Identifying Chromosome 3 Blood Pressure QTL Candidates

超出所提供的空间。 我们的长期目标是确定使动物易患高血压盐敏感性或耐盐性的基因，最终的目标是将这些知识应用于阐明影响人类血压的因素。我们先前在从近交系Dahl盐敏感（S）和盐抗性（R）大鼠繁殖的分离群体中鉴定了大鼠3号染色体（RNO 3）上与血压相关的两个基因座，其中一个血压（通过构建同源系SR-Edn 3，定位了位于RNO 3 q端附近的一个BP数量性状位点（QTL）。由SR-Edn 3衍生的同源亚系表明，在RNO 3 q端至少存在两个不同的BP QTL，并将QTL的含QTL区域限定在3 3cM的范围内。其将有助于鉴定负责该BP QTL的基因。我们假设，在RNO 3上存在至少三个不同的BP/心脏质量QTL，并且SR-Edn 3同源基因1at携带两个不同的RNO 3 BP QTL的低BP等位基因，并且在该区域中R-大鼠衍生基因的表达差异部分地负责，根据这一同源品系的血压下降的观察结果，我们的具体目标是：1）开发来源于SR-Edn 3的同源sttb品系，其在R-大鼠来源的RNO 3的较小部分中携带BP QTL，并最终将该区域修剪至10 cM; 2）开发“捕获”RNO 3上靠近D3Wo_c3的第三个BP QTL的同类菌株，其定位在距离位于q-末端附近的两个BP QTL超过90 cM的位置。R-大鼠染色体的该区域将被免疫导入S品系3）开发详细的遗传、比较，以及使用细菌人工染色体（BAC）和人工染色体（PAC）上的P1的重叠群，绘制了含有在SPECIFIC AIM 1中鉴定的BP QTL的RNO 3区域的物理图谱; 4）鉴定RNO 3 BP QTL的强候选基因，并且将位于含有QTL的区域内的基因作为候选基因进行评估。我们还将鉴定在同源亚株S中差异表达的基因，与PmentalS株相比，通过使用cDNA阵列杂交技术，定位在含有QTL的区域中的差异表达基因（在特定目的1中鉴定）将是该特定血压QTL性能的上级候选基因。============================

EXCEED THE SPACE PROVIDED. Our long-term goal is to identify genes pre-disposing animals to blood pressure salt-sensitivity or salt-resistance, with the eventual goal of applying this knowledge to elucidating factors influencing blood pressure in humans We previously identified two loci on rat chromosome 3 (RNO3) linked to blood pressure in a segregating population bred from inbred Dahl salt-sensitive (S) and salt-resistant (R) rats One of these blood pressure (BP) quantitative trait loci (QTL), located near the q-terminus of RNO3, was cont_med by developing a congenic strain, S R-Edn3 Congenic substrains derived from S R-Edn3 indicated that at least two distinct BP QTLs are present at the q-terminus of RNO3 and delimited the QTL-containing region to 3 3 cM interval We propose to better define this QTL-containing interval's extent, which x_ill assist in identifying gene(s) responsible for this BP QTL We hypothesize that theze ale at least three distinct BP/cardiac mass QTLs paesent on RNO3 and that the S R-Edn3 congenic 1at carries low BP alleles for two distinct RNO3 BP QTL and that differences in the expression of R-rat derived gene(s) in this region are responsible, in part, fol this congenic strain's observed decreasedblood pressure Our SPECIFIC AIMS are to: 1) develop congenie sttbstrains derived from S R-Edn3, that carry the BP QTLs in smaller portions of the R-rat derived RNO3 and eventually mowing this region to 1 0 cM; 2) develop congenie strains "trapping" the third BP QTL present on RNO3 near D3Wo_c3, which maps over 90 cM away fiom the two BP QTL located near theq-terminus This region of R-rat chromosome will be irmogressed into the S strain 3) develop detailed genetic, comparative, and physical maps of the RNO3 region containing the BP QTL identified in SPECIFIC AIM 1 using contigs of bacterial "artificial chromosomes (BAC) and P1 at tificial cluomosomes (PAC); 4) identify strong candidate genes for the RNO3 BP QTL, and genes located within the QTL-containing regions will be evaluated as candidates We will also identify genes differentially-expressed in congenic substrain_s, compared with the pmental S strain, by using the cDNA array hybridization technique Differentially-expressed genes that map in the QTL-containing region (identified in SPECIFIC AIM 1) will be superior candidate genes for that specific blood pressure QTL PERFORMANCE SiTE ========================================Section End===========================================