Williams Scott M, Haines Jonathan L, Moore Jason H
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Bioessays. 2004 Feb;26(2):170-9. doi: 10.1002/bies.10401.
The study of the genetics of complex human disease has met with limited success. Many findings with candidate genes fail to replicate despite seemingly overwhelming physiological data implicating the genes. In contrast, animal model studies of the same genes and disease models usually have more consistent results. We propose that one important reason for this is the ability to control genetic background in animal studies. The fact that controlling genetic background can produce more consistent results suggests that the failure to replicate human findings in the same diseases is due to variation in interacting genes. Hence, the contrasting nature of the findings from the different study designs indicates the importance of non-additive genetic effects on human disease. We discuss these issues and some methodological approaches that can detect multilocus effects, using hypertension as a model disease. This article contains supplementary material, which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html.
对复杂人类疾病遗传学的研究成效有限。尽管有看似确凿的生理数据表明某些基因与疾病相关，但许多针对候选基因的研究结果却无法重复验证。相比之下，对相同基因和疾病模型的动物模型研究通常会得到更为一致的结果。我们认为，造成这种情况的一个重要原因是在动物研究中能够控制遗传背景。控制遗传背景能够产生更一致结果这一事实表明，在相同疾病中无法重复人类研究结果是由于相互作用基因的变异所致。因此，不同研究设计结果的差异性质表明了非加性遗传效应在人类疾病中的重要性。我们以高血压作为模型疾病，讨论这些问题以及一些能够检测多位点效应的方法。本文包含补充材料，可在BioEssays网站（http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html）查看。
