Aldons J. Lusis

Mapping the Genetic Architecture of Gene Expression in Human Liver (2008)

Eric E. Schadt, Cliona Molony, Eugene Chudin, Ke Hao, Xia Yang, Pek Y. Lum, ...

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order...

Using genetic markers to orient the edges in quantitative trait networks: The NEO software (2008)

Aten, Jason E, Fuller, Tova F, Lusis, Aldons J, Horvath, Steve

Abstract Background Systems genetic studies have been used to identify genetic loci that affect transcript abundances and clinical traits such as body weight. The pairwise correlations between gene...

Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells (2007)

Gong, Ke, Zhao, Wei, Li, Ning, Barajas, Berenice, Kleinman, Michael, Sioutas, Constantinos, ...

Abstract Background Ambient air pollution is associated with increased cardiovascular morbidity and mortality. We have found that exposure to ambient ultrafine particulate matter, highly enriched in...

Dosage compensation is less effective in birds than in mammals (2007)

Itoh, Yuichiro, Melamed, Esther, Yang, Xia, Kampf, Kathy, Wang, Susanna, Yehya, Nadir, ...

Abstract Background In animals with heteromorphic sex chromosomes, dosage compensation of sex-chromosome genes is thought to be critical for species survival. Diverse molecular mechanisms have...

Integrating Genetic and Network Analysis to Characterize Genes Related to Mouse Weight (2006)

Anatole Ghazalpour, Sudheer Doss, Bin Zhang, Susanna Wang, Christopher Plaisier, Ruth Castellanos, ...

Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker...

Integrating Genetic and Network Analysis to Characterize Genes Related to Mouse Weight (2006)

Anatole Ghazalpour, Sudheer Doss, Bin Zhang, Susanna Wang, Christopher Plaisier, Ruth Castellanos, ...

Gene mapping approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. Recently, several groups have proposed...

Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity (2006)

Susanna Wang, Nadir Yehya, Eric E. Schadt, Hui Wang, Thomas A. Drake, Aldons J. Lusis

The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological...

Genomic analysis of metabolic pathway gene expression in mice (2005)

Ghazalpour, Anatole, Doss, Sudheer, Sheth, Sonal S, Ingram-Drake, Leslie A, Schadt, Eric E, Lusis, Aldons J, ...

Abstract Background A segregating population of (C57BL/6J × DBA/2J)F2 intercross mice was studied for obesity-related traits and for global gene expression in liver. Quantitative trait locus...

Cis-acting expression quantitative trait loci in mice (2005)

Doss, S, Schadt, E E, Drake, T A, Lusis, Aldons J

We previously reported the analysis of genome-wide expression profiles and various diabetes-related traits in a segregating cross between inbred mouse strains C57BL/6J (B6) and DBA/2J (DBA). By...

Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis

Cases, Sylvaine, Smith, Steven J., Zheng, Yao-Wu, Myers, Heather M., Lear, Steven R., Sande, Eric, ...

Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the terminal and only...

Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase

Nathan, Lauren, Shi, Weibin, Dinh, Hillary, Mukherjee, Tapan K., Wang, Xuping, Lusis, Aldons J., ...

The effects of testosterone on early atherogenesis and the role of aromatase, an enzyme that converts testosterone to estrogens, were assessed in low density lipoprotein receptor-deficient male mice...

Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis

Gaut, Joseph P., Yeh, George C., Tran, Hung Duy, Byun, Jaeman, Henderson, Jeffrey P., Richter, Grace M., ...

The myeloperoxidase system of neutrophils uses hydrogen peroxide and chloride to generate hypochlorous acid, a potent bactericidal oxidant in vitro. In a mouse model of polymicrobial sepsis, we...

Synthetic LXR ligand inhibits the development of atherosclerosis in mice

Joseph, Sean B., McKilligin, Elaine, Pei, Liming, Watson, Michael A., Collins, Alan R., Laffitte, Bryan A., ...

The nuclear receptors LXRα and LXRβ have been implicated in the control of cholesterol and fatty acid metabolism in multiple cell types. Activation of these receptors stimulates cholesterol efflux...

Identification of macrophage liver X receptors as inhibitors of atherosclerosis

Tangirala, Rajendra K., Bischoff, Eric D., Joseph, Sean B., Wagner, Brandee L., Walczak, Robert, Laffitte, Bryan A., ...

Recent studies have identified the liver X receptors (LXRα and LXRβ) as important regulators of cholesterol metabolism and transport. LXRs control transcription of genes critical to a range of...

Increased atherosclerosis in myeloperoxidase-deficient mice

Brennan, Marie-Luise, Anderson, Melissa M., Shih, Diana M., Qu, Xiao-Dan, Wang, Xuping, Mehta, Asha C., ...

Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense and local tissue damage. Both MPO and its...

Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration

Baldus, Stephan, Eiserich, Jason P., Mani, Alireza, Castro, Laura, Figueroa, Mario, Chumley, Phillip, ...

Nitrotyrosine formation is a hallmark of vascular inflammation, with polymorphonuclear neutrophil–derived (PMN-derived) and monocyte-derived myeloperoxidase (MPO) being shown to catalyze this...

Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: New role for the NADPH oxidase in host defense

Rothfork, Jacob M., Timmins, Graham S., Harris, Michael N., Chen, Xian, Lusis, Aldons J., Otto, Michael, ...

Quorum sensing triggers virulence factor expression in medically important bacterial pathogens in response to a density-dependent increase in one or more autoinducing pheromones. Here, we show that...

Cis-acting expression quantitative trait loci in mice

Doss, Sudheer, Schadt, Eric E., Drake, Thomas A., Lusis, Aldons J.

We previously reported the analysis of genome-wide expression profiles and various diabetes-related traits in a segregating cross between inbred mouse strains C57BL/6J (B6) and DBA/2J (DBA). By...

Genomic analysis of metabolic pathway gene expression in mice

Ghazalpour, Anatole, Doss, Sudheer, Sheth, Sonal S, Ingram-Drake, Leslie A, Schadt, Eric E, Lusis, Aldons J, ...

In order to evaluate metabolic pathways associated with obesity, global gene-expression data were integrated with phenotypic and genetic segregation analyses, identifying 13 metabolic pathways the...

Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity

Wang, Susanna, Yehya, Nadir, Schadt, Eric E, Wang, Hui, Drake, Thomas A, Lusis, Aldons J

The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological...

Null mutation of myeloperoxidase in mice prevents mechanical activation of neutrophil lysis of muscle cell membranes in vitro and in vivo

Nguyen, Hal X, Lusis, Aldons J, Tidball, James G

Membrane lysis is a common and early defect in muscles experiencing acute injuries or inflammation. Although increased mechanical loading of muscles can induce inflammation and membrane lysis,...

Linkage of Genetic Determinants for Mouse β-Galactosidase Electrophoresis and Activity

Breen, Gail A. M., Lusis, Aldons J., Paigen, Kenneth

An electrophoretic polymorphism for β-galactosidase has been identified among common inbred strains of mice. It is inherited as a single Mendelian factor with two alleles showing codominant...

X-Linked and Autosomal Genes Controlling Mouse α-Galactosidase Expression

Lusis, Aldons J., West, John D.

Analysis of F2 and backcross animals has confirmed the X-chromosome linkage of Ags, the structural locus for mouse α-galactosidase. The position of Ags has been located in the X chromosome, 9...

Quantitative Trait Locus Analysis of Atherosclerosis in an Intercross Between C57BL/6 and C3H Mice Carrying the Mutant Apolipoprotein E Gene

Su, Zhiguang, Li, Yuhua, James, Jessica C., McDuffie, Marcia, Matsumoto, Alan H., Helm, Gregory A., ...

Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) differ significantly in atherosclerosis susceptibility and plasma lipid levels on the apolipoprotein E-deficient (apoE−/−) background when fed...

Complex Inheritance of the 5-Lipoxygenase Locus Influencing Atherosclerosis in Mice

Ghazalpour, Anatole, Wang, Xuping, Lusis, Aldons J., Mehrabian, Margarete

We previously mapped a locus on chromosome 6 with a large effect (LOD > 6) on aortic lesion size in a (C57BL/6J × CAST/Ei) F2 cross and identified arachidonate 5-lipoxygenase (5LO) as a candidate...

Integrating Genetic and Network Analysis to Characterize Genes Related to Mouse Weight

Ghazalpour, Anatole, Doss, Sudheer, Zhang, Bin, Wang, Susanna, Plaisier, Christopher, Castellanos, Ruth, ...

Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker...

Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis

Cases, Sylvaine, Smith, Steven J., Zheng, Yao-Wu, Myers, Heather M., Lear, Steven R., Sande, Eric, ...

Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the terminal and only...

Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase

Nathan, Lauren, Shi, Weibin, Dinh, Hillary, Mukherjee, Tapan K., Wang, Xuping, Lusis, Aldons J., ...

The effects of testosterone on early atherogenesis and the role of aromatase, an enzyme that converts testosterone to estrogens, were assessed in low density lipoprotein receptor-deficient male mice...

Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis

Gaut, Joseph P., Yeh, George C., Tran, Hung Duy, Byun, Jaeman, Henderson, Jeffrey P., Richter, Grace M., ...

The myeloperoxidase system of neutrophils uses hydrogen peroxide and chloride to generate hypochlorous acid, a potent bactericidal oxidant in vitro. In a mouse model of polymicrobial sepsis, we...

Synthetic LXR ligand inhibits the development of atherosclerosis in mice

Joseph, Sean B., McKilligin, Elaine, Pei, Liming, Watson, Michael A., Collins, Alan R., Laffitte, Bryan A., ...

The nuclear receptors LXRα and LXRβ have been implicated in the control of cholesterol and fatty acid metabolism in multiple cell types. Activation of these receptors stimulates cholesterol efflux...

Identification of macrophage liver X receptors as inhibitors of atherosclerosis

Tangirala, Rajendra K., Bischoff, Eric D., Joseph, Sean B., Wagner, Brandee L., Walczak, Robert, Laffitte, Bryan A., ...

Recent studies have identified the liver X receptors (LXRα and LXRβ) as important regulators of cholesterol metabolism and transport. LXRs control transcription of genes critical to a range of...

Increased atherosclerosis in myeloperoxidase-deficient mice

Brennan, Marie-Luise, Anderson, Melissa M., Shih, Diana M., Qu, Xiao-Dan, Wang, Xuping, Mehta, Asha C., ...

Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense and local tissue damage. Both MPO and its...

Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration

Baldus, Stephan, Eiserich, Jason P., Mani, Alireza, Castro, Laura, Figueroa, Mario, Chumley, Phillip, ...

Nitrotyrosine formation is a hallmark of vascular inflammation, with polymorphonuclear neutrophil–derived (PMN-derived) and monocyte-derived myeloperoxidase (MPO) being shown to catalyze this...

Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: New role for the NADPH oxidase in host defense

Rothfork, Jacob M., Timmins, Graham S., Harris, Michael N., Chen, Xian, Lusis, Aldons J., Otto, Michael, ...

Quorum sensing triggers virulence factor expression in medically important bacterial pathogens in response to a density-dependent increase in one or more autoinducing pheromones. Here, we show that...

Cis-acting expression quantitative trait loci in mice

Doss, Sudheer, Schadt, Eric E., Drake, Thomas A., Lusis, Aldons J.

We previously reported the analysis of genome-wide expression profiles and various diabetes-related traits in a segregating cross between inbred mouse strains C57BL/6J (B6) and DBA/2J (DBA). By...

Genomic analysis of metabolic pathway gene expression in mice

Ghazalpour, Anatole, Doss, Sudheer, Sheth, Sonal S, Ingram-Drake, Leslie A, Schadt, Eric E, Lusis, Aldons J, ...

In order to evaluate metabolic pathways associated with obesity, global gene-expression data were integrated with phenotypic and genetic segregation analyses, identifying 13 metabolic pathways the...

Combined Analysis of Genome Scans of Dutch and Finnish Families Reveals a Susceptibility Locus for High-Density Lipoprotein Cholesterol on Chromosome 16q

Pajukanta, Päivi, Allayee, Hooman, Krass, Kelly L., Kuraishy, Ali, Soro, Aino, Lilja, Heidi E., ...

Several genomewide screens have been performed to identify novel loci predisposing to unfavorable serum lipid levels and coronary heart disease (CHD). We hypothesized that the accumulating data of...

Linkage of Genetic Determinants for Mouse β-Galactosidase Electrophoresis and Activity

Breen, Gail A. M., Lusis, Aldons J., Paigen, Kenneth

An electrophoretic polymorphism for β-galactosidase has been identified among common inbred strains of mice. It is inherited as a single Mendelian factor with two alleles showing codominant...

X-Linked and Autosomal Genes Controlling Mouse α-Galactosidase Expression

Lusis, Aldons J., West, John D.

Analysis of F2 and backcross animals has confirmed the X-chromosome linkage of Ags, the structural locus for mouse α-galactosidase. The position of Ags has been located in the X chromosome, 9...

Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity

Wang, Susanna, Yehya, Nadir, Schadt, Eric E, Wang, Hui, Drake, Thomas A, Lusis, Aldons J

The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological...

Quantitative Trait Locus Analysis of Atherosclerosis in an Intercross Between C57BL/6 and C3H Mice Carrying the Mutant Apolipoprotein E Gene

Su, Zhiguang, Li, Yuhua, James, Jessica C., McDuffie, Marcia, Matsumoto, Alan H., Helm, Gregory A., ...

Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) differ significantly in atherosclerosis susceptibility and plasma lipid levels on the apolipoprotein E-deficient (apoE−/−) background when fed...

Null mutation of myeloperoxidase in mice prevents mechanical activation of neutrophil lysis of muscle cell membranes in vitro and in vivo

Nguyen, Hal X, Lusis, Aldons J, Tidball, James G

Membrane lysis is a common and early defect in muscles experiencing acute injuries or inflammation. Although increased mechanical loading of muscles can induce inflammation and membrane lysis,...

Complex Inheritance of the 5-Lipoxygenase Locus Influencing Atherosclerosis in Mice

Ghazalpour, Anatole, Wang, Xuping, Lusis, Aldons J., Mehrabian, Margarete

We previously mapped a locus on chromosome 6 with a large effect (LOD > 6) on aortic lesion size in a (C57BL/6J × CAST/Ei) F2 cross and identified arachidonate 5-lipoxygenase (5LO) as a candidate...

Integrating Genetic and Network Analysis to Characterize Genes Related to Mouse Weight

Ghazalpour, Anatole, Doss, Sudheer, Zhang, Bin, Wang, Susanna, Plaisier, Christopher, Castellanos, Ruth, ...

Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker...

Tissue-specific expression and regulation of sexually dimorphic genes in mice

Yang, Xia, Schadt, Eric E., Wang, Susanna, Wang, Hui, Arnold, Arthur P., Ingram-Drake, Leslie, ...

We report a comprehensive analysis of gene expression differences between sexes in multiple somatic tissues of 334 mice derived from an intercross between inbred mouse strains C57BL/6J and C3H/HeJ....

Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids

Gargalovic, Peter S., Imura, Minori, Zhang, Bin, Gharavi, Nima M., Clark, Michael J., Pagnon, Joanne, ...

Oxidized phospholipids are thought to promote atherogenesis by stimulating endothelial cells (ECs) to produce inflammatory cytokines, such as IL-8. In studies with mouse models, we previously...

Ligand activation of LXRβ reverses atherosclerosis and cellular cholesterol overload in mice lacking LXRα and apoE

Bradley, Michelle N., Hong, Cynthia, Chen, Mingyi, Joseph, Sean B., Wilpitz, Damien C., Wang, Xuping, ...

Liver X receptors (LXRs) α and β are transcriptional regulators of cholesterol homeostasis and potential targets for the development of antiatherosclerosis drugs. However, the specific roles of...

Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics

Meng, Haijin, Vera, Iset, Che, Nam, Wang, Xuping, Wang, Susanna S., Ingram-Drake, Leslie, ...

The genetic factors contributing to the complex disorder of myocardial calcification are largely unknown. Using a mouse model, we fine-mapped the major locus (Dyscalc1) contributing to the dystrophic...

Weighted gene coexpression network analysis strategies applied to mouse weight

Fuller, Tova F., Ghazalpour, Anatole, Aten, Jason E., Drake, Thomas A., Lusis, Aldons J., Horvath, Steve

Systems-oriented genetic approaches that incorporate gene expression and genotype data are valuable in the quest for genetic regulatory loci underlying complex traits. Gene coexpression network...

Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells

Gong, Ke Wei, Zhao, Wei, Li, Ning, Barajas, Berenice, Kleinman, Michael, Sioutas, Constantinos, ...

Gene expression analysis of human microvascular endothelial cells exposed to diesel exhaust particles and oxidized phospholipids revealed several upregulated gene modules, including genes involved in...

Mapping the Genetic Architecture of Gene Expression in Human Liver

Schadt, Eric E, Molony, Cliona, Chudin, Eugene, Hao, Ke, Yang, Xia, Lum, Pek Y, ...

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order...

High-Resolution Mapping of Gene Expression Using Association in an Outbred Mouse Stock

Ghazalpour, Anatole, Doss, Sudheer, Kang, Hyun, Farber, Charles, Wen, Ping-Zi, Brozell, Alec, ...

Quantitative trait locus (QTL) analysis is a powerful tool for mapping genes for complex traits in mice, but its utility is limited by poor resolution. A promising mapping approach is association...