Genetic analysis of blood pressure in C3H/HeJ and SWR/J mice.
Hypertension is a complex phenotype induced by multiple environmental and genetic factors. Quantitative trait locus (QTL) analysis is a powerful method for identifying genomic regions underlying complex diseases. We conducted a QTL analysis of blood pressure in mice using 217 F(2) progeny (males and females) from a cross between the normotensive C3H/HeJ and hypertensive SWR/J inbred strains. Our analysis identified significant QTL controlling blood pressure on chromosome 1 [Chr 1; Bpq8; peak 78 cM; 95% confidence interval 64-106 cM; logarithm of the odds ratio (LOD) 3.5; peak marker D1Mit105] and on Chr 16 (Bpq9; peak 56 cM; 95% confidence interval 46-58 cM; LOD 3.6; peak marker D16Mit158). Bpq8 was previously identified in a cross between C57BL/6J and A/J mice, and we narrowed this QTL from 42 to 18 cM (95% confidence interval 68-86 cM) by combining the data from these crosses. By examining Bpq8 for regions where ancestral alleles were conserved among the high allele strains (C57BL/6J, SWR/J) and different from the low allele strains (A/J, C3H/HeJ), we identified a 2.3-cM region where the high allele strains shared a common haplotype. Bpq8 is concordant with known QTL in both rat and human, suggesting that the causal gene underlying Bpq8 may be conserved as a disease gene in human hypertension.
The Jackson Laboratory, Bar Harbor, Maine 04609, USA. kjd@jax.org
Keith
K
DiPetrillo
Shirng-Wern
SW
Tsaih
Susan
S
Sheehan
Conrado
C
Johns
Peter
P
Kelmenson
Haralambos
H
Gavras
Gary A
GA
Churchill
Beverly
B
Paigen
D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D005260:Female; D006239:Haplotypes; D006339:Heart Rate / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci; D012737:Sex Factors