Assembly of Inflammation-Related Genes for Pathway-Focused Genetic Analysis
Open Access
- 17 October 2007
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 2 (10), e1035
- https://doi.org/10.1371/journal.pone.0001035
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 Ingenuity 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.Keywords
This publication has 52 references indexed in Scilit:
- Tag SNP selection for candidate gene association studies using HapMap and gene resequencing dataEuropean Journal of Human Genetics, 2007
- TNF polymorphisms and risk of psoriatic arthritisAnnals Of The Rheumatic Diseases, 2005
- Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosisArthritis & Rheumatism, 2002
- New Mutations of CIAS1 That Are Responsible for Muckle-Wells Syndrome and Familial Cold Urticaria: A Novel Mutation Underlies Both SyndromesAmerican Journal of Human Genetics, 2002
- NF-κB in cancer: from innocent bystander to major culpritNature Reviews Cancer, 2002
- Chronic inflammation and cancer.2002
- Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndromeNature Genetics, 2001
- The spectrum of Familial Mediterranean Fever (FMF) mutationsEuropean Journal of Human Genetics, 2001
- The Disease Spectrum ofHelicobacter Pylori: The Immunopathogenesis of Gastroduodenal Ulcer and Gastric CancerAnnual Review of Microbiology, 2000
- Infections as a major preventable cause of human cancerJournal of Internal Medicine, 2000