Blood pressure QTL in mice

为了研究高血压的遗传控制，我们对盐敏感的C57BL/6J雄性小鼠与正常的a /J自交系小鼠进行了数量性状位点分析，这些小鼠在饲喂含1%盐的水2周后进行了反向回交。对这些小鼠进行全基因组扫描，并结合传统的基于标记的回归和一种新的同步搜索对，发现了6个与盐诱导血压相关的重要数量性状位点，其中两个是相互作用位点。这6个位点命名为Bpq1-6，分别定位于D1Mit334、D1Mit14、D4Mit164、D5Mit31、D6Mit15和D15Mit13，其中5个位点与大鼠高血压基因位点一致，4个位点与人类高血压基因位点一致，提示模式生物的数量性状位点定位可用于指导人类血压基因的寻找。为了更好地了解原发性高血压的遗传基础，我们对207只（BALB/cJ x CBA/CaJ） F(2)雄性小鼠群体进行了QTL分析，以确定调节血压、心率和心脏重量的基因组区域。我们发现了两个位点，15号染色体上的Bpq6（血压定量位点6）（Chr 15；峰值，16 cM； 95%置信区间，0-25 cM）和7号染色体上的Bpq7（峰值，42 cM； 95%置信区间，35-50 cM）与血压显著相关。我们还分别在D2Mt304（峰值，72 cM； 95%置信区间60-80 cM）和D15MM84（峰值，25 cM； 95%置信区间20-35 cM）上发现了两个位点Hrql（心率定量位点1）和Hrq2，它们与心率显著相关。Hrql和DlAfltlO在心率方面存在显著的基因相互作用（峰值为57 cM， 95%可信区间为45-75 cM）；后一个QTL被命名为Hrq3。fae发现心脏重量的显著位点Jfwgl（心脏重量定量位点1）位于D14Mit67（峰值，38cM； 95%置信区间，20-43 cM）。这些QTL基因的鉴定将有助于更好地了解原发性高血压的病因。少

To investigate the genetic control of hypertension, we performed a quantitative trait locus analysis on male mice from a reciprocal backcross between the salt-sensitive C57BL/6J and the normotensive A/J inbred mouse slrains after they were provided with water containing 1% salt for 2 weeks. Genome-wide scans performed on these mice and analyzed with a combination of conventional markerbased regressions and a novel simultaneous search for pairs revealed six significant quantitative trait loci associated with salt-induced blood pressure, two of which were interacting loci. These six loci, named Bpq1-6 for blood pressure quantitative trait loci, mapped to D1Mit334, D1Mit14, D4Mit164, D5Mit31, D6Mit15, and D15Mit13, Furthermore, five of these six loci were concordant with hypertension loci hi rats, and four were concordant with hypertension loci in humans, suggesting that quantitative trait loci mapping in model organisms can be used to guide the search for human blood pressure genes.To be … More tter understand the genetic basis of essential hypertension, we conducted a QTL analysis of a population of 207 (BALB/cJ x CBA/CaJ) F(2) male mice to identity genomic regions that regulate blood pressure, heart rate, and heart weight. We identified two loci, Bpq6 (blood pressure quantitative locus 6) on chromosome 15 (Chr 15 ; peak, 16 cM ; 95% confidence interval, 0-25 cM) and Bpq7 on Chr 7 (peak, 42 cM ; 95% confidence interval, 35-50 cM) that were significantly associated with blood pressure. We also identified two loci, Hrql (heart rate quantitative locus 1) and Hrq2, on D2Mt304 (peak, 72 cM ; 95% confidence interval 60-80 cM) and D15MM84 (peak, 25 cM ; 95% confidence interval 20-35 cM), respectively, that were sigruficantiy associated with heart rate. A significant gene-gene interaction for heart rate was found between Hrql and DlAfltlO (peak, 57 cM ; 95% confidence interval, 45-75 CM) ; the latter QTL was named Hrq3. fae identified a significant locus for heart weight, Jfwgl (heart weight quantitative locus 1), at D14Mit67 (peak, 38cM ; 95% confidence interval, 20-43 cM). Identification of the genes for these QTL should lead to a better understanding of the causes of essential hypertension. Less