Stoll M, Kwitek-Black A E, Cowley A W, Harris E L, Harrap S B, Krieger J E, Printz M P, Provoost A P, Sassard J, Jacob H J
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Genome Res. 2000 Apr;10(4):473-82. doi: 10.1101/gr.10.4.473.
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 genetic 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.
人类疾病模型长期以来一直被用于理解疾病的基本病理生理学，并促进新疗法的发现。然而，自从使用模型以来，关于这些模型的效用以及它们在表型水平上模拟临床疾病的能力一直存在争议。将基因研究应用于人类和模型系统带来了一种新的范式，即一种新颖的比较基因组学策略与表型相关性相结合，可用于在临床相关性和模型效用之间架起桥梁。本研究基于大鼠和人类之间的数量性状基因座（QTL）转换，给出了“人类候选高血压基因座”的比较基因组图谱，预测了人类基因组中26个很可能含有高血压基因的染色体区域。这种预测能力似乎很强，因为其中几个区域在小鼠中也有涉及，这表明这些区域是开发用于人类连锁不平衡测试的单核苷酸多态性（SNP）的主要靶点，和/或提供了一种手段来选择特定模型进行额外的功能研究和开发新疗法。
