Detection and preliminary screening of the human gene expression profile for Hirschsprung's disease

Wang,Xin; Wang,Shiqi; Jin,Xianqing; Wang,Ning; Luo,Yuanyuan; Teng,Yinping

doi:10.3892/mmr.2015.4633

Detection and preliminary screening of the human gene expression profile for Hirschsprung's disease

Authors:
- Xin Wang
- Shiqi Wang
- Xianqing Jin
- Ning Wang
- Yuanyuan Luo
- Yinping Teng
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Affiliations: Tumour Laboratory of Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China
Published online on: December 1, 2015 https://doi.org/10.3892/mmr.2015.4633
Pages: 641-650
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated a genome microarray of colorectal lesions (spasm segments) in children with Hirschsprung's disease (HSCR), and analyzed the results. In addition, the present study screened for differentially expressed genes in children with HSCR. Microarray technology was used to examine the human gene expression profiles of the colorectal lesions (spasm segments) of six children with HSCR, and three normal colon tissue samples. The data were analyzed be determining P‑values of significance and absolute fold changes. Preliminary screening was performed to identify genes exhibiting significant differential expression in children with HSCR, and these target genes were analyzed in subsequent verification and analytical investigations. Of >20,000 detected human genes, the preliminary screenings demonstrated that 3,850 genes were differentially expressed and upregulated, with P<0.05 and >2‑fold absolute changes in expression. In addition, 645 differentially expressed genes with P<0.05 and >2‑fold absolute changes were downregulated. Of the upregulated genes, 118 were involved in classic signaling pathways, compared with 11 of the downregulated genes (P<0.001; absolute fold change >2‑fold). HSCR etiology is complex and often involves multiple gene changes. Microarray technology can produce large quantities of gene expression data simultaneously, and analyzing this data using various techniques may provide a fast and efficient method for identifying novel gene targets and for investigating the mechanisms underlying HSCR pathogenesis.

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1	Theveneau E and Mayor R; Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration. Dev Biol. 2012 Jun 1;366(1): 34–54. View Article : Google Scholar : PubMed/NCBI
2	Goldberg EL: An epidemiological study of Hirschsprung's disease. Int J Epidemiol. 13:479–485. 1984. View Article : Google Scholar : PubMed/NCBI
3	Parisi MA and Kapur RP: Genetics of Hirschsprung disease. Curr Opin Pediatr. 12:610–617. 2000. View Article : Google Scholar : PubMed/NCBI
4	White Jacqueline K, Gerdin Anna-Karin, Karp Natasha A, et al: Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes. Cell. 2013 July 18;154(2): 452–464. View Article : Google Scholar : PubMed/NCBI
5	Washita T, Kruger GM, Pardal R, Kiel MJ and Morrison SJ: Hirsch–sprung disease is linked to defecta in neural crest cell function. Science. 2003.301(5635): 972–976. View Article : Google Scholar
6	Erin Mundt, Michael D and Bate: Genetics of Hirschsprung disease and anorectal malformations. Seminars in Pediatric Surgery. 2010.19:107–117. View Article : Google Scholar
7	Angrist M, Bolk S, Halushka M, Lapchak PA and Chakravarti A: Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. Nat Genet. 14:341–344. 1996. View Article : Google Scholar : PubMed/NCBI
8	Salomon R, Attié T, Pelet A, Bidaud C, Eng C, Amiel J, Sarnacki S, Goulet O, Ricour C, Nihoul-Fékété C, et al: Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease. Nat Genet. 14:345–347. 1996. View Article : Google Scholar : PubMed/NCBI
9	Bolk S, Pelet A, Hofstra RM, Angrist M, Salomon R, Croaker D, Buys CH, Lyonnet S and Chakravarti A: A human model for multigenic inheritance: Phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus. Proc Natl Acad Sci USA. 97:268–273. 2000. View Article : Google Scholar : PubMed/NCBI
10	Nishiyama C, Uesaka T, Manabe T, Yonekura Y, Nagasawa T, Newgreen DF, Young HM and Enomoto H: Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system. Nat Neurosci. 15:1211–1218. 2012. View Article : Google Scholar : PubMed/NCBI
11	Passarge E: The genetics of Hirschsprung's disease. Evidence for heterogeneous etiology and a study of sixty-three families. N Engl J Med. 276:138–143. 1967. View Article : Google Scholar : PubMed/NCBI
12	Spouge D and Baird PA: Hirschsprung disease in a large birth cohort. Teratology. 32:171–177. 1985. View Article : Google Scholar : PubMed/NCBI
13	Kerstjens-Frederikse WS, Hofstra RM, van Essen AJ, Meijers JH and Buys CH: A Hirschsprung disease locus at 22q11? J Med Genet. 36:221–224. 1999.PubMed/NCBI
14	Ryan ET, Ecker JL, Christakis NA and Folkman J: Hirschsprung's disease: Associated abnormalities and demography. J Pediatr Surg. 27:76–81. 1992. View Article : Google Scholar : PubMed/NCBI
15	Badner JA, Sieber WK, Garver KL and Chakravarti A: A genetic study of Hirschsprung disease. Am J Hum Genet. 46:568–580. 1990.PubMed/NCBI
16	Sarioglu A, Tanyel FC, Büyükpamukçu N and Hiçsönmez A: Clinical risk factors of Hirschsprung-associated enterocolitis. I: Preoperative enterocolitis. Turk J Pediatr. 39:81–89. 1997.PubMed/NCBI
17	Amiel J and Lyonnet S: Hirschsprung disease, associated syndromes, and genetics: A review. J Med Genet. 38:729–739. 2001. View Article : Google Scholar : PubMed/NCBI
18	Fu M, Lui VC, Sham MH, Cheung AN and Tam PK: HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts. Dev Dyn. 228:1–10. 2003. View Article : Google Scholar : PubMed/NCBI
19	Schena M, Shalon D, Davis RW and Brown PO: Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 270:467–470. 1995. View Article : Google Scholar : PubMed/NCBI
20	Heller RA, Schena M, Chai A, Shalon D, Bedilion T, Gilmore J, Woolley DE and Davis RW: Discovery and analysis of inflammatory disease-related genes using cDNA microarrays. Proc Natl Acad Sci USA. 94:2150–2155. 1997. View Article : Google Scholar : PubMed/NCBI
21	De Risi J, Penland L, Brave PO, et al: Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet. 1996.14(4): 457–460. View Article : Google Scholar
22	Wu TD: Analysing gene expression data from DNA microarrays to identify candidate genes. J Pathol. 195:53–65. 2001. View Article : Google Scholar : PubMed/NCBI
23	Miertus J and Amoroso A: Microarray-based genetics of cardiac malformations. Ital Heart J. 2:565–567. 2001.PubMed/NCBI
24	Bassett DE Jr, Eisen M and Boguski MS: Gene expression informatics it's all in your mind. Nat Genet. 1999.21(Suppl 1): 51–55. View Article : Google Scholar : PubMed/NCBI
25	Tomac AC, Grinberg A, Huang SP, Nosrat C, Wang Y, Borlongan C, Lin SZ, Chiang YH, Olson L, Westphal H and Hoffer BJ: Glial cell line-derived neurotrophic factor receptor alpha1 availability regulates glial cell line-derived neurotrophic factor signaling: Evidence from mice carrying one or two mutated alleles. Neuroscience. 95:1011–1023. 2000. View Article : Google Scholar : PubMed/NCBI
26	Barlow A, de Graaff E and Pachnis V: Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron. 40:905–916. 2003. View Article : Google Scholar : PubMed/NCBI
27	Druckenbrod NR and Epstein ML: Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors. Development. 136:3195–3203. 2009. View Article : Google Scholar : PubMed/NCBI
28	Lee HO, Levorse JM and Shin MK: The endothelin receptor-B is required for the migration of neural crest-derived melanocyte and enteric neuron precursors. Dev Biol. 259:162–175. 2003. View Article : Google Scholar : PubMed/NCBI
29	Ro S, Hwang SJ, Muto M, Jewett WK and Spencer NJ: Anatomic modifications in the enteric nervous system of piebald mice and physiological consequences to colonic motor activity. Am J Physiol Gastrointest Liver Physiol. 290:G710–G718. 2006. View Article : Google Scholar
30	Goldstein AM, Brewer KC, Doyle AM, Nagy N and Roberts DJ: BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system. Mech Dev. 122:821–833. 2005. View Article : Google Scholar : PubMed/NCBI
31	Faure C, Chalazonitis A, Rhéaume C, Bouchard G, Sampathkumar SG, Yarema KJ and Gershon MD: Gangliogenesis in the enteric nervous system: Roles of the polysialylation of the neural cell adhesion molecule and its regulation by bone morphogenetic protein-4. Dev Dyn. 236:44–59. 2007. View Article : Google Scholar
32	Ramalho-Santos M, Melton DA and McMahon AP: Hedgehog signals regulate multiple aspects of gastrointestinal development. Development. 127:2763–2772. 2000.PubMed/NCBI
33	Fu M, Lui VC, Sham MH, Pachnis V and Tam PK: Sonic hedgehog regulates the proliferation, differentiation and migration of enteric neural crest cells in gut. J Cell Biol. 166:673–684. 2004. View Article : Google Scholar : PubMed/NCBI
34	Ding X, Zhao Z, Duan W, Wang S and Jin X, Xiang L and Jin X: Expression patterns of CXCR4 in different colon tissue segments of patients with Hirschsprung's disease. Exp Mol Pathol. 95:111–116. 2013. View Article : Google Scholar : PubMed/NCBI
35	Choudhry Z, Rikani AA, Choudhry AM, Tariq S, Zakaria F, Asghar MW, Sarfraz MK, Haider K, Shafiq AA and Mobassarah NJ: Sonic hedgehog signalling pathway: A complex network. Ann Neurosci. 21:28–31. 2014. View Article : Google Scholar : PubMed/NCBI
36	Ngan ES, Garcia-Barceló MM, Yip BH, Poon HC, Lau ST, Kwok CK, Sat E, Sham MH, Wong KK and Wainwright BJ: Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans. J Clin Invest. 121:3467–3478. 2011. View Article : Google Scholar : PubMed/NCBI
37	Clark CC, Cohen I, Eichstetter I, Cannizzaro LA, McPherson JD, Wasmuth JJ and Iozzo RV: Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21. Genomics. 18:249–260. 1993. View Article : Google Scholar : PubMed/NCBI
38	Bhatt PM and Malgor R: Wnt5a: A player in the pathogenesis of atherosclerosis and other inflammatory disorders. Atherosclerosis. 237:155–162. 2014. View Article : Google Scholar : PubMed/NCBI