title: Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease.
abstract: 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.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin-Buch 13125, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Wallace
authors.forename: Heike
authors.initials: H
authors.lastname: Zimdahl
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.forename: Fiona
authors.initials: F
authors.lastname: Maciver
authors.forename: Michael
authors.initials: M
authors.lastname: Mueller
authors.forename: Oliver
authors.initials: O
authors.lastname: Hummel
authors.forename: Jan
authors.initials: J
authors.lastname: Monti
authors.forename: Vaclav
authors.initials: V
authors.lastname: Zidek
authors.forename: Alena
authors.initials: A
authors.lastname: Musilova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kren
authors.forename: Helen
authors.initials: H
authors.lastname: Causton
authors.forename: Laurence
authors.initials: L
authors.lastname: Game
authors.forename: Gabriele
authors.initials: G
authors.lastname: Born
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmidt
authors.forename: Anita
authors.initials: A
authors.lastname: Müller
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Cook
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: John
authors.initials: J
authors.lastname: Whittaker
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
mesh_terms: 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