鸡胰岛素样生长因子2基因(IGF2)外显子区功能性SNP预测与分析

doi:10.11843/j.issn.0366-6964.2020.11.006

摘要/Abstract

摘要： 旨在采用生物信息学方法筛选鸡IGF2基因中具有潜在生物学功能的非同义单核苷酸多态性（non-synonymous single nucleotide polymorphisms，nsSNPs）位点，为开展标记辅助选择改良鸡重要经济性状提供理论参考。本研究从dbSNP数据库中检索出鸡IGF2基因的12个nsSNPs位点，利用生物信息学软件SIFT、Polyphen-2、PhD-SNP和SNAP预测其中可能的功能性SNP；使用I-Mutant3.0和Mupro方法对突变位点的氨基酸稳定性进行分析；对鸡IGF2基因编码的氨基酸序列进行多序列比对和进化位点保守性预测，并结合MutPred2预测突变可能造成的功能后果；最后使用Sopma预测IGF2野生型和突变型的蛋白质二级结构，运用I-TASSER构建它们的蛋白质三级结构。结果发现，rs740391349（E29G）、rs735633122（T30P）、rs739078786（L31P）、rs736255842（E35G）及rs736800980（V37G）这5个nsSNPs可能影响鸡IGF2的蛋白功能，且所有位点突变都会使IGF2蛋白稳定性降低。多序列比对及保守性分析显示，rs740391349（E29G）、rs735633122（T30P）和rs736255842（E35G）为高度保守并暴露的功能性残基，MutPred2与二级结构分析结果表明，rs735633122（T30P）和rs736255842（E35G）这两个位点上的突变都导致了α螺旋百分比下降。三级结构分析表明，rs735633122（T30P）和rs736255842（E35G）这2个nsSNPs均会导致IGF2的蛋白空间结构发生变化。综上所述，T30P和E35G位点突变严重影响鸡IGF2蛋白质的结构，可能是影响鸡生长和体组成性状的重要功能性SNPs。

关键词: 鸡, IGF2基因, SNP功能预测, 生物信息学

Abstract: The aim of this study was to use bioinformatics methods to screen non-synonymous single nucleotide polymorphisms (nsSNPs) sites with potential biological functions in chicken IGF2 gene and provide a theoretical basis for carrying out marker-assisted selection to improve important economic traits of chicken. Twelve nsSNPs sites of chicken IGF2 gene were retrieved from dbSNP database. SIFT, Polyphen-2, PhD-SNP, and SNAP were used to predict the possible functional SNPs. The amino acid stability of mutation sites was analyzed by I-Mutant3.0 and Mupro methods. Multiple sequence alignment and conserved prediction of evolutionary sites were carried out on the amino acid sequence encoded by chicken IGF2 gene, and combined with MutPred2 to predict the possible functional consequences caused by mutations. Finally, Sopma was used to predict the secondary structure of IGF2 wild-type and mutant proteins, and I-TASSER was used to construct their tertiary structure. The results showed that rs740391349 (E29G), rs735633122 (T30P), rs739078786 (L31P), rs736255842 (E35G) and rs736800980 (V37G) might affect the protein function of chicken IGF2, and all the mutations reduced the protein stability of IGF2. Multiple sequence alignment and conservative analysis showed that rs740391349 (E29G), rs735633122 (T30P), and rs736255842 (E35G) were highly conserved and exposed functional residues. MutPred2 and secondary structural analysis showed that mutations at rs735633122 (T30P) and rs736255842 (E35G) both led to a decreased percentage of α-helix. Tertiary structural analysis showed that rs735633122 (T30P) and rs736255842 (E35G) could change the spatial structure of IGF2 protein. In summary, mutations at T30P and E35G seriously affect the structure of chicken IGF2 protein and may be the significant functional SNPs affecting chicken growth and body composition traits.

Key words: chicken, IGF2 gene, SNP function prediction, bioinformatics

中图分类号:

S831.2

李玉冬, 王伟佳, 李紫薇, 李瑞楚, 张长超, 王宁, 李辉, 王守志. 鸡胰岛素样生长因子2基因(IGF2)外显子区功能性SNP预测与分析[J]. 畜牧兽医学报, 2020, 51(11): 2665-2678.

LI Yudong, WANG Weijia, LI Ziwei, LI Ruichu, ZHANG Changchao, WANG Ning, LI Hui, WANG Shouzhi. Prediction and Analysis of Functional SNP on Exon Region of Insulin-like Growth Factor 2 Gene (IGF2) in Chickens[J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(11): 2665-2678.

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