Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging

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...

Full description

Bibliographic Details
Main Authors: Diego, V., Curran, J., Charlesworth, J., Peralta, J., Voruganti, V., Cole, S., Dyer, T., Johnson, M., Moses, Eric, Göring, H., Williams, J., Comuzzie, A., Almasy, L., Blangero, J., Williams-Blangero, S.
Format: Journal Article
Published: 2012
Online Access:http://hdl.handle.net/20.500.11937/33281
_version_ 1848753901698809856
author Diego, V.
Curran, J.
Charlesworth, J.
Peralta, J.
Voruganti, V.
Cole, S.
Dyer, T.
Johnson, M.
Moses, Eric
Göring, H.
Williams, J.
Comuzzie, A.
Almasy, L.
Blangero, J.
Williams-Blangero, S.
author_facet Diego, V.
Curran, J.
Charlesworth, J.
Peralta, J.
Voruganti, V.
Cole, S.
Dyer, T.
Johnson, M.
Moses, Eric
Göring, H.
Williams, J.
Comuzzie, A.
Almasy, L.
Blangero, J.
Williams-Blangero, S.
author_sort Diego, V.
building Curtin Institutional Repository
collection Online Access
description 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.
first_indexed 2025-11-14T08:31:53Z
format Journal Article
id curtin-20.500.11937-33281
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T08:31:53Z
publishDate 2012
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-332812018-03-29T09:08:50Z Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging Diego, V. Curran, J. Charlesworth, J. Peralta, J. Voruganti, V. Cole, S. Dyer, T. Johnson, M. Moses, Eric Göring, H. Williams, J. Comuzzie, A. Almasy, L. Blangero, J. Williams-Blangero, S. 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/33281 10.1016/j.mad.2011.11.007 restricted
spellingShingle Diego, V.
Curran, J.
Charlesworth, J.
Peralta, J.
Voruganti, V.
Cole, S.
Dyer, T.
Johnson, M.
Moses, Eric
Göring, H.
Williams, J.
Comuzzie, A.
Almasy, L.
Blangero, J.
Williams-Blangero, S.
Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging
title Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging
title_full Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging
title_fullStr Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging
title_full_unstemmed Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging
title_short Systems genetics of the nuclear factor-?B signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging
title_sort systems genetics of the nuclear factor-?b signal transduction network. i. detection of several quantitative trait loci potentially relevant to aging
url http://hdl.handle.net/20.500.11937/33281