Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease.
Integration of genome-wide expression profiling with linkage analysis is a new approach to identifying genes underlying complex traits. We applied this approach to the regulation of gene expression in the BXH/HXB panel of rat recombinant inbred strains, one of the largest available rodent recombinant inbred panels and a leading resource for genetic analysis of the highly prevalent metabolic syndrome. In two tissues important to the pathogenesis of the metabolic syndrome, we mapped cis- and trans-regulatory control elements for expression of thousands of genes across the genome. Many of the most highly linked expression quantitative trait loci are regulated in cis, are inherited essentially as monogenic traits and are good candidate genes for previously mapped physiological quantitative trait loci in the rat. By comparative mapping we generated a data set of 73 candidate genes for hypertension that merit testing in human populations. Mining of this publicly available data set is expected to lead to new insights into the genes and regulatory pathways underlying the extensive range of metabolic and cardiovascular disease phenotypes that segregate in these recombinant inbred strains.
Hubner
Norbert
N
Max-Delbrück-Center for Molecular Medicine, Berlin-Buch 13125, Germany.
Wallace
Caroline A
CA
Zimdahl
Heike
H
Petretto
Enrico
E
Schulz
Herbert
H
Maciver
Fiona
F
Mueller
Michael
M
Hummel
Oliver
O
Monti
Jan
J
Zidek
Vaclav
V
Musilova
Alena
A
Kren
Vladimir
V
Causton
Helen
H
Game
Laurence
L
Born
Gabriele
G
Schmidt
Sabine
S
Müller
Anita
A
Cook
Stuart A
SA
Kurtz
Theodore W
TW
Whittaker
John
J
Pravenec
Michal
M
Aitman
Timothy J
TJ
D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D020869:Gene Expression Profiling; D008040:Genetic Linkage; D040641:Quantitative Trait Loci; D051381:Rats; D011995:Recombination, Genetic; D014158:Transcription, Genetic