Collective Genetic Interaction Effects and the Role of Antigen Presenting Cells in Autoimmune Diseases
Biotechnology High Performance Computing Software Applications Institute Frederick United States
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Autoimmune diseases occur when immune cells fail to develop or lose their tolerance toward self and destroy bodys own tissues. Both insufficient negative selection of self-reactiveT cells and impaired development of regulatory T cells preventing effector cell activation are believed to contribute to autoimmunity. Genetic predispositions center around the major histocompatibility complex MHC class II loci involved in antigen presentation, the keydeterminant of CD4 T cell activation. Recent studies suggested that variants in the MHCregion also exhibit significant non-additive interaction effects. However, collective interactions involving large numbers of single nucleotide polymorphisms SNPs contributing to such effects are yet to be characterized. In addition, relatively little is known about the celltype-specificity of such interactions in the context of cellular pathways. Here, we analyzed type 1 diabetes T1D and rheumatoid arthritis RA genome-wide association data sets vialarge-scale, high-performance computations and inferred collective interaction effects involving MHC SNPs using the discrete discriminant analysis.
- Medicine and Medical Research