Palijan Ana, Lambert Raphaelle, Dutil Julie, Sivo Zsuzsa, Deng Alan Y
Research Centre-Centre Hospitalier de l'Université de Montréal, Hôtel Dieu, , Montreal, Quebec, Canada.
Hypertension. 2003 Oct;42(4):515-22. doi: 10.1161/01.HYP.0000090096.88509.15. Epub 2003 Aug 25.
Chromosome mapping based on congenic strains can restrict quantitative trait loci (QTLs) for blood pressure (BP) into small intervals that are otherwise indistinguishable in linkage analysis. Also, congenic strains can be created to test a candidate gene to be a BP QTL. Taking full advantage of these features, we produced 10 congenic strains by replacing various segments of chromosome (Chr) 10 of the Dahl salt-sensitive (DSS) rat with those of the Lewis (LEW) rat. These strains were made to systematically cover an entire section of Chr 10. Three of the strains were designed to narrow the intervals that harbor previously mapped QTL1 and QTL2. Two of the strains were designed for the express purpose of testing the QTL candidacy of loci for inducible nitric oxide synthase (Nos2) and angiotensin-converting enzyme (Ace) genes. BPs of these strains were measured by telemetry and compared with those of the DSS rat. Consequently, QTL1 and QTL2 were narrowed to segments of 53.5 and 100.4 centiRays, respectively. A new QTL, QTL3, was found between QTL1 and QTL2. Both Nos2 and Ace have been disqualified as QTLs in the DSS and LEW comparison. Therefore, there are no obvious candidate genes in the segments that harbor these 3 QTLs, which represent genes previously not thought to be involved in BP regulation. These QTLs will likely have an influence on studies of human hypertension because of their homology with the human CHR 17 region in which QTLs for BP have been found.
基于同类系的染色体定位可将血压（BP）的数量性状基因座（QTL）限定在较小区间内，而这些区间在连锁分析中原本是无法区分的。此外，可以构建同类系来检验某个候选基因是否为血压QTL。充分利用这些特性，我们通过用刘易斯（LEW）大鼠的10号染色体（Chr）的各个片段替换 Dahl 盐敏感（DSS）大鼠的10号染色体的相应片段，培育出了10个同类系。构建这些品系是为了系统地覆盖10号染色体的整个区段。其中3个品系旨在缩小包含先前定位的QTL1和QTL2的区间。另外2个品系专门用于检验诱导型一氧化氮合酶（Nos2）基因和血管紧张素转换酶（Ace）基因的基因座作为血压QTL的可能性。通过遥测技术测量这些品系的血压，并与DSS大鼠的血压进行比较。结果，QTL1和QTL2分别被缩小到53.5和100.4厘镭的区段。在QTL1和QTL2之间发现了一个新的QTL，即QTL3。在DSS和LEW的比较中，Nos2和Ace都被排除在血压QTL之外。因此，在包含这3个QTL的区段中没有明显的候选基因，这些基因以前被认为不参与血压调节。由于这些QTL与人类17号染色体区域具有同源性，而在该区域已发现血压QTL，所以它们可能会对人类高血压的研究产生影响。
