帕金森病与在整个富亮氨酸重复激酶2（LRRK2）中共同发现的低频等位基因。
Parkinson's disease and low frequency alleles found together throughout LRRK2.
作者信息
Paisán-Ruiz Coro, Washecka Nicole, Nath Priti, Singleton Andrew B, Corder Elizabeth H
机构信息
Molecular Neuroscience Department and Reta Lila Weston Laboratories, UCL Institute of Neurology, Queen Square, London, England.
出版信息
Ann Hum Genet. 2009 Jul;73(Pt 4):391-403. doi: 10.1111/j.1469-1809.2009.00524.x. Epub 2009 May 21.
Mutations within LRRK2, most notably p.G2019S, cause Parkinson's disease (PD) in rare monogenic families, and sporadic occurrences in diverse populations. We investigated variation throughout LRRK2 (84 SNPs; genotype or diplotype found for 49 LD blocks) for 275 cases (European ancestry, onset at age 60 or older) and 275 neurologically healthy control subjects (NINDS Neurogenetics Repository). Three grade-of-membership groups, i.e. genetic risk sets, were identified that exactly matched many subjects (cases: 46, 4, 137; controls: 0, 178, 0), and distinguished 94% of the subjects (i.e. >50% likeness to one set). Set I, affected, carried certain low frequency alleles located in multiple functional domains. Set II was unaffected. Set III, also affected, resembled set II except for slightly elevated frequencies of minor alleles not defining set I. We conclude that certain low frequency alleles distributed throughout LRRK2 are a genetic background to a third of cases, defining a distinct subset.
LRRK2基因内的突变，最显著的是p.G2019S突变，在罕见的单基因家族中会引发帕金森病（PD），在不同人群中也有散发病例。我们研究了275例患者（欧洲血统，60岁及以上发病）和275名神经功能正常的对照受试者（美国国立神经疾病和中风研究所神经遗传学库）LRRK2基因全长的变异情况（84个单核苷酸多态性；在49个连锁不平衡模块中发现的基因型或双倍型）。确定了三个成员等级组，即遗传风险组，与许多受试者完全匹配（病例：46、4、137；对照：0、178、0），并区分了94%的受试者（即与一组的相似度>50%）。第一组为患病组，携带位于多个功能域的某些低频等位基因。第二组未患病。第三组也为患病组，除了定义第一组的次要等位基因频率略有升高外，与第二组相似。我们得出结论，分布在LRRK2基因全长的某些低频等位基因是三分之一病例的遗传背景，定义了一个独特的亚组。
Zotero 插件