Identifying Chromosome 3 Blood Pressure QTL Candidates

点击翻译按钮获取中文摘要

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