Guo Yingying, Weller Paul, Allard John, Usuka Jonathan, Masjedizadeh Mohammad, Wu Shao-Yong, Fitch Bill, Clark Douglas, Clark J David, Shafer Steve, Wang Jianmei, Liao Guochun, Peltz Gary
Departments of Genetics and Genomics, Roche Palo Alto, Palo Alto, CA 94304, USA.
Proc Am Thorac Soc. 2006 Jul;3(5):409-12. doi: 10.1513/pats.200601-014AW.
Analysis of mouse genetic models of human disease-associated traits has provided important insight into the pathogenesis of human disease. As one example, analysis of a murine genetic model of osteoporosis demonstrated that genetic variation within the 15-lipoxygenase (Alox15) gene affected peak bone mass, and that treatment with inhibitors of this enzyme improved bone mass and quality in rodent models. However, the method that has been used to analyze mouse genetic models is very time consuming, inefficient, and costly. To overcome these limitations, a computational method for analysis of mouse genetic models was developed that markedly accelerates the pace of genetic discovery. It was used to identify a genetic factor affecting the rate of metabolism of warfarin, an anticoagulant that is commonly used to treat clotting disorders. Computational analysis of a murine genetic model of narcotic drug withdrawal suggested a potential new approach for treatment of narcotic drug addiction. Thus, the results derived from computational mouse genetic analysis can suggest new treatment strategies, and can provide new information about currently available medicines.
对与人类疾病相关性状的小鼠遗传模型进行分析，为深入了解人类疾病的发病机制提供了重要线索。例如，对骨质疏松症的小鼠遗传模型分析表明，15-脂氧合酶（Alox15）基因内的遗传变异会影响峰值骨量，并且用该酶的抑制剂进行治疗可改善啮齿动物模型的骨量和骨质。然而，用于分析小鼠遗传模型的方法非常耗时、低效且成本高昂。为克服这些局限性，开发了一种用于分析小鼠遗传模型的计算方法，该方法显著加快了基因发现的速度。它被用于鉴定影响华法林代谢速率的一个遗传因素，华法林是一种常用于治疗凝血障碍的抗凝剂。对麻醉药物戒断的小鼠遗传模型进行的计算分析提出了一种治疗麻醉药物成瘾的潜在新方法。因此，通过计算小鼠遗传分析得出的结果可以提出新的治疗策略，并能提供有关现有药物的新信息。
