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A theory of aging holds that senescence is caused by a dysregulated nuclear factor kappa B (NF-κB) signal transduction network (STN). We adopted a systems genetics approach in our study of the NF-κB STN. Ingenuity Pathways Analysis (IPA) was used to identify gene/gene product interactions between NF-κB and the genes in our transcriptional profiling array. Principal components factor analysis (PCFA) was performed on a sub-network of 19 genes, including two initiators of the toll-like receptor (TLR) pathway, myeloid differentiation primary response gene (88) (MyD88) and TIR (Toll/interleukin-1 receptor)- domain-containing adapter-inducing interferon-β (TRIF). TLR pathways are either MyD88-dependent or TRIF-dependent. Therefore, we also performed PCFA on a subset excluding the MyD88 transcript, and on another subset excluding two TRIF transcripts. Using linkage analysis we found that each set gave rise to at least one factor with a logarithm of the odds (LOD) score greater than 3, two on chromosome 15 at 15q12 and 15q22.2, and another two on chromosome 17 at 17p13.3 and 17q25.3. We also found several suggestive signals (2 < LOD score < 3) at 1q32.1, 1q41, 2q34, 3q23, and 7p15.3. We are currently examining potential associations with single nucleotide polymorphisms within the 1-LOD intervals of our linkage signals.

Item Type:	Refereed Article
Keywords:	nuclear factor kappa B, gene expression network, principal components factor analysis, linkage analysis, systems genetics
Research Division:	Mathematical Sciences
Research Group:	Statistics
Research Field:	Biostatistics
Objective Division:	Health
Objective Group:	Specific Population Health (excl. Indigenous Health)
Objective Field:	Health Related to Ageing
UTAS Author:	Charlesworth, J (Dr Jac Charlesworth)
ID Code:	77521
Year Published:	2012
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2012-04-24
Last Modified:	2017-11-06
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