BN phenome: detailed characterization of the cardiovascular, renal, and pulmonary systems of the sequenced rat.
The postgenome era has provided resources to link disease phenotypes to the genomic sequence, i.e., creating a disease "phenome." Our detailed characterization of the sequenced BN rat strain (BN/NHsdMcwi) provides the first concerted effort in creating a direct link between a sequenced genome and its resulting biology. For the BN sequence to be of broad value to investigators, these measures need to be put into the context of the spectrum of the laboratory rats, so that their physiology can be benchmarked against the sequenced BN. As a major step in generating a comprehensive cardiovascular and pulmonary disease phenome, we measured 281 traits related to diseases of the heart, lung, and blood (http://pga.mcw.edu) in the sequenced BN. We compared these data with those of the same traits measured across multiple genetic backgrounds, both genders, and differing environments. We show that no single strain, inbred or outbred, can be considered a physiological control strain; what is normal depends on what trait is being measured and the strains' genome backgrounds. We find vast differences between the genders, also dependent on genome background. By combining the values across all strains studied, we generated a "population" mean and normal range of values for each of these traits, which are more genetically representative than the measured values in any single inbred or outbred strain. These data provide a baseline for physiological comparison of traits related to cardiovascular, lung, blood, and renal function in the sequenced BN rats relative to the major strains of rats studied in biomedical research.
Kwitek
Anne E
AE
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. akwitek@mcw.edu
Jacob
Howard J
HJ
Baker
John E
JE
Dwinell
Melinda R
MR
Forster
Hubert V
HV
Greene
Andrew S
AS
Kunert
Mary Pat
MP
Lombard
Julian H
JH
Mattson
David L
DL
Pritchard
Kirkwood A
KA
Roman
Richard J
RJ
Tonellato
Peter J
PJ
Cowley
Allen W
AW
D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D014644:Genetic Variation; D016678:Genome; D006402:Hematologic Diseases / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics*; D008171:Lung Diseases / Q000235:genetics*; D008297:Male; D010641:Phenotype; D051381:Rats; D011914:Rats, Inbred BN / Q000235:genetics*; D012737:Sex Factors; D013045:Species Specificity