Closely linked non-additive blood pressure quantitative trait loci.
Closely linked non-additive blood pressure quantitative trait loci.
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紧密连锁的非加性血压数量性状基因座。
DOI：
10.1007/s00335-008-9093-1
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Joe,Bina
中科院分区：
文献类型：
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作者：
Toland,EdwardJ;Saad,Yasser;Yerga-Woolwine,Shane;Ummel,Steven;Farms,Phyllis;Ramdath,Ramona;Frank,BryanC;Lee,NormanH;Joe,Bina
通过连锁和替代作图有足够的证据表明大鼠1号染色体含有多个血压（BP）数量性状基因座（QTL）。其中，BP QTL1b 是我们实验室先前报道的，使用的是通过将 LEW 大鼠的正常血压等位基因渗入高血压 Dahl 盐敏感 (S) 大鼠的遗传背景而衍生的同源品系。 QTL1b 跨越的区域相当大 (20.92 Mb)，因此需要以更高的分辨率进一步作图，以便于系统地识别潜在的遗传决定因素。在 Dahl 盐敏感 (S) 大鼠背景上使用含有 LEW 大鼠染色体片段的同源品系，构建并表征了同源亚品系的进一步迭代。从同源亚系的这一新迭代中获得的集体数据为 QTL1b 的进一步片段化和分辨率的提高提供了证据。 QTL1b 至少有两个独立的血压遗传决定因素。它们位于 7.40 Mb 和 7.31 Mb 范围内，分别称为 QTL1b1 区域和 QTL1b2 区域。在两个 BP QTL 之间检测到遗传相互作用。有趣的是，先前报道的位于新定位的 QTL1b1 区域内的差异表达基因中有 5 个仍然存在差异表达。同源菌株S.LEW（D1Mco36-D1Mco101）仅包含QTL1b1区域，但不包含QTL1b2区域，可作为进一步剖析QTL1b1区域和验证Nr2f2作为位置候选基因的遗传工具。总体而言，这项研究代表了识别控制血压的遗传因素的中间但必然的进展。
There is enough evidence through linkage and substitution mapping to indicate that rat chromosome 1 harbors multiple blood pressure (BP) quantitative trait loci (QTLs). Of these, BP QTL1b was previously reported from our laboratory using congenic strains derived by introgressing normotensive alleles from the LEW rat onto the genetic background of the hypertensive Dahl salt-sensitive (S) rat. The region spanned by QTL1b is quite large (20.92 Mb), thus requiring further mapping with improved resolution so as to facilitate systematic identification of the underlying genetic determinant(s). Using congenic strains containing the LEW rat chromosomal segments on the Dahl salt-sensitive (S) rat background, further iterations of congenic substrains were constructed and characterized. Collective data obtained from this new iteration of congenic substrains provided evidence for further fragmentation of QTL1b with improved resolution. At least two separate genetic determinants of blood pressure underlie QTL1b. These are within 7.40 Mb and 7.31 Mb and are known as the QTL1b1 region and the QTL1b2 region, respectively. A genetic interaction was detected between the two BP QTLs. Interestingly, five of the previously reported differentially expressed genes located within the newly mapped QTL1b1 region remained differentially expressed. The congenic strain S.LEW(D1Mco36-D1Mco101), which harbors the QTL1b1 region alone but not the QTL1b2 region, serves as a genetic tool for further dissection of the QTL1b1 region and validation ofNr2f2as a positional candidate gene. Overall, this study represents an intermediary yet obligatory progression towards the identification of genetic elements controlling BP.