Association Screen of High Priority Positional Candidate Genes for Migraine

典型的偏头痛，是一种常见的，使人衰弱和痛苦的疾病，通常影响人们在他们最富有成效的几年（25%的女性和7.5%的男性）。世界卫生组织最近将偏头痛列为世界上20大主要残疾原因之一，其影响远远超出了痛苦的个人，对家庭和社区的影响。虽然偏头痛在我们的社会中非常普遍，但其病因仍然相对模糊，并且没有基于实验室的诊断测试来识别患有这种疾病的人。双胞胎研究表明，偏头痛具有显著的遗传成分，遗传率估计为33- 65%。因此，为了确定这种疾病的分子机制，我们一直在寻找与偏头痛共同遗传的基因组区域。由此产生的涉及756个澳大利亚家庭的全基因组连锁扫描发现了染色体5 q21上存在新的偏头痛基因的重要证据，以及染色体10 q22上存在基因的高度暗示性证据。重要的是，我们最近在一个独立的澳大利亚偏头痛家族集合中复制了5 q21和10 q22区域的连锁。因此，这些区域在我们的样本中识别偏头痛易感基因方面有很大的希望。使用生物信息学计算机辅助搜索公共数据库，我们已经在5 q21和10 q22区域内的基因的潜在候选人进行了排名。该项目将在768例病例和768例对照中筛选前21个候选基因，这些基因分别被高度选择用于家族性偏头痛的存在和不存在。我们提出的关联筛选高优先级基因在两个强烈牵连的地区有很高的权力，以确定常见的偏头痛易感性的基因。这些基因将为进一步阐明偏头痛的复杂分子途径提供线索，并最终有助于诊断测试和合理治疗策略的发展。

Typical migraine, is a frequent, debilitating and painful disorder that normally affects people during their most productive years (25% of females and 7.5% of males). The World Health Organization recently identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond the suffering individual, to the family and community. Although migraine is highly prevalent in our society, its aetiology remains relatively obscure and there are no laboratory based diagnostic tests that identify those who suffer from the disorder. Twin studies indicate that migraine has a significant genetic component, with heritability estimates of 33-65%. Therefore, in an effort to identify the molecular mechanisms underlying the disorder, we have been looking for genomic regions co-inherited (linked) with migraine. The resulting genome-wide linkage scan involving 756 Australian families found significant evidence for the presence of a novel migraine gene on chromosome 5q21 and highly suggestive evidence for a gene on chromosome 10q22. Importantly, we recently replicated linkage to the 5q21 and 10q22 regions in an independent collection of Australian migraine families. Consequently, these regions hold great promise for identifying migraine susceptibility genes in our sample. Using a bioinformatics computer-assisted search of public databases we have ranked the potential candidature of the genes within the 5q21 and 10q22 regions This project will screen the top 21 candidate genes in 768 cases and 768 controls highly selected for the presence and absence of familial migraine, respectively. Our proposed association screen of high priority genes in two strongly implicated regions has high power to identify genes underlying common migraine susceptibility. Such genes will provide clues to the further elucidation of the complex molecular pathways of migraine and , finally, will help in the development of diagnostic tests and rational treatment strategies.