Assembly of inflammation-related genes for pathway-focused genetic analysis

Matthew J. Loza, Charles E. McCall, Liwu Li, William B Isaacs, Jianfeng Xu, Bao Li Chang

Research output: Contribution to journalArticle

Abstract

Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the inganuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP) arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs) and African (21,542 SNPs) populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and associated subpathways can facilitate comprehensive inflammation pathway- focused association analyses.

Original languageEnglish (US)
Article numbere1035
JournalPLoS One
Volume2
Issue number10
DOIs
StatePublished - Oct 17 2007

Fingerprint

genetic techniques and protocols
Genes
inflammation
Inflammation
genes
Single Nucleotide Polymorphism
Disease Susceptibility
single nucleotide polymorphism
disease resistance
immune response
Polymorphism
Genome
Population
gene interaction
genome
Inborn Genetic Diseases
Nucleotides
cells
Association reactions
genotyping

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Assembly of inflammation-related genes for pathway-focused genetic analysis. / Loza, Matthew J.; McCall, Charles E.; Li, Liwu; Isaacs, William B; Xu, Jianfeng; Chang, Bao Li.

In: PLoS One, Vol. 2, No. 10, e1035, 17.10.2007.

Research output: Contribution to journalArticle

Loza, Matthew J. ; McCall, Charles E. ; Li, Liwu ; Isaacs, William B ; Xu, Jianfeng ; Chang, Bao Li. / Assembly of inflammation-related genes for pathway-focused genetic analysis. In: PLoS One. 2007 ; Vol. 2, No. 10.
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