Conserved synteny in rat and mouse for a blood pressure QTL on human chromosome 17.
Evidence for blood pressure quantitative trait loci (QTLs) on rat chromosome 10 has been found in multiple independent studies. Analysis of the homologous region on human chromosome 17 revealed significant linkage to blood pressure. The critical segment on human chromosome 17 spans a large interval containing the genes Itga2b, Gfap, and Itgb3. Therefore, findings in the rat may help to refine the position of blood pressure-regulating loci, assuming a common molecular cause across species. However, it has recently been suggested that the gene order in human, rat, and mouse is not conserved in this region, leaving uncertainty about the overlap of the blood pressure- regulating region between human chromosome 17 and rat chromosome 10. We have performed a detailed comparative analysis among human, mouse, and rat, defining the segment in question, by obtaining gene structure information in silico and by radiation hybrid mapping. It is of interest that this region also contains Wnk4, a gene previously identified to cause pseudohypoaldosteronism type II and human hypertension. Our results definitively show that the conserved synteny extends among human chromosome 17, rat chromosome 10, and mouse chromosome 11, demonstrating an overlap between previously localized blood pressure QTLs in humans and rats.
Zimdahl
Heike
H
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Kreitler
Thomas
T
Gösele
Claudia
C
Ganten
Detlev
D
Hübner
Norbert
N
D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D019655:Quantitative Trait, Heritable; D021101:Radiation Hybrid Mapping; D051381:Rats; D026801:Synteny
C499024:Prkwnk4 protein, mouse; C499025:Wnk4 protein, rat; D017346:Protein Serine-Threonine Kinases; C433806:WNK4 protein, human