title: Understanding our drugs and our diseases.
abstract: 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.
authors.affiliation: Departments of Genetics and Genomics, Roche Palo Alto, Palo Alto, CA 94304, USA.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Guo
authors.forename: Paul
authors.initials: P
authors.lastname: Weller
authors.forename: John
authors.initials: J
authors.lastname: Allard
authors.forename: Jonathan
authors.initials: J
authors.lastname: Usuka
authors.forename: Mohammad
authors.initials: M
authors.lastname: Masjedizadeh
authors.forename: Shao-Yong
authors.initials: SY
authors.lastname: Wu
authors.forename: Bill
authors.initials: B
authors.lastname: Fitch
authors.forename: Douglas
authors.initials: D
authors.lastname: Clark
authors.forename: J David
authors.initials: JD
authors.lastname: Clark
authors.forename: Steve
authors.initials: S
authors.lastname: Shafer
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.forename: Guochun
authors.initials: G
authors.lastname: Liao
authors.forename: Gary
authors.initials: G
authors.lastname: Peltz
mesh_terms: D000818:Animals; D019295:Computational Biology; D004353:Drug Evaluation, Preclinical; D014644:Genetic Variation; D016678:Genome; D006239:Haplotypes; D051379:Mice; D008957:Models, Genetic; D004364:Pharmaceutical Preparations; D040641:Quantitative Trait Loci
chemical_list: D004364:Pharmaceutical Preparations