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Principal Investigator:
Bina Joe, Ph.D. Associate Professor
| RESEARCH |
Genetic studies of complex polygenic traits such as blood pressure are primary conducted with the view to map, identify and ascertain the magnitude of change imparted by each of the underlying contributing genetic factors. The scope of such studies conducted in humans alone is thwarted by several confounding factors including genetic heterogeneity, low penetrance and uncontrolled environmental factors. Rat models of hypertension have served as tools to study the genetic control of blood pressure with minimal interferences from these confounding factors. These include the inbred hypertensive strains, the consomic strains and the congenic strains. In our laboratory, we have constructed congenic strains derived from the Dahl salt-sensitive (S) rat as genetic tools and located and fine-mapped several quantitative trait loci to regions containing as few as two annotations to <30 annotations. Ongoing work is focused on detecting variants and assigning causation to the variants responsible for the observed effect on blood pressure. To this end, we are combining further substitution mapping with the development of transgenics, transcriptome analysis and proteomic analysis. These studies in rat models are expected to serve as potential leads for translational genetic analysis of human essential hypertension.
| FUNDING |
Our Research is funded through RO1 grants (HL075414, HL020176 and HL020176) from the National Heart Lung and Blood Institute of NIH.
1. Joe B, Saad Y, Lee N, Frank B, Achinike O, Luu T, Gopalakrishnan K, Toland E, Farms P, Yerga-Woolwine S, Manickavasagam E, Rapp J, Garrett M, Coe D, Apte S, Rankinen T, Pérusse L, Ehret G, Ganesh S, Cooper R, O'Connor A, Rice T, Weder A, Chakravarti A, Rao D, Bouchard C. Positional Identification of variants of Adamts16 linked to inherited hypertension. Hum Mol Genet 18: 2825-2838, 2009.
2. Tietjen, G.E., Herial, N.A., Utley, C, White, L, Yerga-Woolwine, S, Joe, B. Association of von Willibrand factor activity with ACE I/D and MTHFR C677T polymorphisms in migraine. Cephalalgia (In press) 2009.
3. Cicila, G.T., Morgan, E.E., Lee, S.J.,Farms, P., Yerga-Woolwine, S., Toland, E.J.,Ramdath, R. S., Gopalakrishnan, K., Bohman, K., Nestor-Kalinoski, A.L. Khuder, S.A., Joe, B. Epistatic Genetic Determinants of Blood Pressure and Mortality in a Salt-sensitive Hypertension Model. Hypertension 53:725, 2009.
4. Toland E, Yerga-Woolwine S, Farms P, Cicila GT, Saad Y and B. Joe. Blood Pressure and Proteinuria Effects of Multiple Quantitative Trait Loci on Rat Chromosome 9 that Differentiate the Spontaneously Hypertensive Rat from the Dahl Salt-sensitive Rat. J Hypertension 26: 2134-2141, 2008.
5. Saad Y, Toland E, Yerga-Woolwine S, Farms P and Joe B. Congenic mapping of a blood pressure QTL region on rat chromosome 10 using the Dahl Salt-sensitive rat with introgressed alleles from the Milan normotensive strain. Mamm. Genome 19: 85-91, 2008.(Featured on the cover).
6. Toland E, Saad Y, Yerga-Woolwine S, Ummel S, Farms S, Ramdath R, Frank BC, Lee NH and Joe B. Closely linked non-additive blood pressure quantitative trait loci. Mamm. Genome 19: 209-218, 2008.
7. Klemcke HG, Baer DG, Pankratz VS, Cox A, Cortez DS, Garrett MR, Joe, B, Ryan KL. Is survival time after hemorrhage a heritable, quantitative trait? An initial assessment. Shock 29: 748-753, 2008.
8. Saad Y, Yerga-Woolwine S, Saikumar J, Farms P, Manickavasagam E, Toland E and Joe B. Congenic interval mapping of RNO10 reveals a complex cluster of closely-linked genetic determinants of blood pressure. Hypertension 50:891-898, 2007.
9. Lee NH, Haas BJ, Letwin NE, Frank BC, Luu TV, Sun C, Yerga-Woolwine S, Farms P, Manickavasagam E, Joe B. Cross-talk of expression quantitative trait loci within two interacting blood pressure quantitative trait loci. Hypertension 50: 1126-1133, 2007.
10. Saad Y, Garrett MR, Manickavasagam E, Yerga-Woolwine S, Farms P, Radecki, T, Joe, B. Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants within a novel 1.17 Mb Blood Pressure QTL region. Genomics 89: 343-353, 2007.
11. Joe, B. and Garrett M.R. Genetic studies of inherited hypertension in the rat. Handbook of Hypertension (Elsevier) 24: A. Dominiczak and JM Connell (Editors): Genetics of Inherited Hypertension in the Rat; 177-200, 2007.
12. Lee SJ, Liu J, Wescott AM, Veith JA, DeRaedt SJ, Yang S, Joe, B, Cicila GT. Substitution mapping in Dahl rats identifies two distinct blood pressure quantitative trait loci within 1.12Mb and 1.25Mb intervals on chromosome 3. Genetics 174:2203-2213, 2006.
13. Garrett MR, Joe, B, Yerga-Woolwine S. Genetic Linkage of Urinary Albumin Excretion in Dahl Salt-Sensitive Rats: Influence of Dietary Salt and Confirmation using Congenic Strains. Physiological Genomics 13: 39-49, 2006.
14. Joe, B, Verratti K, Letwin NE, Garrett MR, Lee NH, Rapp JP. Transcriptional profiling with a blood pressure QTL interval-specific oligonucleotide array. Physiological Genomics 23: 318- 326, 2005.
| PEOPLE |
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Dr.Kathirvel Gopalakrishnan |
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Dr.Sivarajan Kumarasamy
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Dr.Thangavel Jayakumar |
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Shane Yerga-Woowine |
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Phyllis Farms
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Edward Toland |
Past Associates:
Dr. Jagannath Saikumar-Graduate Student (Graduated 2006)
Seema Dhindaw- Graduate Student (Graduated 2006)
Dr. Suresh Koneshwaran-Cardiology fellow
Hilary Good-Research Technician
Dr. Ezhilarasi Manickavasagam-Research Technician
Dr. Tracy Radecki-Research Technician
Dr. Sudha Warrier-Postdoctoral Fellow
Dr. Yasser Saad-Research Assistant Professor
Dr. Michael R. Garrett- Assistant Professor
Prof. John P. Rapp- Professor
Summer trainees:
Jeremy Nixon - IMAGINE2 program 2008
Riley Sproul- REACH program 2007
William Schnackel- Medical student summer program 2007
Heidi Haufmann- SURF program 2006
Amal Dudar- UT main campus summer program 2006
Steven Ummel- SURF program 2002
| LINKS |
