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2010
Journal Article
Titel
Differential allelic expression of genes associated with asthma
Titel Supplements
Abstract
Abstract
An important question in ongoing research of genetic traits in complex diseases is functional relevance of identified disease associating genetic factors. previous termDifferential allelic expressionnext term (DAE) has been estimated to affect 20-50% of human previous termgenesnext term and can be measured by genotyping cSNPs in heterozygous cDNA samples. Coding SNPs in IL13 and CSF2 were associated with asthma. We investigated whether those cSNPs are correlated with cis-directed previous termexpressionnext term of a specific allele. Results may provide a functional link between specific genetic variants and specific pathological mechanism related to asthma. One coding SNP per previous termgenenext term was investigated. About 50 immortalized B cell-lines were screened for heterozygosity. Genomic DNA (gDNA), RNA and cDNA were won. To identify DAE, a mass-based genotyping system was used for quantitative genotyping of both alleles. Significant derivation of previous termallelicnext term ratios between cDNA and gDNA samples indicated previous termallelicnext term regulation. Similar direction of intra-sample effects for a given SNP indicated cis-regulation. Both SNPs showed significant DAE (P[IL13] = 0.002, P[CSF2] = 0.01). For IL13, average previous termexpressionnext term of the A allele was about 22% above the previous termexpressionnext term of the major G allele. For CSF2, the T allele was expressed about 38% more than the C allele. We could detect cis-directed DAE in previous termgenesnext term associated with asthma. For IL13, higher previous termexpressionnext term in the presence of allele A might contribute to the known increase of functional activity of the isoform. For CSF2 the allele T previously showed a genetic risk of susceptibility to asthma. This allele was significantly higher expressed than the other. It might be speculated that genetically entailed elevated CSF2 previous termexpressionnext term promotes macrophage and neutrophil function during inflammatory reactions which is linked to increased inflammatory events in asthma. Overall, analysis of DAE of disease-associated markers proves an efficient approach for elucidating functional and possibly pathological relevance of SNPs.