Statistical Analysis of QTL Crosses and Gene Expression Arrays This project will apply newly developed statistical methods to experimental data obtained form rodent models of hypertension in order to identify genes and pathways that underlie blood pressure regulation in mammals. The first component, quantitative trait locus (QTL) mapping, will identify polymorphic loci that affect blood pressure in rodents. Epistasis analysis will be used to identify loci that participate in common biochemical pathways. The second component, gene expression microarray analysis, will identify changes in the expression of genes in tissue samples. The analysis of expression data will identify the downstream consequences of allelic variation at both QTL and candidate genes. The combination of a phenotype driven approach, QTL mapping, with a gene driven approach, expression analysis, will allow us to identify and characterize the effects of allelic variations that lead to hypertension. Our analyses of these two types of data will generate testable hypotheses about specific genes and pathways related to hypertension in rodents that can then be extended to human hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
2P50HL055001-06
Application #
6441102
Study Section
Special Emphasis Panel (ZHL1)
Project Start
1996-02-01
Project End
2006-01-31
Budget Start
Budget End
Support Year
6
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Shenouda, Sherene M; Johns, Conrado; Kintsurashvili, Ekaterina et al. (2006) Long-term inhibition of the central alpha(2B)-adrenergic receptor gene via recombinant AAV-delivered antisense in hypertensive rats. Am J Hypertens 19:1135-43
Cardoso de Carvalho, Fabio; Bregagnollo, Edson; Santos Silva, Vanessa et al. (2006) Frequency of coronary artery disease in patients with renal artery stenosis without clinical manifestations of coronary insufficiency. Am J Hypertens 19:1125-8
Duka, Arvi; Schwartz, Faina; Duka, Irena et al. (2006) A novel gene (Cmya3) induced in the heart by angiotensin II-dependent but not salt-dependent hypertension in mice. Am J Hypertens 19:275-81
Cui, Jing; Melista, Efthymia; Chazaro, Irmarie et al. (2005) Sequence variation of bradykinin receptors B1 and B2 and association with hypertension. J Hypertens 23:55-62
Manolis, Athanasios J; Iraklianou, Stella; Pittaras, Andreas et al. (2005) Arterial compliance changes in diabetic normotensive patients after angiotensin-converting enzyme inhibition therapy. Am J Hypertens 18:18-22
Ignjacev-Lazich, Ivana; Kintsurashvili, Ekaterina; Johns, Conrado et al. (2005) Angiotensin-converting enzyme regulates bradykinin receptor gene expression. Am J Physiol Heart Circ Physiol 289:H1814-20
Russo, Christopher J; Melista, Efthymia; Cui, Jing et al. (2005) Association of NEDD4L ubiquitin ligase with essential hypertension. Hypertension 46:488-91
Schwartz, Faina; Duka, Arvi; Duka, Irena et al. (2004) Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression. Am J Physiol Heart Circ Physiol 287:H1957-66
Elijovich, Fernando; Laffer, Cheryl L; Schiffrin, Ernesto L et al. (2004) Endothelin-aldosterone interaction and proteinuria in low-renin hypertension. J Hypertens 22:573-82
Erlich, Porat M; Cui, Jing; Chazaro, Irmarie et al. (2003) Genetic variants of WNK4 in whites and African Americans with hypertension. Hypertension 41:1191-5

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