京海黄鸡IL-6基因启动子区多态性的生物信息学分析  

Bioinformatics Analysis of Polymorphism in the Promoter Region of IL-6 Gene in Jinghai Yellow Chickens(Gallus gallus)

作　　者：辛世杰[1,2] 安婷婷 戴国俊[1,2] 张菁菁 王诗琴[1,2] 王晓慧 张跟喜[1,2] 谢凯舟 王金玉[1,2] 

机构地区：[1]扬州大学动物科学与技术学院,扬州225009 [2]扬州大学江苏省动物遗传育种与分子设计重点实验室,扬州225009

出　　处：《农业生物技术学报》2018年第1期113-122,共10页Journal of Agricultural Biotechnology

基　　金："十二五"国家科技支撑计划项目(No.2014BAD13B02);江苏现代农业(肉鸡)产业技术体系(No.SXGC[2017]298);国家现代农业产业技术体系专项资金(No.CARS-41);江苏省高校优势学科建设工程项目(No.PAPD)

摘　　要：前炎性细胞因子白细胞介素6(interleukin-6,IL-6)在许多慢性炎症和自身免疫性疾病的发病机制中起着至关重要的作用,尤其是炎症性肠病。为了从分子水平上探讨IL-6基因的表达调控,本研究以京海黄鸡(Gallus gallus)为素材,通过基因组DNA测序技术,检测IL-6基因上游-2 200 bp至下游500 bp区域中的单核苷酸多态(single nucleotide polymorphism,SNP),同时运用生物信息学软件预测IL-6基因核心启动子区转录因子以及CpG岛(CpG islands),分析所测SNPs以及该基因启动子区SNP突变前后转录因子和CpG岛的变化。测序结果表明,京海黄鸡中共检测到28个SNPs位点,其中位于5'调控区有19个,外显子区2个(均为同义突变),内含子区2个,3'区5个;在28个突变位点中,发现有4个为Gen Bank中未标注的SNPs,其中3个(G-357 A、C-447 G和A-663 G)位于5'调控区,1个位于3'区(C3177T)。生物信息学分析表明,有11个SNPs位于IL-6基因核心启动子区,并导致转录因子发生了改变;同时由于启动子区C-939G的突变,导致CpG岛区域由原来的3个变为2个,由此推测上述SNPs可能通过影响IL-6基因的启动子区转录因子以及甲基化区域的改变影响IL-6基因的表达调控。研究结果对进一步探讨IL-6基因的功能和作用,以及这些SNPs与鸡肠道炎症的抗性及生产性能的关系具有十分重要的意义。Interleukin-6 （IL-6） is also called proinflammatory cytokine interleukin-6, plays a critical role in many chronic inflammatory and autoimmune diseases, especially inflammatory bowel disease. In this study, in order to investigate the regulation of IL-6 gene expression at the molecular level, Jinghai Yellow Chickens（Gallus gallus） were used as experimental materials, genomic DNA sequencing was used to detect single nucleotide polymorphisms （SNPs） of proinflammatory cytokine IL-6 gene from the upstream -2 200 bp to downstream 500 bp region, bioinformatics softwares were used to predict the core promoter region transcription factors and CpG islands of IL-6 gene, to analyze how the single nucleotide mutation of IL-6 gene changed the transcription factors and the CpG islands. The sequencing results showed that 28 SNPs sites were found in the gene, nineteen SNPs were located in the 5＇ regulatory region, two were located in exon （both of them are synonymous mutation）, two were located in intron and 5 SNPs were located in the 3＇ region. Out of 28 mutation sites, there were 4 SNPs are not labeled in GenBank, three of them （G -357 A, C -447 G and A -663 G） were located in the 5＇ regulatory region and one in the 3＇ region （C3177T）. Bioinformatics analysis showed that IL-6 gene had a very distinct core promoter recognition feature, there were 11 SNPs located in this core region, causing the change of transcription factor binding sites, the new discovered G-357A mutation may generate a new transcription factor binding site （Sp1） from the beginning of -360 bp, C-447G mutation can lead to one transcription factor change （HB become C/E BPalp）, A-663G mutation may lead to the formation of 3 new transcription factor binding sites （AP-2alph and two Sp1）, other detected SNPs could produce 5 new transcription factor binding sites （Sp1, ISGF-3, TEC1, IRF-1, ICS BP） and lead to 7 transcription factor binding sites （MEB-1, GLO, GATA-1, C/E BPal, Sp1, GR, Sp1） disappearing; meanwhile, t

关 键 词：京海黄鸡 白介素6基因(IL-6) SNPS 转录因子 CPG岛 生物信息学 

分 类 号：S831.2[农业科学—畜牧学]