Identifying Chromosome 3 Blood Pressure QTL Candidates

鉴定 3 号染色体血压 QTL 候选者

• 批准号: 6821351
• 负责人: GEORGE T CICILA
• 金额: $ 29.4万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-16 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6821351
• 关键词: angiotensin /renin /aldosterone hypertension; animal breeding; essential hypertension; genetic mapping; genetic strain; genetic susceptibility; hypertension; inbreeding; laboratory rat; microarray technology; quantitative trait loci

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

超出所提供的空间。我们的长期目标是确定动物对血压盐敏感性或耐盐性的基因，最终目标是将这些知识应用于阐明影响人类血压的因素。我们之前在自交系达尔盐敏感(S)和耐盐(R)大鼠的分离群体中发现了大鼠3号染色体（RNO3）上与血压相关的两个位点。由S R-Edn3衍生而来的S R-Edn3同源亚株表明，RNO3的q端至少存在两个不同的BP qtl，并将含qtl的区域划分为33cm区间。我们假设在RNO3上至少存在三个不同的BP/心脏质量QTL，并且s R-Edn3基因1at携带两个不同的RNO3 BP QTL的低血压等位基因，并且r -大鼠衍生基因在该区域的表达差异在一定程度上导致了该基因菌株观察到的血压降低。1)开发从S R-Edn3衍生的同源菌株，在r -大鼠衍生的RNO3的较小部分携带BP qtl，最终将该区域切至10 cM；2)开发同源菌株“捕获”RNO3上位于D3Wo_c3附近的第三个BP QTL，该QTL距离位于q端附近的两个BP QTL超过90 cM， r -鼠染色体的该区域将被进化为S菌株3)利用细菌人工染色体（BAC）和人工染色体（PAC）上的P1组对含有SPECIFIC AIM 1中鉴定的BP QTL的RNO3区域建立详细的遗传、比较和物理图谱；4)筛选RNO3 BP QTL的强候选基因，筛选含QTL区域内的基因作为候选基因。我们还将筛选congenic substrain_s中与pmental S菌株相比差异表达的基因。通过cDNA阵列杂交技术，定位于QTL-containing区域的差异表达基因（在SPECIFIC AIM 1中鉴定）将成为该特定血压QTL PERFORMANCE SiTE ========================================Section End===========================================的优越候选基因