Locating a blood pressure quantitative trait locus within 117 kb on the rat genome: substitution mapping and renal expression analysis.
Previously, a blood pressure (BP) quantitative trait locus (QTL) on rat chromosome 9 (RNO9) was localized to a <2.4 cM interval using congenic strains generated by introgressing segments of RNO9 from the Dahl salt-resistant (R) rat into the background of the Dahl salt-sensitive (S) rat. Renal gene expression using Affymetrix gene chips was profiled on S and a congenic strain spanning the 2.4-cM BP QTL interval. This analysis identified 20 differentially expressed genes/expressed sequence tags. Of these, the locus with the greatest differential expression (30- to 35-fold) was regulated endocrine-specific protein 18 (Resp18), which also mapped in the 2.4-cM BP QTL interval. Additional substitution mapping located the QTL to <0.4 cM or approximately 493 kb. This newly defined QTL region still included Resp18. Nucleotide variants were identified between S and R genomic DNA of Resp18 in the coding, 5' regulatory and 3' untranslated regions. The coding sequence variation (T/C) occurs in exon 2 and predicts an amino acid change (Ile/Val) in the protein product. Resp18 was considered a differentially expressed positional candidate for the QTL. To fine-map the BP QTL, we constructed a congenic strain with a smaller introgressed region. Compared with the S rat, this strain (1) had significantly lower BP, (2) did not contain the R form of Resp18, and (3) did not retain the rather spectacular differential expression of Resp18. Together, these results demonstrate that a BP QTL independent of Resp18 exists within the newly defined 117-kb QTL region on RNO9.
Garrett
Michael R
MR
Department of Physiology and Cardiovascular Genomics, Medical College of Ohio, Toledo 43614-5804, USA.
Meng
Haijin
H
Rapp
John P
JP
Joe
Bina
B
D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D015870:Gene Expression; D020869:Gene Expression Profiling; D016678:Genome; D007668:Kidney / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D051381:Rats; D020303:Rats, Inbred Dahl; D011919:Rats, Inbred Strains; D013045:Species Specificity
D009419:Nerve Tissue Proteins; C086381:regulated endocrine secretory protein 18