Toland Edward J, Saad Yasser, Yerga-Woolwine Shane, Ummel Steven, Farms Phyllis, Ramdath Ramona, Frank Bryan C, Lee Norman H, Joe Bina
Physiological Genomics Laboratory, Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3035 Arlington Avenue, Toledo, OH 43614, USA.
Mamm Genome. 2008 Mar;19(3):209-18. doi: 10.1007/s00335-008-9093-1. Epub 2008 Mar 7.
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 of Nr2f2 as a positional candidate gene. Overall, this study represents an intermediary yet obligatory progression towards the identification of genetic elements controlling BP.
通过连锁和置换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先前已由我们实验室报道，该QTL是通过将来自LEW大鼠的正常血压等位基因渗入高血压Dahl盐敏感（S）大鼠的遗传背景而获得的近交系。QTL1b跨越的区域相当大（20.92 Mb），因此需要进一步以更高分辨率进行定位，以便于系统鉴定潜在的遗传决定因素。利用在Dahl盐敏感（S）大鼠背景上含有LEW大鼠染色体片段的近交系，构建并鉴定了近交亚系的进一步迭代。从近交亚系的这一新迭代中获得的总体数据为QTL1b以更高分辨率进一步细分提供了证据。至少有两个独立的血压遗传决定因素是QTL1b的基础。它们分别位于7.40 Mb和7.31 Mb范围内，分别被称为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区域内的五个差异表达基因仍然差异表达。仅含有QTL1b1区域而不含有QTL1b2区域的近交系S.LEW（D1Mco36-D1Mco101），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，这项研究代表了朝着鉴定控制血压的遗传元件迈出的中间但必不可少的一步。
