Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14.
Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance and the genes involved are yet to be fully established. A genome wide single nucleotide polymorphism (SNP)-based high density linkage scan was carried out using 41 nuclear pedigrees with at least two affected members. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, p<0.0001; HLOD=3.3, alpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1.
Chioza
Barry A
BA
Institute of Child Health, University College London, London, UK. b.chioza@ucl.ac.uk
Aicardi
Jean
J
Aschauer
Harald
H
Brouwer
Oebele
O
Callenbach
Petra
P
Covanis
Athanasios
A
Dooley
Joseph M
JM
Dulac
Olivier
O
Durner
Martina
M
Eeg-Olofsson
Orvar
O
Feucht
Martha
M
Friis
Mogens Laue
ML
Guerrini
Renzo
R
Kjeldsen
Marianne Juel
MJ
Nabbout
Rima
R
Nashef
Lina
L
Sander
Thomas
T
Sirén
Auli
A
Wirrell
Elaine
E
McKeigue
Paul
P
Robinson
Robert
R
Gardiner
R Mark
RM
Everett
Kate V
KV
D017668:Age of Onset; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004832:Epilepsy, Absence / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008297:Male; D018579:Patient Selection; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*