RGD Reference Report - Locating a Blood Pressure Quantitative Trait Locus Within 117 kb on the Rat Genome. Substitution Mapping and Renal Expression Analysis. - Rat Genome Database

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Locating a Blood Pressure Quantitative Trait Locus Within 117 kb on the Rat Genome. Substitution Mapping and Renal Expression Analysis.

Authors: Garrett, MR  Meng, H  Rapp, JP  Joe, B 
Citation: Garrett MR, etal., Hypertension 2005 Jan 17;.
RGD ID: 1334447
Pubmed: PMID:15655120   (View Abstract at PubMed)
DOI: DOI:10.1161/01.HYP.0000154678.64340.7f   (Journal Full-text)

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.



Objects Annotated

QTLs
Bp284  (Blood pressure QTL 284)

Objects referenced in this article
Marker D9Wox31 D9Wox31 Rattus norvegicus
Marker D9Mco43 D9Mco43 Rattus norvegicus
Marker D9Mco14 D9Mco14 Rattus norvegicus
Strain SS.SR-(D9Mco61-D9Mco27)/Mco null Rattus norvegicus
Strain SS.SR-(D9Mgh11-D9Mco33)/Mco null Rattus norvegicus
Strain SS.SR-(D9Rat89-D9Mco27)/Mco null Rattus norvegicus
Strain SS.SR-(D9Rat89-Resp18)/Mco null Rattus norvegicus

Additional Information