Alizadeh Mehdi, Génin Emmanuelle, Babron Marie-Claude, Birebent Brigitte, Cournu-Rebeix Isabelle, Yaouanq Jacqueline, Dréano Stéphane, Sawcer Stephen, Compston Alastair, Clanet Michel, Edan Gilles, Fontaine Bertrand, Clerget-Darpoux Françoise, Semana Gilbert
Laboratoire d'Immunologie, UPRES EA 1257 (IFR97), Faculté de Médecine, 2 Avenue du Pr Léon Bernard CS 34317, 35043 Rennes Cedex, France.
J Neuroimmunol. 2003 Oct;143(1-2):74-8. doi: 10.1016/j.jneuroim.2003.08.015.
We report the results of a genome-wide screen for linkage disequilibrium (LD) in multiple sclerosis (MS) performed on 200 cases, 200 controls and 200 case-parent trios from France employing pooled DNA methodology. A total of 3510 microsatellite markers supplied through the GAMES collaborative were analysed and ranked according to their evidence for association. The most promising 117 markers were then followed up in a two-step validation process. In the first step, additional PCR of the DNA pools was performed in order to refine the ranking order. In the second step, markers were genotyped in individual cases and parents from the trio families. Seven markers showing nominally significant allele frequency differences between affected and unaffected emerged-D6S265, D12S1064, TNFa, D7S1824, D14S1426, D14S605 and D21S2051. These potential associations will require confirmation in further studies.
我们报告了一项针对多发性硬化症（MS）的全基因组连锁不平衡（LD）筛查结果。该筛查采用混合DNA方法，对来自法国的200例患者、200例对照以及200个病例-父母三联体进行了检测。分析了通过GAMES合作项目提供的总共3510个微卫星标记，并根据它们的关联证据进行排名。然后，对最有前景的117个标记进行了两步验证。第一步，对DNA池进行额外的聚合酶链反应（PCR），以完善排名顺序。第二步，对三联体家庭中的个体病例及其父母进行标记基因分型。结果出现了7个在患病和未患病个体之间显示出名义上显著等位基因频率差异的标记——D6S265、D12S1064、肿瘤坏死因子α（TNFa）、D7S1824、D14S1426、D14S605和D21S2051。这些潜在关联需要在进一步研究中得到证实。
