Genetic analysis of blood pressure in 8 mouse intercross populations.
Genetic analysis of blood pressure in 8 mouse intercross populations.
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DOI：
10.1161/hypertensionaha.109.134569
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发表时间：
2009-10
期刊：
影响因子：
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通讯作者：
DiPetrillo K
中科院分区：
文献类型：
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作者：
Feng M;Deerhake ME;Keating R;Thaisz J;Xu L;Tsaih SW;Smith R;Ishige T;Sugiyama F;Churchill GA;DiPetrillo K
高血压的遗传基础已经很好地建立起来，但很少有导致常见形式高血压的基因是已知的。啮齿动物模型中的数量性状基因座（QTL）分析可以指导人类高血压基因的搜索，但在这方面，小鼠的优良遗传资源尚未得到充分利用。为了解决这个问题，我们调查了来自37个近交系的小鼠的血压变化，并在8个杂交群体中产生了2，577只小鼠，以进行血压的QTL分析。我们在这些群体中鉴定了14个血压QTL，包括至少7个先前与血压无关的小鼠基因组区域。在我们的研究或以前发表的研究中，在多个杂交中检测到许多QTL，这有助于使用生物信息学方法来缩小QTL范围并集中寻找候选基因。人类基因组中对应于小鼠14个血压QTL中除一个以外的所有区域都与人类血压相关，这表明这些区域包含在血压控制中具有保守作用的致病基因。这些结果极大地扩展了我们对小鼠血压调节基因组区域的了解，并支持未来的研究，以确定这些QTL间隔内的致病基因。
The genetic basis of hypertension is well established, yet very few genes that cause common forms of hypertension are known. Quantitative trait locus (QTL) analyses in rodent models can guide the search for human hypertension genes, but the excellent genetic resources for mice have been underutilized in this regard. To address this issue, we surveyed blood pressure variation in mice from 37 inbred strains and generated 2,577 mice in eight intercross populations to perform QTL analyses of blood pressure. We identified 14 blood pressure QTL in these populations, including at least 7 regions of the mouse genome not previously linked to blood pressure. Many QTL were detected in multiple crosses, either within our study or in previously published studies, which facilitates the use of bioinformatics methods to narrow the QTL and focus the search for candidate genes. The regions of the human genome that correspond to all but one of the 14 blood pressure QTL in mice are linked to blood pressure in humans, suggesting that these regions contain causal genes with a conserved role in blood pressure control. These results greatly expand our knowledge of the genomic regions underlying blood pressure regulation in mice and support future studies to identify the causal genes within these QTL intervals.