Toxicogenetics: population-based testing of drug and chemical safety in mouse models.
Toxicogenetics: population-based testing of drug and chemical safety in mouse models.
复制标题
DOI：
10.2217/pgs.10.100
复制
发表时间：
2010-08
期刊：
影响因子：
2.1
通讯作者：
Threadgill DW
中科院分区：
文献类型：
--
作者：
Rusyn I;Gatti DM;Wiltshire T;Kleeberger SR;Threadgill DW
密集基因分型成本的快速下降正在为新的基于DNA序列的实验室测试快速进入临床实践铺平道路，并最终帮助实现“个性化”治疗的前景。这些进展是基于对遗传学作为科学中的一个重要方面以及调查药理学和毒理学实践的日益认识。在临床方面，监管机构和制药行业都希望，及早识别易发生药物不良反应的个人，将使市场上的优势药物继续存在，造福绝大多数潜在患者。在环境健康保护方面，显然需要更好的科学来确定人群中易受化学品不利影响的范围和原因，以便确定适当的监管限制。在这两种情况下，大多数研究工作都集中在人类全基因组关联研究上，需要对每个受试者进行从头开始的基因分型。与此同时，在啮齿动物模型(如小鼠)中进行基于群体的临床前安全性测试的力量仍有待充分开发。在这里，我们重点介绍了在机械毒理学研究中利用小鼠作为一个物种的DNA序列和遗传多样性知识的可用方法。我们假设，适当的基因定义的小鼠模型可以与来自人类研究的有限数据相结合，不仅可以发现易感性的遗传决定因素，而且还可以了解毒性的分子基础。
The rapid decline in the cost of dense genotyping is paving the way for new DNA sequence-based laboratory tests to move quickly into clinical practice, and to ultimately help realize the promise of ‘personalized’ therapies. These advances are based on the growing appreciation of genetics as an important dimension in science and the practice of investigative pharmacology and toxicology. On the clinical side, both the regulators and the pharmaceutical industry hope that the early identification of individuals prone to adverse drug effects will keep advantageous medicines on the market for the benefit of the vast majority of prospective patients. On the environmental health protection side, there is a clear need for better science to define the range and causes of susceptibility to adverse effects of chemicals in the population, so that the appropriate regulatory limits are established. In both cases, most of the research effort is focused on genome-wide association studies in humans where de novo genotyping of each subject is required. At the same time, the power of population-based preclinical safety testing in rodent models (e.g., mouse) remains to be fully exploited. Here, we highlight the approaches available to utilize the knowledge of DNA sequence and genetic diversity of the mouse as a species in mechanistic toxicology research. We posit that appropriate genetically defined mouse models may be combined with the limited data from human studies to not only discover the genetic determinants of susceptibility, but to also understand the molecular underpinnings of toxicity.
登录
查看更多内容
影响因子：
3.7
作者：
Alberts, Rudi;Terpstra, Peter;Li, Yang;Breitling, Rainer;Nap, Jan-Peter;Jansen, Ritsert C.
通讯作者：
Jansen, Ritsert C.
影响因子：
4.5
作者：
Fry RC;Navasumrit P;Valiathan C;Svensson JP;Hogan BJ;Luo M;Bhattacharya S;Kandjanapa K;Soontararuks S;Nookabkaew S;Mahidol C;Ruchirawat M;Samson LD
通讯作者：
Samson LD
影响因子：
2.1
作者：
Becquemont, Laurent
通讯作者：
Becquemont, Laurent
DOI：
10.1164/rccm.200509-1527oc
发表时间：
2007-04-15
影响因子：
24.7
作者：
Cho, Hye-Youn;Morgan, Daniel L.;Kleeberger, Steven R.
通讯作者：
Kleeberger, Steven R.
影响因子：
4.2
作者：
Drake, Thomas A;Schadt, Eric E;Lusis, Aldons J
通讯作者：
Lusis, Aldons J