Gene-Gene Interactions in Immunology as Exemplified by Studies on Autoantibodies against 60 kDa Heat-shock Protein

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The relationship between genotype and phenotype is expected to be nonlinear for most common, multifactorial human diseases, such as cancer, cardiovascular disease and systemic autoimmune diseases. The genomic research using high-throughput technology to generate genetic data on population level grows more rapid than the methods to analyse those data. The interpretation of vast quantities of genotype-phenotype information is even more complicated if one has the intention to explore effects of gene-gene or gene-environment interactios. The aim of this chapter is to summarize the basic features of gene-gene interactions (also called epistasis) together with appropriate strategies and methods to detect it. Epistasis is defined in its biological sense as interaction between two or more DNA variations either directly or indirectly, to alter disease risk separate from their independent effects. Epistasis is commonly found when properly investigated. However, taking multiple interactions into account, epistasis is difficult to detect and charaterize using traditional parametric methods such as logistic and linear regression because of the sparseness of the data in high dimensions. An example will be presented of how gene-gene interaction effects contribute to the determination of natural autoantibody levels, and thus possibly to risk of systemic autoimmune diseases. The success of our study to identify gene-gene interaction effects in association with autoantibody concentration was based on prior knowledge. However, owing to recent technological developments, researchers must face an incredible large amount of results and fast growing databases, which does not allow the testing of all prior hypotheses in a reasonable time with standard methods. Therefore, new methods are being developed and applied, such as the multifactor dimensionality reduction method or logical analysis of data. These approaches are, besides finding the 'main effects', also suitable for analysis of interaction effects.

Original languageEnglish
Title of host publicationImmunogenomics and Human Disease
PublisherJohn Wiley & Sons, Ltd
Pages351-370
Number of pages20
ISBN (Print)9780470015308
DOIs
Publication statusPublished - May 16 2006

Fingerprint

Immunology
Chaperonin 60
Heat-Shock Proteins
Allergy and Immunology
Autoantibodies
Genes
Autoimmune Diseases
Multifactor Dimensionality Reduction
Genotype
Phenotype
Linear regression
Logistics
Linear Models
Cardiovascular Diseases
Logistic Models
Research Personnel
Throughput
Association reactions
Databases
Technology

Keywords

  • Cellular stress response
  • Gene-gene interaction
  • Genetic linkage
  • Heat-inducible genes
  • Heat-shock proteins
  • Logistic regression models
  • Molecular chaperones
  • Pattern recognition
  • Variance components method

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gene-Gene Interactions in Immunology as Exemplified by Studies on Autoantibodies against 60 kDa Heat-shock Protein. / Prohászka, Z.

Immunogenomics and Human Disease. John Wiley & Sons, Ltd, 2006. p. 351-370.

Research output: Chapter in Book/Report/Conference proceedingChapter

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