New target regions for human hypertension via comparative genomics

被引:181
作者
Stoll, M
Kwitek-Black, AE
Cowley, AW
Harris, EL
Harrap, SB
Krieger, JE
Printz, MP
Provoost, AP
Sassard, J
Jacob, HJ
机构
[1] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
[2] Univ Otago, Dept Surg, Dunedin, New Zealand
[3] Univ Otago, Ctr Gene Res, Dunedin, New Zealand
[4] Univ Melbourne, Dept Physiol, Parkville, Vic 3052, Australia
[5] Univ Sao Paulo, Sch Med, Mol Biol Lab, Sao Paulo, Brazil
[6] Univ Sao Paulo, Sch Med, Dept Med, Sao Paulo, Brazil
[7] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[8] Erasmus Univ, Dept Pediat Surg, NL-3000 DR Rotterdam, Netherlands
[9] CNRS, Dept Physiol & Clin Pharmacol, ESA 5014, Lyon, France
关键词
D O I
10.1101/gr.10.4.473
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Models of human disease have long been used to understand the basic pathophysiology of disease and to facilitate the discovery of new therapeutics. However, as long as models have been used there have been debates about the utility of these models and their ability to mimic clinical disease at the phenotypic level. The application of generic studies to both humans and model systems allows for a new paradigm, whereby a novel comparative genomics strategy combined with phenotypic correlates can be used to bridge between clinical relevance and model utility. This study presents a comparative genomic map for "candidate hypertension loci in humans" based on translating QTLs between rat and human, predicting 26 chromosomal regions in the human genome that are very likely to harbor hypertension genes. The predictive power appears robust, as several of these regions have also been implicated in mouse, suggesting that these regions represent primary targets for the development of SNPs for linkage disequilibrium testing in humans and/or provide a means to select specific models for additional functional studies and the development of new therapeutics.
引用
收藏
页码:473 / 482
页数:10
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