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Unraveling the genetics of chronic kidney disease using animal models.

机译:使用动物模型阐明慢性肾脏疾病的遗传学。

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Identifying genes underlying common forms of kidney disease in humans has proven difficult, expensive, and time consuming. Quantitative trait loci (QTL) for several complex traits are concordant among mice, rats, and humans, suggesting that genetic findings from these animal models are relevant to human disease. Therefore, we reviewed the literature on genetic studies of kidney disease in rat and mouse and examined the concordance between kidney disease QTL across species. Fifteen genomic regions contribute to kidney disease in the rat, with 12 replicated either in a separate rat cross or in another species. Five loci found in humans were concordant to QTL found in the rat. Two of these were found by homology to a previously identified rat QTL on chromosome 1, demonstrating that kidney disease loci in animal models can predict the location of kidney disease loci in humans. In contrast to the rat, the mouse has been underutilized in the genetic analysis of polygenic kidney disease, although mutagenesis and QTL analysis in the mouse are likely to contribute new findings in the near future. Knowledge of kidney disease loci conserved between the mouse and rat will identify prime candidate loci to test for association with chronic kidney disease in humans.
机译:事实证明,鉴定人类肾脏疾病常见形式的基础基因困难,昂贵且耗时。几种复杂性状的数量性状基因座(QTL)在小鼠,大鼠和人类之间是一致的,这表明来自这些动物模型的遗传发现与人类疾病有关。因此,我们回顾了关于大鼠和小鼠肾脏疾病遗传研究的文献,并研究了跨物种的肾脏疾病QTL之间的一致性。 15个基因组区域导致了大鼠肾脏疾病,其中12个在单独的大鼠杂交中或在其他物种中复制。在人类中发现的五个基因座与在大鼠中发现的QTL相一致。其中两个是通过与先前在1号染色体上鉴定出的大鼠QTL同源性发现的,表明动物模型中的肾脏疾病基因座可以预测人类中肾脏疾病基因座的位置。与大鼠相反,尽管在不久的将来,小鼠的诱变和QTL分析很可能会带来新的发现,但在多基因肾病的遗传分析中,小鼠的利用不足。小鼠和大鼠之间保守的肾脏疾病基因座的知识将确定主要的候选基因座,以测试与人类慢性肾脏疾病的关联。

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