Congenic Mapping and Sequence Analysis of the Renin Locus
Congenic Mapping and Sequence Analysis of the Renin Locus
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DOI：
10.1161/hypertensionaha.111.01008
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发表时间：
2013-04-01
期刊：
影响因子：
8.3
通讯作者：
Moreno, Carol
中科院分区：
文献类型：
--
作者：
Flister, Michael J.;Hoffman, Matthew J.;Moreno, Carol
肾素是第一个通过连锁分析绘制的大鼠血压（BP）数量性状基因座。随后捕获肾素区域不同部分的 BP 连锁和同类研究得出了相互矛盾的结果，表明多个相互依赖的 BP 位点可能存在于包括肾素的 13 号染色体 BP 数量性状位点中。我们使用 SS-13BN 同源菌株来绘制肾素区域的 2 个 BP 位点 (chr13: 45.2-49.0 Mb)。我们在肾素 (chr13: 46.1-47.2 Mb) 周围发现了一个 1.1-Mb 的棕色挪威保护区域，它使血压显着降低了 32 mm Hg。肾素保护性血压位点被相邻的高血压位点 (chr13: 47.2-49.0 Mb) 抵消，使血压显着升高 29 mm Hg。对保护性和高血压性血压基因座的序列分析显示，Dahl 盐敏感/Mcwi 大鼠和 Brown挪威大鼠之间分别存在 1433 个和 2063 个变异。为了进一步减少候选变体列表，我们对具有先前报道的 BP 表型的重叠 SS-13(SR) 同源菌株 (S/ren(rr)) 进行了重新基因分型。 Dahl 盐敏感型、Dahl R 和 Brown Bulgaria 之间的序列比较将 2 个 BP 位点中的候选变异数量减少了 42%，有待进一步研究。结合之前的研究，这些数据表明至少有 4 个 BP 基因座位于 30-cM 13 号染色体 BP 数量性状基因座内，其中包括肾素。 （高血压。2013；61：850-856。）圈在线数据补充
Renin was the first blood pressure (BP) quantitative trait locus mapped by linkage analysis in the rat. Subsequent BP linkage and congenic studies capturing different portions of the renin region have returned conflicting results, suggesting that multiple interdependent BP loci may be residing in the chromosome 13 BP quantitative trait locus that includes Renin. We used SS-13BN congenic strains to map 2 BP loci in the Renin region (chr13: 45.2-49.0 Mb). We identified a 1.1-Mb protective Brown Norway region around Renin (chr13: 46.1-47.2 Mb) that significantly decreased BP by 32 mm Hg. The Renin protective BP locus was offset by an adjacent hypertensive locus (chr13: 47.2-49.0 Mb) that significantly increased BP by 29 mm Hg. Sequence analysis of the protective and hypertensive BP loci revealed 1433 and 2063 variants between Dahl salt-sensitive/Mcwi and Brown Norway rats, respectively. To further reduce the list of candidate variants, we regenotyped an overlapping SS-13(SR) congenic strain (S/ren(rr)) with a previously reported BP phenotype. Sequence comparison among Dahl salt-sensitive, Dahl R, and Brown Norway reduced the number of candidate variants in the 2 BP loci by 42% for further study. Combined with previous studies, these data suggest that at least 4 BP loci reside within the 30-cM chromosome 13 BP quantitative trait locus that includes Renin. (Hypertension. 2013;61:850-856.) circle Online Data Supplement