Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, and Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
J Hypertens. 2018 Jul;36(7):1486-1491. doi: 10.1097/HJH.0000000000001732.
Previously, using linkage analysis and substitution mapping, two closely-linked interactive blood pressure quantitative trait loci (QTLs), BP QTL1 and BP QTL2, were located within a 13.96 Mb region from 117894038 to 131853815 bp (RGSC 3.4 version) on rat chromosome 5 (RNO5). This was done by using a series of congenic strains consisting of genomic segments of the Dahl salt-sensitive (S) rat substituted with that of the normotensive Lewis (LEW) rat. The interactive nature of the two loci was further confirmed by the construction and characterization of a panel of S.LEW bicongenic strains and corresponding S.LEW monocongenic strains, which provided definitive evidence of epistasis (genetic interaction) between BP QTL1 (7.77 Mb) and BP QTL2 (4.18 Mb). The purpose of this work was to further map these interacting QTLs.
A new panel of seven new S.LEW bicongenic strains was constructed and characterized for BP.
The data obtained from these new strains further resolved BP QTL1 from 7.77 to 2.93 Mb. Further, BP QTL2 was traceable as not being a single QTL, but a composite of at least three QTLs, LEW alleles at two of which located within 2.26 Mb and 175 kb lowered BP but the third one located within 1.31 Mb increased BP.
Lack of coding variation within any of the regions further mapped within the previous QTL2 suggests noncoding variation as likely responsible for the observed epistasis.
先前，通过连锁分析和替换作图，将两个紧密连锁的血压数量性状基因座（QTL），BP QTL1 和 BP QTL2，定位在大鼠 5 号染色体（RNO5）117894038 到 131853815 bp（RGSC 3.4 版本）之间的 13.96 Mb 区域内。这是通过使用一系列由盐敏感（S）大鼠基因组片段与正常血压的刘易斯（LEW）大鼠基因组片段替换而成的近交系完成的。两个基因座的相互作用性质通过构建和鉴定一组 S.LEW 双近交系和相应的 S.LEW 单近交系进一步得到证实，这为 BP QTL1（7.77 Mb）和 BP QTL2（4.18 Mb）之间的上位性（遗传相互作用）提供了明确的证据。这项工作的目的是进一步对这些相互作用的 QTL 进行定位。
构建并鉴定了一组新的七个 S.LEW 双近交系用于 BP。
从这些新的近交系中获得的数据进一步将 BP QTL1 从 7.77 到 2.93 Mb 进行了定位。此外，BP QTL2 并不是单个 QTL，而是至少三个 QTL 的组合，其中两个 LEW 等位基因位于 2.26 Mb 和 175 kb 内，降低血压，但第三个位于 1.31 Mb 内，升高血压。
在先前的 QTL2 内进一步定位的任何区域内缺乏编码变异表明，非编码变异可能是观察到的上位性的原因。
