Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 23 November 2001:
Vol. 294. no. 5547, pp. 1723 - 1726
DOI: 10.1126/science.1062117
Prev | Table of Contents | Next

Reports

A Genomic-Systems Biology Map for Cardiovascular Function

Monika Stoll,1 Allen W. Cowley Jr.,1 Peter J. Tonellato,12 Andrew S. Greene,1 Mary L. Kaldunski,1 Richard J. Roman,1 Pierre Dumas,13 Nicholas J. Schork,456 Zhitao Wang,12 Howard J. Jacob13*

With the draft sequence of the human genome available, there is a need to better define gene function in the context of systems biology. We studied 239 cardiovascular and renal phenotypes in 113 male rats derived from an F2 intercross and mapped 81 of these traits onto the genome. Aggregates of traits were identified on chromosomes 1, 2, 7, and 18. Systems biology was assessed by examining patterns of correlations ("physiological profiles") that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.

1 Department of Physiology,
2 Bioinformatics Research Center, and
3 Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA.
4 Case Western Reserve University, Cleveland, OH 44106, USA.
5 The Jackson Laboratory, Bar Harbor, ME 04609, USA.
6 Harvard School of Public Health, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: jacob{at}mcw.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
NOD x 129.H2g7 Backcross Delineates 129S1/SvImJ-Derived Genomic Regions Modulating Type 1 Diabetes Development in Mice.
E. H. Leiter, P. C. Reifsnyder, R. Wallace, R. Li, B. King, and G. C. Churchill (2009)
Diabetes 58, 1700-1703
   Abstract »    Full Text »    PDF »
Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences.
D. A. Blizard, A. Lionikas, D. J. Vandenbergh, T. Vasilopoulos, G. S. Gerhard, J. W. Griffith, L. C. Klein, J. T. Stout, H. A. Mack, J. M. Lakoski, et al. (2009)
Physiol Genomics 36, 158-166
   Abstract »    Full Text »    PDF »
Renal medullary 11{beta}-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension.
Y. Liu, R. J. Singh, K. Usa, B. C. Netzel, and M. Liang (2008)
Physiol Genomics 36, 52-58
   Abstract »    Full Text »    PDF »
Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat.
M. Fuse, N. Yokoi, M. Shinohara, T. Masuyama, R. Kitazawa, S. Kitazawa, and S. Seino (2008)
Physiol Genomics 35, 96-105
   Abstract »    Full Text »    PDF »
Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease.
D. L. Mattson, M. R. Dwinell, A. S. Greene, A. E. Kwitek, R. J. Roman, H. J. Jacob, and A. W. Cowley Jr. (2008)
Am J Physiol Renal Physiol 295, F837-F842
   Abstract »    Full Text »    PDF »
Renal Regional Proteomes in Young Dahl Salt-Sensitive Rats.
Z. Tian, A. S. Greene, K. Usa, I. R. Matus, J. Bauwens, J. L. Pietrusz, A. W. Cowley Jr, and M. Liang (2008)
Hypertension 51, 899-904
   Abstract »    Full Text »    PDF »
Systematic, Genome-Wide, Sex-Specific Linkage of Cardiovascular Traits in French Canadians.
O. Seda, J. Tremblay, D. Gaudet, P.-L. Brunelle, A. Gurau, E. Merlo, L. Pilote, S. N. Orlov, F. Boulva, M. Petrovich, et al. (2008)
Hypertension 51, 1156-1162
   Abstract »    Full Text »    PDF »
Chromosomal mapping of the genetic basis of hypertension and renal disease in FHH rats.
D. L. Mattson, M. R. Dwinell, A. S. Greene, A. E. Kwitek, R. J. Roman, A. W. Cowley Jr., and H. J. Jacob (2007)
Am J Physiol Renal Physiol 293, F1905-F1914
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor 1 Gene and Hypertension: From the Quantitative Trait Locus to Positional Analysis.
M. Tomaszewski, F. J. Charchar, M. D. Lynch, S. Padmanabhan, W. Y.S. Wang, W. H. Miller, W. Grzeszczak, C. Maric, E. Zukowska-Szczechowska, and A. F. Dominiczak (2007)
Circulation 116, 1915-1924
   Abstract »    Full Text »    PDF »
Multiple blood pressure loci on rat chromosome 13 attenuate development of hypertension in the Dahl S hypertensive rat.
C. Moreno, M. L. Kaldunski, T. Wang, R. J. Roman, A. S. Greene, J. Lazar, H. J. Jacob, and A. W. Cowley Jr. (2007)
Physiol Genomics 31, 228-235
   Abstract »    Full Text »    PDF »
Efficient transgenic rat production by a lentiviral vector.
M. Michalkiewicz, T. Michalkiewicz, A. M. Geurts, R. J. Roman, G. R. Slocum, O. Singer, D. Weihrauch, A. S. Greene, M. Kaldunski, I. M. Verma, et al. (2007)
Am J Physiol Heart Circ Physiol 293, H881-H894
   Abstract »    Full Text »    PDF »
Neuronal Responsiveness to Central Na+ in 2 Congenic Strains of Dahl Salt-Sensitive Rats.
B. S. Huang, M. Ahmad, A. Y. Deng, and F. H.H. Leenen (2007)
Hypertension 49, 1315-1320
   Abstract »    Full Text »    PDF »
Molecular Genetics of Experimental Hypertension and the Metabolic Syndrome: From Gene Pathways to New Therapies.
M. Pravenec and T. W. Kurtz (2007)
Hypertension 49, 941-952
   Abstract »    Full Text »    PDF »
A Candidate Hypertension Gene: Will SPON1 Hold Salt and Water?.
S. Heximer and M. Husain (2007)
Circ. Res. 100, 940-942
   Full Text »    PDF »
Novel double-congenic strain reveals effects of spontaneously hypertensive rat chromosome 2 on specific lipoprotein subfractions and adiposity.
O. Seda, L. Sedova, F. Liska, D. Krenova, V. Prejzek, L. Kazdova, J. Tremblay, P. Hamet, and V. Kren (2007)
Physiol Genomics 27, 95-102
   Abstract »    Full Text »    PDF »
Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3.
S. J. Lee, J. Liu, A. M. Westcott, J. A. Vieth, S. J. DeRaedt, S. Yang, B. Joe, and G. T. Cicila (2006)
Genetics 174, 2203-2213
   Abstract »    Full Text »    PDF »
A loss of genome buffering capacity of Dahl salt-sensitive model to modulate blood pressure as a cause of hypertension.
S. Charron, R. Lambert, V. Eliopoulos, C. Duong, A. Menard, J. Roy, and A. Y. Deng (2005)
Hum. Mol. Genet. 14, 3877-3884
   Abstract »    Full Text »    PDF »
Impact of genomics on research in the rat.
J. Lazar, C. Moreno, H. J. Jacob, and A. E. Kwitek (2005)
Genome Res. 15, 1717-1728
   Abstract »    Full Text »    PDF »
Genetic variations of tubular sodium reabsorption leading to "primary" hypertension: from gene polymorphism to clinical symptoms.
G. Bianchi (2005)
Am J Physiol Regulatory Integrative Comp Physiol 289, R1536-R1549
   Abstract »    Full Text »    PDF »
Severe hypertension caused by alleles from normotensive Lewis for a quantitative trait locus on chromosome 2.
V. Eliopoulos, J. Dutil, Y. Deng, M. Grondin, and A. Y. Deng (2005)
Physiol Genomics 22, 70-75
   Abstract »    Full Text »    PDF »
Rf-2 Gene Modulates Proteinuria and Albuminuria Independently of Changes in Glomerular Permeability in the Fawn-Hooded Hypertensive Rat.
A. Rangel-Filho, M. Sharma, Y. H. Datta, C. Moreno, R. J. Roman, Y. Iwamoto, A. P. Provoost, J. Lazar, and H. J. Jacob (2005)
J. Am. Soc. Nephrol. 16, 852-856
   Full Text »    PDF »
Multiple Quantitative Trait Loci for Blood Pressure Interacting Epistatically and Additively on Dahl Rat Chromosome 2.
J. Dutil, V. Eliopoulos, J. Tremblay, P. Hamet, S. Charron, and A. Y. Deng (2005)
Hypertension 45, 557-564
   Abstract »    Full Text »    PDF »
Recommendations for Blood Pressure Measurement in Humans and Experimental Animals: Part 2: Blood Pressure Measurement in Experimental Animals. A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research.
T. W. Kurtz, K. A. Griffin, A. K. Bidani, R. L. Davisson, and J. E. Hall (2005)
Arterioscler. Thromb. Vasc. Biol. 25, e22-e33
   Abstract »    Full Text »    PDF »
Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta.
D. Gauguier, J. Behmoaras, K. Argoud, S. P. Wilder, C. Pradines, M. T. Bihoreau, M. Osborne-Pellegrin, and M. P. Jacob (2005)
Hypertension 45, 460-466
   Abstract »    Full Text »    PDF »
The landscape of genetic complexity across 5,700 gene expression traits in yeast.
R. B. Brem and L. Kruglyak (2005)
PNAS 102, 1572-1577
   Abstract »    Full Text »    PDF »
Recommendations for Blood Pressure Measurement in Humans and Experimental Animals: Part 2: Blood Pressure Measurement in Experimental Animals: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research.
T. W. Kurtz, K. A. Griffin, A. K. Bidani, R. L. Davisson, and J. E. Hall (2005)
Hypertension 45, 299-310
   Abstract »    Full Text »    PDF »
Mapping the Genetic Determinants of Hypertension, Metabolic Diseases, and Related Phenotypes in the Lyon Hypertensive Rat.
M. Bilusic, A. Bataillard, M. R. Tschannen, L. Gao, N. E. Barreto, M. Vincent, T. Wang, H. J. Jacob, J. Sassard, and A. E. Kwitek (2004)
Hypertension 44, 695-701
   Abstract »    Full Text »    PDF »
Thematic review series: The Pathogenesis of Atherosclerosis. Toward a biological network for atherosclerosis.
A. Ghazalpour, S. Doss, X. Yang, J. Aten, E. M. Toomey, A. Van Nas, S. Wang, T. A. Drake, and A. J. Lusis (2004)
J. Lipid Res. 45, 1793-1805
   Abstract »    Full Text »    PDF »
Genetic kininogen deficiency contributes to aortic aneurysm formation but not to atherosclerosis.
E. Kaschina, M. Stoll, M. Sommerfeld, U. M. Steckelings, R. Kreutz, and T. Unger (2004)
Physiol Genomics 19, 41-49
   Abstract »    Full Text »    PDF »
Genomics and the circulation.
M. V. Podgoreanu and D. A. Schwinn (2004)
Br. J. Anaesth. 93, 140-148
   Abstract »    Full Text »    PDF »
Integration of the Rat Recombination and EST Maps in the Rat Genomic Sequence and Comparative Mapping Analysis With the Mouse Genome.
S. P. Wilder, M.-T. Bihoreau, K. Argoud, T. K. Watanabe, M. Lathrop, and D. Gauguier (2004)
Genome Res. 14, 758-765
   Abstract »    Full Text »    PDF »
Integrated and Sequence-Ordered BAC- and YAC-Based Physical Maps for the Rat Genome.
M. Krzywinski, J. Wallis, C. Gosele, I. Bosdet, R. Chiu, T. Graves, O. Hummel, D. Layman, C. Mathewson, N. Wye, et al. (2004)
Genome Res. 14, 766-779
   Abstract »    Full Text »    PDF »
Rat model of familial combined hyperlipidemia as a result of comparative mapping.
T. Ueno, J. Tremblay, J. Kunes, J. Zicha, Z. Dobesova, Z. Pausova, A. Y. Deng, Y.-L. Sun, H. J. Jacob, and P. Hamet (2004)
Physiol Genomics 17, 38-47
   Abstract »    Full Text »    PDF »
Influence of diet and genetics on hypertension and renal disease in Dahl salt-sensitive rats.
D. L. Mattson, M. P. Kunert, M. L. Kaldunski, A. S. Greene, R. J. Roman, H. J. Jacob, and A. W. Cowley Jr (2004)
Physiol Genomics 16, 194-203
   Abstract »    Full Text »    PDF »
High throughput gene expression profiling: a molecular approach to integrative physiology.
M. Liang, A. W. Cowley Jr, and A. S. Greene (2004)
J. Physiol. 554, 22-30
   Abstract »    Full Text »    PDF »
Identifying genes and genetic variation underlying human diseases and complex phenotypes via recombination mapping.
U. Broeckel and N. J. Schork (2004)
J. Physiol. 554, 40-45
   Abstract »    Full Text »    PDF »
Application of chromosomal substitution techniques in gene-function discovery.
A. W. Cowley Jr, R. J. Roman, and H. J. Jacob (2004)
J. Physiol. 554, 46-55
   Abstract »    Full Text »    PDF »
Functional genomics in rodent models of hypertension.
M. W. McBride, F. J. Charchar, D. Graham, W. H. Miller, P. Strahorn, F. J. Carr, and A. F. Dominiczak (2004)
J. Physiol. 554, 56-63
   Abstract »    Full Text »    PDF »
Genomic map of cardiovascular phenotypes of hypertension in female Dahl S rats.
C. Moreno, P. Dumas, M. L. Kaldunski, P. J. Tonellato, A. S. Greene, R. J. Roman, Q. Cheng, Z. Wang, H. J. Jacob, and A. W. Cowley Jr (2003)
Physiol Genomics 15, 243-257
   Abstract »    Full Text »    PDF »
Pleiotropy, Homeostasis, and Functional Networks Based on Assays of Cardiovascular Traits in Genetically Randomized Populations.
J. H. Nadeau, L. C. Burrage, J. Restivo, Y.-H. Pao, G. Churchill, and B. D. Hoit (2003)
Genome Res. 13, 2082-2091
   Abstract »    Full Text »    PDF »
Using Mice to Dissect Genetic Factors in Atherosclerosis.
H. Allayee, A. Ghazalpour, and A. J. Lusis (2003)
Arterioscler. Thromb. Vasc. Biol. 23, 1501-1509
   Abstract »    Full Text »    PDF »
Automated Detection of Informative Combined Effects in Genetic Association Studies of Complex Traits.
N. Tahri-Daizadeh, D.-A. Tregouet, V. Nicaud, N. Manuel, F. Cambien, and L. Tiret (2003)
Genome Res. 13, 1952-1960
   Abstract »    Full Text »    PDF »
Genetic Models in Applied Physiology: Invited Review: Functional genomics in the mouse: powerful techniques for unraveling the basis of human development and disease.
C. W. Bogue (2003)
J Appl Physiol 94, 2502-2509
   Abstract »    Full Text »    PDF »
Genome Informatics: Current Status and Future Prospects.
R. L. Winslow and M. S. Boguski (2003)
Circ. Res. 92, 953-961
   Abstract »    Full Text »    PDF »
Genomics and homeostasis.
A. W. Cowley Jr. (2003)
Am J Physiol Regulatory Integrative Comp Physiol 284, R611-R627
   Abstract »    Full Text »    PDF »
Genetics of Obesity and Type 2 Diabetes: Tracking Pathogenic Traits During the Predisease Period.
P. Bougneres (2002)
Diabetes 51, S295-303
   Abstract »    Full Text »    PDF »
Identification of Hypertension-Related QTLs in African American Sib Pairs.
T. A. Kotchen, U. Broeckel, C. E. Grim, P. Hamet, H. Jacob, M. L. Kaldunski, J. M. Kotchen, N. J. Schork, P. J. Tonellato, and A. W. Cowley Jr (2002)
Hypertension 40, 634-639
   Abstract »    Full Text »    PDF »
Genetic approaches to the molecular understanding of type 2 diabetes.
M. I. McCarthy and P. Froguel (2002)
Am J Physiol Endocrinol Metab 283, E217-E225
   Abstract »    Full Text »    PDF »
Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions of angiotensin II.
M. Szentivanyi Jr., A.-P. Zou, D. L. Mattson, P. Soares, C. Moreno, R. J. Roman, and A. W. Cowley Jr. (2002)
Am J Physiol Regulatory Integrative Comp Physiol 283, R266-R272
   Abstract »    Full Text »    PDF »
Consomic Rats for the Identification of Genes and Pathways Underlying Cardiovascular Disease.
R.J. ROMAN, A.W. COWLEY, A. GREENE, A.E. KWITEK, P.J. TONELLATO, and H.J. JACOB (2002)
Cold Spring Harb Symp Quant Biol 67, 309-316
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)