Identifying Chromosome 3 Blood Pressure QTL Candidates

超出提供的空间。我们的长期目标是识别使动物对血压敏感或耐盐的基因，最终目的是将这一知识应用于阐明影响人类血压的因素。我们以前在大鼠3号染色体(RNO_3)上发现了两个与血压有关的基因座，这些基因座来自近交系的S大鼠和耐盐(R)大鼠。其中一个血压数量性状基因座位于RNO_3的Q端附近，是通过培育一个同源品系而获得的。从S R-Edn3衍生的R-Edn3同源亚系表明，在RNO_3的Q端至少存在两个不同的BP QTL，并将含有QTL的区域划分为3.3 cM间隔。我们建议更好地定义这个QTL的范围，这有助于识别控制这个BP-QTL的基因(S)。我们推测，泰泽至少有三个不同的BP/心脏质量QTL存在于RNO_3上，S R-Edn3同源基因1at对两个不同的RNO_3 BP QTL具有低的BP等位基因，这部分是由于R-大鼠衍生基因(S)在该区域的表达差异所致在观察到该基因株血压下降后，我们的具体目标是：1)培育S R-Edn3来源的同源菌株，在R-大鼠来源的RNO_3的较小部分携带BP QTL，并最终将该区域切割至10 cm；2)培育“捕捉”D3Wo_c3附近RNO_3上的第三个BP QTL的同源菌株，该QTL位于Q端附近的两个BP QTL之间，距离90 cM以上；3)利用细菌“人工染色体”和P_1在顶端簇体的重叠群，对RNO_3区域进行详细的遗传、比较和物理定位；4)寻找RNO3bpQTL的强候选基因，位于QTL区内的基因将被作为候选基因。我们还将利用cDNA微阵列杂交技术鉴定在同源亚株S中差异表达的基因，与同源的S株相比，定位在QTL区的差异表达基因(在特定的目标1中鉴定)将是该特定血压QTL执行位点========================================Section End===========================================的优势候选基因。

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===========================================