title: Systems genetics of the nuclear factor-κB signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging.
abstract: 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.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245-0549, USA. vdiego@txbiomedgenetics.org
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Diego
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Jac
authors.initials: J
authors.lastname: Charlesworth
authors.forename: Juan M
authors.initials: JM
authors.lastname: Peralta
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.forename: Jeff T
authors.initials: JT
authors.lastname: Williams
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams-Blangero
mesh_terms: D000375:Aging / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics* / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008126:Lod Score; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*; D049490:Systems Biology / Q000379:methods
chemical_list: D016328:NF-kappa B