title: Dynamic genetic architecture of metabolic syndrome attributes in the rat.
abstract: The polydactylous rat strain (PD/Cub) is a highly inbred (F > 90) genetic model of metabolic syndrome. The aim of this study was to analyze the genetic architecture of the metabolic derangements found in the PD/Cub strain and to assess its dynamics in time and in response to diet and medication. We derived a PD/Cub x BN/Cub (Brown Norway) F2 intercross population of 149 male rats and performed metabolic profiling and genotyping and multiple levels of genetic linkage and statistical analyses at five different stages of ontogenesis and after high-sucrose diet feeding and dexamethasone administration challenges. The interval mapping analysis of 83 metabolic and morphometric traits revealed over 50 regions genomewide with significant or suggestive linkage to one or more of the traits in the segregating PD/Cub x BN/Cub population. The multiple interval mapping showed that, in addition to "single" quantitative train loci, there are more than 30 pairs of loci across the whole genome significantly influencing the variation of particular traits in an epistatic fashion. This study represents the first whole genome analysis of metabolic syndrome in the PD/Cub model and reveals several new loci previously not connected to the genetics of insulin resistance and dyslipidemia. In addition, it attempts to present the concept of "dynamic genetic architecture" of metabolic syndrome attributes, evidenced by shifts in the genetic determination of syndrome features during ontogenesis and during adaptation to the dietary and pharmacological influences.
authors.affiliation: Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Montreal, Canada.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Seda
authors.forename: Frantisek
authors.initials: F
authors.lastname: Liska
authors.forename: Drahomira
authors.initials: D
authors.lastname: Krenova
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kazdova
authors.forename: Lucie
authors.initials: L
authors.lastname: Sedova
authors.forename: Tomas
authors.initials: T
authors.lastname: Zima
authors.forename: Junzheng
authors.initials: J
authors.lastname: Peng
authors.forename: Kveta
authors.initials: K
authors.lastname: Pelinkova
authors.forename: Johanne
authors.initials: J
authors.lastname: Tremblay
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kren
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D050171:Dyslipidemias / Q000235:genetics / Q000378:metabolism; D008040:Genetic Linkage; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains / Q000235:genetics* / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D013395:Sucrose; D003907:Dexamethasone