Genetic analysis of blood pressure in 8 mouse intercross populations.
The genetic basis of hypertension is well established, yet very few genes that cause common forms of hypertension are known. Quantitative trait locus (QTL) analyses in rodent models can guide the search for human hypertension genes, but the excellent genetic resources for mice have been underused in this regard. To address this issue, we surveyed blood pressure variation in mice from 37 inbred strains and generated 2577 mice in 8 intercross populations to perform QTL analyses of blood pressure. We identified 14 blood pressure QTL in these populations, including > or =7 regions of the mouse genome not linked previously to blood pressure. Many QTL were detected in multiple crosses, either within our study or in studies published previously, which facilitates the use of bioinformatics methods to narrow the QTL and focus the search for candidate genes. The regions of the human genome that correspond to all but 1 of the 14 blood pressure QTL in mice are linked to blood pressure in humans, suggesting that these regions contain causal genes with a conserved role in blood pressure control. These results greatly expand our knowledge of the genomic regions underlying blood pressure regulation in mice and support future studies to identify the causal genes within these QTL intervals.
Feng
Minjie
M
Novartis Institute for BioMedical Research, 1 Health Plaza, East Hanover, NJ 07936, USA.
Deerhake
Marion E
ME
Keating
Ryan
R
Thaisz
Jill
J
Xu
Lingfei
L
Tsaih
Shirng-Wern
SW
Smith
Randy
R
Ishige
Taiichiro
T
Sugiyama
Fumihiro
F
Churchill
Gary A
GA
DiPetrillo
Keith
K
D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006973:Hypertension / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*