Rudolf Gabrielle, Bihoreau Marie Thérèse, Godfrey Richard F, Wilder Steven P, Cox Roger D, Lathrop Mark, Marescaux Christian, Gauguier Dominique
INSERM U398, Faculty of Medicine, Strasbourg, France.
Epilepsia. 2004 Apr;45(4):301-8. doi: 10.1111/j.0013-9580.2004.50303.x.
Generalized nonconvulsive absence seizures are characterized by the occurrence of synchronous and bilateral spike-and-wave discharges (SWDs) on electroencephalographic recordings, concomitant with behavioral arrest. The GAERS (genetic absence rats from Strasbourg) strain, a well-characterized inbred model for idiopathic generalized epilepsy, spontaneously develops EEG paroxysms that resemble those of typical absence seizures. The purpose of this study was to investigate the genetic control of SWD variables by using a combination of genetic analyses and electrophysiological measurements in an experimental cross derived from GAERS and Brown Norway (BN) rats.
SWD subphenotypes were quantified on EEG recordings performed at both 3 and 6 months in a cohort of 118 GAERS x BN F2 animals. A genome-wide scan of the F2 progenies was carried out with 146 microsatellite markers that were used to test each marker locus for evidence of genetic linkage to the SWD quantitative traits.
We identified three quantitative trait loci (QTLs) in chromosomes 4, 7, and 8 controlling specific SWD variables in the cross, including frequency, amplitude, and severity of SWDs. Age was a major factor influencing the detection of genetic linkage to the various components of the SWDs.
The identification of these QTLs demonstrates the polygenic control of SWDs in the GAERS strain. Genetic linkages to specific SWD features underline the complex mechanisms contributing to SWD development in idiopathic generalized epilepsy.
全身性非惊厥性失神发作的特征是脑电图记录上出现同步性双侧棘慢波放电（SWD），同时伴有行为停止。GAERS（来自斯特拉斯堡的遗传性失神大鼠）品系是一种特征明确的特发性全身性癫痫近交系模型，可自发出现类似于典型失神发作的脑电图阵发性活动。本研究的目的是通过对GAERS和棕色挪威（BN）大鼠杂交产生的实验性杂交后代进行遗传分析和电生理测量相结合的方法，研究SWD变量的遗传控制。
对118只GAERS×BN F2动物在3个月和6个月时进行的脑电图记录中的SWD亚表型进行量化。利用146个微卫星标记对F2后代进行全基因组扫描，以检测每个标记位点与SWD数量性状的遗传连锁证据。
我们在4号、7号和8号染色体上鉴定出三个数量性状基因座（QTL），它们控制杂交后代中特定的SWD变量，包括SWD的频率、幅度和严重程度。年龄是影响检测与SWD各组成部分遗传连锁的主要因素。
这些QTL的鉴定证明了GAERS品系中SWD的多基因控制。与特定SWD特征的遗传连锁强调了特发性全身性癫痫中导致SWD发生的复杂机制。
