Chromosomal mapping of genetic loci controlling absence epilepsy phenotypes in the WAG/Rij rat.
OBJECTIVE
The WAG/Rij rat is among the most appropriate models for the study of spontaneous childhood absence epilepsy, without complex neurologic disorders that are associated with some mouse models for absence epilepsy. Previous studies have allowed the identification of distinct types of spike-wave discharges (SWDs) characterizing seizures in this strain. The purpose of this study was to investigate the genetic basis of electroencephalographic (EEG) properties of SWDs.


METHODS
An intercross was derived from WAG/Rij and ACI inbred strains that are known to differ substantially in the number of SWDs. Phenotypic analyses based on 23-h EEG recording in all progenies allowed the quantification of type I and type II SWD phenotypes. A genome-wide scan was performed with 145 microsatellite markers, which were used to test for evidence of genetic linkage to SWD quantitative phenotypes.


RESULTS
We were able to map quantitative trait loci independently, controlling type I and type II SWD variables to rat chromosomes 5 and 9. Strongest linkages were obtained for D5Mgh15 and total duration of type II SWD (lod, 3.64) and for D9Rat103 and the average duration of type I SWD (lod, 3.91). These loci were denoted T2swd/wag and T1swd/wag, respectively.


CONCLUSIONS
The independent genetic control of type I and type II SWDs underlines the complexity of the molecular mechanisms participating in SWDs. The identification of these genetic loci represents an important step in our fundamental knowledge of the architecture of SWDs and may provide new insights for resolving the genetic heterogeneity of absence epilepsy.
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, England, United Kingdom.
Dominique
D
Gauguier
Gilles
G
van Luijtelaar
Marie Thérèse
MT
Bihoreau
Steven P
SP
Wilder
Richard F
RF
Godfrey
Jo
J
Vossen
Anton
A
Coenen
Roger D
RD
Cox
D000818:Animals; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000706:statistics & numerical data*; D004832:Epilepsy, Absence / Q000175:diagnosis / Q000235:genetics*; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar
D005819:Genetic Markers