Genome-wide linkage scan for loci associated with epilepsy in Belgian shepherd dogs.
BACKGROUND
Idiopathic epilepsy in the Belgian shepherd dog is known to have a substantial genetic component. The objective of this study was to identify genomic regions associated with the expression of generalized seizures in the Belgian Tervuren and Sheepdog.


RESULTS
DNA from 366 dogs, of which 74 were classified as epileptic, representing two extended families were subjected to a genome-wide linkage scan using 410 microsatellite markers yielding informative coverage averaging 5.95 +/- 0.21 Mb. Though previous studies based on pedigree analyses proposed a major gene of influence, the present study demonstrated the trait to be highly polygenic. Studies of complex disorders in humans indicate that a liberal composite evaluation of genetic linkage is needed to identify underlying quantitative trait loci (QTLs). Four chromosomes yielded tentative linkage based upon LOD scores in excess of 1.0. Possible QTLs within these regions were supported also by analyses of multipoint linkage, allele frequency, TDT, and transmission of haplotype blocks.


CONCLUSIONS
Taken together the data tentatively indicate six QTLs, three on CFA 2, and one on each of CFA 6, 12, and 37, that support fine mapping for mutations associated with epilepsy in the Belgian shepherd. The study also underscores the complexity of genomic linkage studies for polygenic disorders.
Oberbauer
Anita M
AM
Department of Animal Science, University of California, Davis, CA, USA. amoberbauer@ucdavis.edu
Belanger
Janelle M
JM
Grossman
Deborah I
DI
Regan
Kelly R
KR
Famula
Thomas R
TR
D000818:Animals; D002874:Chromosome Mapping; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D004827:Epilepsy / Q000235:genetics* / Q000662:veterinary*; D005260:Female; D008040:Genetic Linkage; D008297:Male; D018895:Microsatellite Repeats; D040641:Quantitative Trait Loci