Identification Of Candidate Genes For Hypertension In Congenic Strain For Rat Chromossome 2

Using a genome-wide scan approach, we have previously mapped a QTL on chromosomes 2 that influences blood pressure (BP) associated to salt loading in a SHR x Brown Norway (BN) intercross. A rat congenic strain harbouring a 28.5 cM BN chromossomal interval was developed using a backcross marker assisted breeding schedule. Basal blood pressure was significantly reduced in the congenic strain compared to the parental SHR (187.3 ± 2.3 vs. 167.7 ± 2.0* mmHg, p<0.05). To test the hypothesis that genes contained within this interval show different pattern of kidney expression, a chromosomal walking strategy was established to identify the total number of genes within the chromosomal 2 interval and the ones that show renal expression. Using renal ESTs from public databases and 120K SAGE generated tags, 512 known and unknown genes were annotated. Of those, 49 were expressed in the kidney and were evaluated by real time RT-PCR in kidney samples from congenic (N=8) VS. SHR (N=8) rats. We identified 15 genes fulfilling the criteria within the region of interest: LOC 295235, Syt11, Tpm3, S100a10, LOC310681, Vdup1, Hmgcs2, Hao3, Unr, Slipr, Slc16a1, Cd53, Gstm1, Col11a1, LOC295394. Taken together, these data provide direct evidence that a mapped QTL on chromosome 2 indeed influences BP phenotype on the SHR. Furthermore, a genetic strategy based on the differential pattern of kidney expression successfully identified 15 genes to be further investigated regarding their potencial to directly influence blood pressure in vivo.