Micoarray analysis to identify gastritis susceptibility genes on chromosome 4

Jordan, M.A., Biros, E., van Driel, I.R., Ang, K.D., and Baxter, A.G. (2009) Micoarray analysis to identify gastritis susceptibility genes on chromosome 4. In: Proceedings of the 39th Annual Meeting of the Australasian Society for Immunology 2009, pp. 235-236. From: 39th Annual Meeting of the Australasian Society for Immunology 2009, 6-10 December 2009, Gold Coast, QLD, Australia.

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Abstract

Autoimmune chronic (type A) gastritis is an organ-specific inflammatory disease leading to gastric atrophy, vitamin B12 deficiency and pernicious anaemia, and is associated with increased susceptibility to gastric cancer. Thymectomy of BALB/c mice on the third day of life is a well-characterized model of the disease and results in experimental autoimmune gastritis (EAG)in approximately 70% of treated mice. Our previous genetic linkage study of an F2 intercross of the BALB/c susceptible and C57BL/6 resistant strains identified two distinct susceptibility regions on distal chromosome 4 Gasa1 and Gasa2‚. As the overall linkage region spanned ~38Mb , 39 subcongenic lines were established in order to dissect the Gasa1 susceptibility region from that of Gasa 2. Phenotypic analysis of the congenic strains for gastritis susceptibility allowed us to narrow the Gasa1 congenic region to between rs27480233 and rs27528755 (~9.5Mb) and the Gasa2 region to between D4mit343 and the distal end of the chromosome (~14Mb). In order to identify a subset of candidate genes within the Gasa2 linkage interval, microarray gene expression analysis using Affymetrix Mouse 430 series 2 expression microarrays was performed on thymi of 4 week old disease-protected BALB.B6-GasaA and disease-prone BALB.B6931-343‚ mice (n=7/group). Applying a Mann Whitney U-test with a stringent statistical threshold such that there was no overlap in signals between the two groups, a total of 94 genes were identified as being highly differentially expressed (i.e. those with a p<0.03), of which 8 mapped to the Gasa2 congenic region (~0.5% of genome; x2 =118.6; df = 1; p < 10^-27 ; x2 one sample test). So far three of the genes have been validated by real time PCR on a new sample set.   

Item ID: 8452
Item Type: Conference Item (Abstract / Summary)
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Date Deposited: 31 May 2010 03:28
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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