Department of Medicine and Kidney Disease Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
J Am Soc Nephrol. 2010 Mar;21(3):398-405. doi: 10.1681/ASN.2009080881. Epub 2010 Feb 4.
The increasing numbers of patients with chronic kidney disease combined with no satisfying interventions for preventing or curing the disease emphasize the need to better understand the genes involved in the initiation and progression of complex renal diseases, their interactions with other host genes, and the environment. Linkage and association studies in human, rat, and mouse have been successful in identifying genetic loci for various disease-related phenotypes but have thus far not been very successful identifying underlying genes. The purpose of this review is to summarize the progress in human, rat, and mouse genetic studies to show the concordance between the loci among the different species. The collective utilization of human and nonhuman mammalian datasets and resources can lead to a more rapid narrowing of disease loci and the subsequent identification of candidate genes. In addition, genes identified through these methods can be further characterized and investigated for interactions using animal models, which is not possible in humans.
慢性肾脏病患者数量不断增加,而目前尚无令人满意的干预措施来预防或治疗这种疾病,这强调了需要更好地了解参与复杂肾脏疾病发生和进展的基因、它们与其他宿主基因的相互作用以及环境。在人类、大鼠和小鼠中进行的连锁和关联研究已成功确定了各种与疾病相关表型的遗传位点,但迄今为止,确定潜在基因的成功率并不高。本文综述的目的是总结人类、大鼠和小鼠遗传研究的进展,以显示不同物种之间基因座的一致性。人类和非人类哺乳动物数据集和资源的综合利用可以更快速地缩小疾病基因座的范围,并随后确定候选基因。此外,通过这些方法鉴定的基因可以使用动物模型进一步进行特征描述和相互作用研究,这在人类中是不可能的。