Feng Minjie, Deerhake Marion E, Keating Ryan, Thaisz Jill, Xu Lingfei, Tsaih Shirng-Wern, Smith Randy, Ishige Taiichiro, Sugiyama Fumihiro, Churchill Gary A, DiPetrillo Keith
Novartis Institute for BioMedical Research, 1 Health Plaza, East Hanover, NJ 07936, USA.
Hypertension. 2009 Oct;54(4):802-9. doi: 10.1161/HYPERTENSIONAHA.109.134569. Epub 2009 Aug 3.
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 underused in this regard. To address this issue, we surveyed blood pressure variation in mice from 37 inbred strains and generated 2577 mice in 8 intercross populations to perform QTL analyses of blood pressure. We identified 14 blood pressure QTL in these populations, including > or =7 regions of the mouse genome not linked previously to blood pressure. Many QTL were detected in multiple crosses, either within our study or in studies published previously, 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 1 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.
高血压的遗传基础已得到充分证实,但导致常见类型高血压的基因却知之甚少。啮齿动物模型中的数量性状基因座(QTL)分析有助于寻找人类高血压相关基因,但在这方面,小鼠出色的遗传资源尚未得到充分利用。为解决这一问题,我们调查了37个近交系小鼠的血压变异情况,并在8个杂交群体中培育了2577只小鼠,以进行血压的QTL分析。我们在这些群体中鉴定出14个血压QTL,包括≥7个此前未与血压相关联的小鼠基因组区域。许多QTL在我们的研究或此前发表的研究中的多个杂交组合中都被检测到,这便于使用生物信息学方法来缩小QTL范围,并聚焦于寻找候选基因。小鼠中14个血压QTL中除1个之外的所有QTL在人类基因组中对应的区域都与人类血压相关,这表明这些区域包含在血压调控中具有保守作用的因果基因。这些结果极大地扩展了我们对小鼠血压调控相关基因组区域的认识,并为未来在这些QTL区间内鉴定因果基因的研究提供了支持。