Individual QTLs controlling quantitative variation in blood pressure inherited in a Mendelian mode.
We studied three possible genotypes at 10 well-defined blood pressure (BP) QTLs using congenic rat lines. The central question was whether the hypertensive or normotensive allele is dominant, or whether there is partial dominance. The congenic strains were employed to investigate the BP effects of alleles originating from normotensive rats in the background of hypertensive Dahl salt-sensitive (DSS) rats. The normotensive alleles at eight QTLs were fully dominant over DSS alleles, which we tentatively interpreted as indicating that DSS rats incurred a loss of function at these loci and that the QTLs produced BP-reducing agents. In contrast, the normotensive allele of only one QTL was recessive over its DSS counterpart, implying a gain of function at this QTL or a null allele involved in generating a BP-elevating agent. Only one locus, C17QTL, had alleles exhibiting partial dominance. These estimates of dominance differ considerably from those obtained by QTL analysis in a F2 cross. This disagreement demonstrates the importance of establishing a cause-effect relationship between a QTL and its phenotypic effect via congenic strains. The dominance relationships suggest pertinent strategies for gene identification and pharmaceutical intervention.
Duong
C
C
Department of Medicine, Research Centre, Centre hospitalier de l'Université de Montréal (CHUM)-Technopôle Angus, 2901 Rachel Street East, Montréal, Québec, Canada.
Charron
S
S
Deng
Y
Y
Xiao
C
C
Ménard
A
A
Roy
J
J
Deng
A Y
AY
D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D018628:Gene Dosage; D005799:Genes, Dominant; D006579:Heterozygote; D006720:Homozygote; D006824:Hybridization, Genetic; D008297:Male; D020412:Multifactorial Inheritance; D040641:Quantitative Trait Loci; D051381:Rats; D020303:Rats, Inbred Dahl; D011917:Rats, Inbred Lew