| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Centre de Recherche, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada; Institute of Biology and Medical Genetics, First Faculty of Medicine of Charles University and the General Teaching Hospital, Prague, Czech Republic; Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
2 Institute of Biology and Medical Genetics, First Faculty of Medicine of Charles University and the General Teaching Hospital, Prague, Czech Republic
3 Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
4 Institute of Clinical Biochemistry and Laboratory Diagnostics of the General Teaching Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic
5 Centre de Recherche, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: pavel.hamet{at}umontreal.ca.
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 PD/Cub x BN/Cub (Brown Norway) F2 intercross population of 149 male rats and performed metabolic profiling, genotyping, 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" QTLs, there are more than 30 pairs of loci across the whole genome significantly influencing the variation of particular traits in the 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 the syndrome features during ontogenesis and during adaptation to the dietary and pharmacological influences.
This article has been cited by other articles:
|
|
 |
|
  T. Mashimo, H. Ogawa, Z.-H. Cui, Y. Harada, K. Kawakami, J. Masuda, Y. Yamori, and T. Nabika Comprehensive QTL analysis of serum cholesterol levels before and after a high-cholesterol diet in SHRSP Physiol Genomics, July 18, 2007; 30(2): 95 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sedova, O. Seda, L. Kazdova, B. Chylikova, P. Hamet, J. Tremblay, V. Kren, and D. Krenova Sucrose feeding during pregnancy and lactation elicits distinct metabolic response in offspring of an inbred genetic model of metabolic syndrome Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1318 - E1324. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
