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| Status |
Public on Jul 01, 2014 |
| Title |
Analysis of whole-genome copy-number variation in Crohn's disease fistula tissue |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by high throughput sequencing
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| Summary |
Background: Crohn’s disease is presently an incurable inflammatory bowel disease. Fistulae are extensions of the intestinal tract that may form connections with other organs. These are a common complication of Crohn’s disease affecting up to 50% of patients with the most common including perianal and rectovaginal fistulae. The dysregulated growth observed in fistulae shares several major characteristics seen in the development of tumours. These similarities include epithelial-to-mesenchymal transition (EMT), invasive cell growth, increased extracellular matrix production and remodelling, up-regulated local expression of growth factors such as IGF-1 and the down-regulation of apoptosis pathways. Although several susceptibility loci have been described within Crohn’s disease there is no individual gene or mutation that identifies susceptibility or the subsequent formation of fistulae within all people. Copy-number variation (CNV) is one mechanism that may explain much of this genetic complexity. CNV may be caused by a variety of mechanisms such as cycles of chromosomal breakage/fusion/bridging that are typical within chronically inflamed tissue. Interestingly CNV shows locus-specific mutation rates between individuals higher than that of SNPs and has been associated with complex Mendelian traits including disease susceptibility. In this current study we performed array comparative genomic hybridisation (aCGH) analysis of active fistulae resected from patients as part of a previous surgical intervention. As the control for comparison we employed tissue taken from the same patient within the same surgery at an uninvolved site of the gastrointestinal tract. This matched control was employed to better investigate CNV specific to the fistula tissue of each individual avoiding complications associated with the large number of CNV present within the healthy population.
Major question addressed by the work: What are the differences in genetic copy-number within localised intestinal fistula tissue of individuals with Crohn’s disease compared to healthy intestinal tissue from the same individual?
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| Overall design |
Samples were selected from patients presenting with Crohn’s Disease fistulae at Eastern Health Department of Gastroenterology and Hepatology (Arnold Street, Box Hill, Victoria, Australia). The 8 samples used in this study were formalin-fixed paraffin-embedded (FFPE) specimens following a surgical intervention to remove fistula tissue. To focus on changes within the individual patient we used tissue taken from the same surgery at an uninvolved region of the intestine as the matched control for CNV analysis.
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| Contributor(s) |
Parker PD, van Langenberg D, Hosking P, Russell A |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Feb 12, 2013 |
| Last update date |
Jul 02, 2014 |
| Contact name |
phillip david parker |
| Organization name |
Deakin University
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| Department |
Health
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| Lab |
CPAN
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| Street address |
221 Burwood Highway
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| City |
Burwood |
| State/province |
Victoria |
| ZIP/Postal code |
3125 |
| Country |
Australia |
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| Platforms (1) |
| GPL10123 |
Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA189278 |
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