Genomic map of cardiovascular phenotypes of hypertension in female Dahl S rats. Physiol Genomics 2003 Nov 11;15(3):243-57
Date
10/09/2003Pubmed ID
14532335DOI
10.1152/physiolgenomics.00105.2003Scopus ID
2-s2.0-20244376857 (requires institutional sign-in at Scopus site) 87 CitationsAbstract
Genetic linkage analyses in human populations have traditionally combined male and female progeny for determination of quantitative trait loci (QTL). In contrast, most rodent studies have focused primarily on males. This study represents an extensive female-specific linkage analysis in which 236 neuroendocrine, renal, and cardiovascular traits related to arterial pressure (BP) were determined in 99 female F2 rats derived from a cross of Dahl salt-sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/SsNHsdMcwi (BN) rats. We identified 126 QTL for 96 traits on 19 of the 20 autosomal chromosomes of the female progeny. Four chromosomes (3, 6, 7, and 11) were identified as especially important in regulation of arterial pressure and renal function, since aggregates of 8-11 QTL mapped together on these chromosomes. BP QTL in this female population differed considerably from those previously found in male, other female, or mixed sex population linkage analysis studies using SS rats. Kidney weight divided by body weight was identified as an intermediate phenotype that mapped to the same region of the genome as resting diastolic blood pressure and was correlated with that same BP phenotype. Seven other phenotypes were considered as "potential intermediate phenotypes, " which mapped to the same region of the genome as a BP QTL but were not correlated with BP. These included renal vascular responses to ANG II and ACh and indices of baroreceptor responsiveness. Secondary traits were also identified that were likely to be consequences of hypertension (correlated with BP but not mapped to a BP QTL). Seven such traits were found, notably heart rate, plasma cholesterol, and renal glomerular injury. The development of a female rat systems biology map of cardiovascular function represents the first attempt to prioritize those regions of the genome important for development of hypertension and end organ damage in female rats.
Author List
Moreno C, Dumas P, Kaldunski ML, Tonellato PJ, Greene AS, Roman RJ, Cheng Q, Wang Z, Jacob HJ, Cowley AW JrAuthor
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Cardiovascular Diseases
Chromosome Mapping
Crosses, Genetic
Female
Genetic Linkage
Genome
Hypertension
Male
Phenotype
Quantitative Trait Loci
Rats
Rats, Inbred BN
Rats, Inbred Dahl
