The value of animal models in predicting genetic susceptibility to complex diseases such as rheumatoid arthritis 英文参考文献.docVIP

Available online /content/11/3/226 Review The value of animal models in predicting genetic susceptibility to complex diseases such as rheumatoid arthritis Emma Ahlqvist1,*, Malin Hultqvist1,* and Rikard Holmdahl1,2 1Medical Inflammation Research, Lund University, C12 BMC, 221 84 Lund, Sweden 2Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles v?g 2, 171 77 Stockholm, Sweden *These authors contributed equally to this work Corresponding author: Rikard Holmdahl, rikard.holmdahl@ki.se Published: 19 May 2009 Arthritis Research Therapy 2009, 11:226 (doi:10.1186/ar2600) This article is online at /content/11/3/226 ? 2009 BioMed Central Ltd Abstract population to find regions that are overrepresented in patients. This increases mapping precision dramatically but it requires large repositories of patient materials and very closely spaced genetic markers, creating a need for correction for multiple testing, which raises the threshold for claiming statistical significance. Until recently, candidate gene studies were the only realistic way to utilize patient materials for association studies. The major disadvantage of candidate studies is the need for a starting hypothesis to choose candidates. The most interesting prospect of gene mapping, however, is that hypothesis-free mapping can point to previously unknown and unexpected disease pathways. For a long time, genetic studies of complex diseases were most successfully conducted in animal models. However, the field of genetics is now rapidly evolving, and human genetics has also started to produce strong candidate genes for complex diseases. This raises the question of how to continue gene-finding attempts in animals and how to use animal models to enhance our understanding of gene function. In this review we summarize the uses and advantages of animal