Abstract 361: Characterization of a 1,45 Mbp Blood Pressure QTL in Rat Chromosome 13.
We previously showed that transfer of a 13.3 Mb segment of the Brown Norway (BN) rat chromosome 13 (from position 65.9 to 79.21 Mb) into the Dahl salt-sensitive (SS) background attenuates the development of hypertension. In order to narrow the region and identify the causative genes and sequence variants, we created and phenotyped 13 overlapping congenic strains spanning the candidate region. We performed sequence analysis and gene expression analysis by rtPCR and whole-genome RNA-seq on kidneys of the congenic carrying the 13.3 Mb BN segment and the SS rat. Seven strains carrying segments of BN chromosome 13 spanning the region from 73.59 to 75.04 Mb (1.45 Mbp region) were protected from the development of hypertension by at least 20 mmHg. Proteinuria was also markedly reduced in these strains. In contrast, blood pressure was high in the six strains carrying the SS allele in this 1.45 Mb segment. NextGen sequencing of this 1.45 Mbp candidate region, which contained five genes, revealed 2,198 sequence variants between SS and BN. Two of these were nonsynonymous SNPs in Astn1 and one variant was located on miR488. Initial expression analysis of the genes within this region suggests that Astn1 and Rfwd2 are differentially expressed between SS and the protected congenic strain after high salt; Pappa2 was differentially expressed between SS and the congenic carrying the BN allele at both high and low-salt diet. In summary, we have narrowed a region for salt-sensitive hypertension to 1.55 Mbps, containing five candidate genes, each of which may contribute in some way to salt-sensitive hypertension.
- © 2012 by American Heart Association, Inc.