liu D, Chang W, et al., 2014. Role of IGF2BP3 in trophoblast cell invasion and migration. Cell Death Dis, 5:e1025. https://doi.org/10.1038/cddis.2013.545
Liu GH, Zhu TN, Cui YJ, et al., 2015. Correlation between IGF2BP2 gene polymorphism and the risk of breast cancer in Chinese Han women. Biomed Pharmacother, 69:297–300. https://doi.org/10.1016/j.biopha.2014.12.017
Liu HB, Muhammad T, Guo YS, et al., 2019. RNA-binding protein IGF2BP2/IMP2 is a critical maternal activator in early zygotic genome activation. Adv Sci (Weinh), 6(15): 1900295. https://doi.org/10.1002/advs.201900295
Liu HF, Li HX, Mao C, et al., 2021. Insights into genetic variants within sheep IGF2BP1 and their association with litter size. Small Ruminant Res, 98:106350. https://doi.org/10.1016/j.smallrumres.2021.106350
Lu CD, Miller BA, 2019. Current status, challenges and prospects for dairy goat production in the Americas. Asian-Australas J Anim Sci, 32(8):1244–1255. https://doi.org/10.5713/ajas.19.0256
Mu QC, Wang LJ, Yu FB, et al., 2015. Imp2 regulates GBM progression by activating IGF2/PI3K/Akt pathway. Cancer Biol Ther, 16(4):623–633. https://doi.org/10.1080/15384047.2015.1019185
Muñoz M, Fernández AI, Óvilo C, et al., 2010. Non-additive effects of RBP4, ESR1 and IGF2 polymorphisms on litter size at different parities in a Chinese-European porcine line. Genet Sel Evol, 42:23. https://doi.org/10.1186/1297-9686-42-23
Pan XY, Liu SJ, Li FD, et al., 2014. Molecular characterization, expression profiles of the ovine FSHR gene and its association with litter size. Mol Biol Rep, 41(12):7749–7754. https://doi.org/10.1007/s11033-014-3666-8
Rao P, Wang H, Fang HH, et al., 2016. Association between IGF2BP2 polymorphisms and type 2 diabetes mellitus: a case-control study and meta-analysis. Int J Environ Res Public Health, 13(6):574. https://doi.org/10.3390/ijerph13060574
Ruggiu M, Speed R, Taggart M, et al., 1997. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature, 389(6646):73–77. https://doi.org/10.1038/37987
Tang Q, Zhang Y, Yang Y, et al., 2021. The KMT2A gene: mRNA differential expression in the ovary and a novel 13-nt nucleotide sequence variant associated with litter size in cashmere goats. Domest Anim Endocrinol, 74:106538. https://doi.org/10.1016/j.domaniend.2020.106538
Wang JJ, Zhao M, Xiao JP, et al., 2016. E-Cadherin, CD44v6, and insulin-like growth factor-II mRNA-Binding protein 3 expressions in different stages of hydatidiform moles. J Biochem Mol Toxicol, 30(9):455–461. https://doi.org/10.1002/jbt.21809
Wang JY, Lan J, Zhao JG, et al., 2012. Molecular characterization, polymorphism and association of porcine SPATA19 gene. Mol Biol Rep, 39(10):9741–9746. https://doi.org/10.1007/s11033-012-1839-x
Wang XY, 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. Anim Genet, 48(6):735–736. https://doi.org/10.1111/age.12617
Wang XY, Yang Q, Wang K, et al., 2019. Two strongly linked single nucleotide polymorphisms (Q320P and V397I) in GDF9 gene are associated with litter size in cashmere goats. Theriogenology, 125:115–121. https://doi.org/10.1016/j.theriogenology.2018.10.013
Wang Z, Zhang X, Jiang E, et al., 2020. InDels within caprine IGF2BP1 intron 2 and the 3′-untranslated regions are associated with goat growth traits. Anim Genet, 51(1):117–121. https://doi.org/10.1111/age.12871
Wu H, Pan Y, Zhang QF, et al., 2019. Insertion/deletion (InDel) variations in sheep PLAG1 gene locating in growth-related major QTL are associated with adult body weight and morphometric traits. Small Ruminant Res, 178:63–69. https://doi.org/10.1016/j.smallrumres.2019.08.003
Yin H, Du X, Li QQ, et al., 2019. Variants in BMP7 and BMP15 3′-UTRs associated with reproductive traits in a Large White pig population. Animals (Basel), 9(11):905. https://doi.org/10.3390/ani9110905
Yong Y, He L, 2005. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res, 15(2):97–98. https://doi.org/10.1038/sj.cr.7290272
Zhao Y, Ma YS, Fang Y, et al., 2012. IGF2BP2 genetic variation and type 2 diabetes: a global meta-analysis. DNA Cell Biol, 31(5):713–720. https://doi.org/10.1089/dna.2011.1400
Zheng WM, Grafer CM, Kim J, et al., 2015. Gonadotropin-releasing hormone and gonadal steroids regulate transcription factor mRNA expression in primary pituitary and immortalized gonadotrope cells. Reprod Sci, 22(3): 285–299. https://doi.org/10.1177/1933719114565031
This study was supported by the National Natural Science Foundation of China (Nos. 32060734 and 31760650).
Dongyun XIN, Yangyang BAI, Yi BI, Libang HE, Yuxin KANG, Chuanying PAN, Haijing ZHU, Hong CHEN, Lei QU, and Xianyong LAN declare that they have no conflict of interest.
The animal participants involved in this experiment were maintained in strict accordance with the “Regulations on the Management of Experimental Animal Affairs” (Ministry of Science and Technology of China, 2004) and this study was approved by the International Animal Care and Use Committee (IACUC) of Northwest A&F University, Yangling, China (Protocol No. NWAFAC1008).
About this article
Cite this article
Xin, D., Bai, Y., Bi, Y. et al. Insertion/deletion variants within the IGF2BP2 gene identified in reported genome-wide selective sweep analysis reveal a correlation with goat litter size. J. Zhejiang Univ. Sci. B 22, 757–766 (2021). https://doi.org/10.1631/jzus.B2100079
- Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
- Litter size
- Marker-assisted selection (MAS)