论文

家兔ATG16L1基因多态性与非特异性消化道紊乱易感性的研究

  • 肖正龙 ,
  • 张龚炜 ,
  • 杨宇 ,
  • 王杰 ,
  • 赖松家
展开
  • 四川农业大学动物遗传育种研究所, 四川 成都 611130
肖正龙(1986- ),男,四川宜宾人,在读硕士,主要从事分子遗传育种研究

收稿日期: 2013-05-05

  网络出版日期: 2014-10-14

基金资助

国家现代农业技术体系项目(CARS-44-A-2);四川省“十二五”科技支撑项目(2011NZ0099-4)

The Association between the Polymorphism of ATG16L1 and Non- specific Digestive Disorder in Rabbit

  • XIAO Zheng-long ,
  • ZHANG Gong-wei ,
  • YANG Yu ,
  • WANG Jie ,
  • LAI Song-jia
Expand
  • Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu 611130, China

Received date: 2013-05-05

  Online published: 2014-10-14

摘要

为了研究家兔ATG16L1基因对非特异性消化道紊乱的易感性,试验采用PCR-HRM技术,首次对家兔ATG16L1基因进行单核苷酸多态性(SNP)检测,同时结合低纤维群体结肠ATG16L1基因mRNA表达量进行关联分析。结果表明:ATG16L1基因存在1个SNP位点(c.1482 G>A)与NSDD的易感性相关联;c.1482 G>A位点A等位基因能增加NSDD的易感性(OR=1.43,95%置信区间:1.08~1.91,P<0.05);在隐性遗传模型中,AA基因型能增加NSDD的易感性(OR=1.69,95%置信区间:1.05~2.78,P<0.05);ATG16L1基因在结肠中的mRNA表达量随着炎症的加剧显著升高(P<0.05);AA基因型在整个低纤维诱导NSDD组中的表达水平最低(P<0.05)。这些结果均表明,ATG16L1基因与家兔NSDD的遗传易感性相关。

本文引用格式

肖正龙 , 张龚炜 , 杨宇 , 王杰 , 赖松家 . 家兔ATG16L1基因多态性与非特异性消化道紊乱易感性的研究[J]. 华北农学报, 2013 , 28(4) : 234 -238 . DOI: 10.3969/j.issn.1000-7091.2013.04.043

Abstract

To study the susceptibility of ATG16L1 gene to non- specific digestive disorder (NSDD) in rabbit, single nucleotide polymorphism (SNP) of rabbit ATG16L1 gene was firstly detected by PCR- HRM and the associa- tion analysis of ATG16L1 gene mRNA expression in colon of fibre- deficient diet group was conducted.The results found that there was a SNP locus (c. 1482 G > A) in ATG16L1 gene and the SNP locus was associated with the sus- ceptibility to NSDD; the allele A of c. 1482 G > A could increase the susceptibility (OR = 1. 43, 95% confidence interval: 1. 08- 1. 91, P < 0. 05); in recessive genetic model,the genotype AA could increase the susceptibility (OR = 1. 69,95% confidence interval: 1.05- 2.78,P < 0.05); along with the increasing severity of non- specific digestive disorder, the ATG16L1 gene mRNA expression in colon was gradually increased (P < 0.05); genotype AA had the lowest mRNA expression in fibre- deficient diet group (P < 0.05) .These results showed that ATG16L1 gene was associated with the genetic susceptibility to NSDD in rabbit.

参考文献

[1] Garreau H,Eady S J,Hurtaud J,et al. Genetic parameters of production traits and resistance to digestive disorders in a commercial rabbit population[C]. Proc 9th World Rab-bit Congr,June,2008: 10-13.
[2] Ogura Y,Bonen D K,Inohara N,et al. A frameshift muta-tion in NOD2 associated with susceptibility to Crohn' s disease[J]. Nature,2001,411(6837): 603-606.
[3] Hugot J P,Chamaillard M,Zouali H,et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease[J]. Nature,2001,411 (6837 ): 599-603.
[4] Duerr R H,Taylor K D,Brant S R,et al. A genome-wide association study identifies IL23R as an inflammatory bow-el disease gene[J] . Science,2006,314 (5804): 1461-1463.
[5] Cardon L R,Burton P R,Clayton D G,et al. Genome-wide association study of 14 000 cases of seven common disea-ses and 3 000 shared controls[J]. Nature,2007,447(7145): 661-678.
[6] Tremelling M,Cummings F,Fisher S A,et al. IL23R vari-ation determines susceptibility but not disease phenotype in inflammatory bowel disease[J]. Gastroenterology,2007,132(5): 1657-1664.
[7] Peltekova V D,Wintle R F,Rubin L A,et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease[J]. Nature Genetics,2004,36 (5): 471-475.
[8] Rioux J D,Daly M J,Silverberg M S,et al. Genetic varia-tion in the 5q31 cytokine gene cluster confers susceptibili-ty to Crohn disease[J]. Nature Genetics,2001,29 (2): 223-228.
[9] Mathew C G. New links to the pathogenesis of Crohn dis-ease provided by genome-wide association scans[J]. Na-ture Reviews Genetics,2008,9(1): 9-14.
[10] Prescott N J,Fisher S A,Franke A,et al. A nonsynony-mous SNP in ATG16L1 predisposes to ileal Crohn's dis-ease and is independent of CARD15 and IBD5[J]. Gas-troenterology,2007,132(5): 1665-1671.
[11] Rioux J D,Xavier R J,Taylor K D,et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease path-ogenesis[J]. Nature,2007,39: 596-604.
[12] Hampe J,Franke A,Rosenstiel P,et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 [J]. Nature Genetics,2006,39(2): 207-211.
[13] Kuballa P,Huett A,Rioux J D,et al. Impaired autophagy of an intracellular pathogen induced by a Crohn' s dis-ease associated ATG16L1 variant[J]. PLoS One,2008,3 (10): e3391.
[14] Cadwell K,Liu J Y,Brown S L,et al. A key role for auto-phagy and the autophagy gene Atg16l1 in mouse and hu-man intestinal Paneth cells[J]. Nature,2008,456 (7219): 259-263.
[15] Cadwell K,Patel K K,Komatsu M,et al. A common rolefor Atg16L1,Atg5,and Atg7 in small intestinal Paneth cells and Crohn's disease[J]. Autophagy,2009,5(2): 250.
[16] Zhang G W,Wang H Z,Chen S Y,et al. A reduced inci-dence of digestive disorders in rabbits is associated with allelic diversity at the TLR4 locus[J]. Vet Immunol Im-munopathol,2011,144(3-4): 482-486.
[17] Bennegadi N,Gidenne T,Licois D,et al. Impact of fibre deficiency and sanitary status on non-specific enteropa-thy of the growing rabbit[J]. Animal Research,2001,50 (5): 401-414.
[18] Gidenne T,Pinheiro V,Falcao L. A comprehensive ap-proach of the rabbit digestion: consequences of a reduc-tion in dietary fibre supply[J]. Livestock Production Science,2000,64(2-3): 225-237.
[19] Martino A,Mancuso T,Anna M R. Application of High-Resolution Melting to Large-Scale,High-Throughput SNP Genotyping[J]. J Biomol Screen,2010,15 (6): 623-629.
[20] Sol X,Guin E,Valls R,et al. SNPStats: a web tool for the analysis of association studies[J]. Bioinformatics,2006,22(15): 1928-1929.
[21] Vandesompele J,Preter K D,Pattyn F,et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes [J]. Genome Biol,2002,3(7): RESEARCH0034.
[22] Blumberg R S,Saubermann L J,Strober W,et al. Animal models of mucosal inflammation and their relation to hu-man inflammatory bowel disease[J]. Curr Opin Immu-nol,1999,11(6): 648-56.
[23] Lukefahr S D,Cheeke P R,McNitt J I,et al. Limitations of intensive meat rabbit production in North America: A review. Canadian Journal of Animal Science,2004,84 (3): 349-360.
[24] Sauna Z E,Kimchi-Sarfaty C. Understanding the contri-bution of synonymous mutations to human disease[J]. Nat Rev Genet,2011,12(10): 683-691.
文章导航

/