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Genes revealed by Bayesian graphical model analysis in pathways mediating hypertension are differentially expressed in the renal medulla of Dahl salt‐sensitive rats (912.6)
Author(s) -
Evans Louise,
Peterson Christine,
Stingo Francesco,
Woo Ahn Kwang,
Liu Pengyuan,
Vannucci Marina,
Laud Purushottam,
Yang Chun,
Liang Mingyu,
Cowley Allen
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.912.6
Subject(s) - gene , candidate gene , biology , congenic , endocrinology , medicine , microbiology and biotechnology , chemistry , genetics
A 1.37Mbp region of the Brown Norway rat Chr13 confers protection from salt‐sensitivity to Dahl salt‐sensitive (SS) rats. Of five candidate genes identified in this region, only Rfwd2 was highly expressed in the renal medulla. A pathway‐based Bayesian graphical model analysis utilizing RNA‐seq and GeneChip data was used to identify relationships between Rfwd2 and genes in pathways related to blood pressure. GeneChip data was used to assess whether the genes with a high marginal posterior probability of interdependence with Rfwd2 were differentially expressed in the renal medulla of SS vs. salt‐resistant congenic SS.13BN26 rats fed 0.4% (LS) or 4% NaCl (HS) diet for 7‐days. Of the 9 genes with the highest absolute partial correlations with Rfwd2, 4 were quantifiable by GeneChip analysis and significantly different (P<0.05) between SS and SS.13BN26 rats: F8 (Factor VIII) (lower in SS on LS/HS); Csnk1d (Casein kinase 1 delta) (higher in SS rats on LS/HS); Pik3ca (Phosphatidylinositol‐4,5‐bisphosphate 3‐kinase) (lower in SS rats on LS, suppressed in both on HS diet); Acly (ATP citrate lyase) (increased with HS in both). These analyses have allowed the unbiased identification of genes associated with our candidate gene providing new insights into salt‐sensitivity.