Liu X, Cheng R, Ye X, Verbitsky M, Kisselev S, Mejia-Santana H, Louis Ed, Cote Lj, Andrews H, Waters C, Ford B, Fahn S, Marder K, Lee Jh, Clark Ln
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Mol Genet Genomic Med. 2013 Sep;1(3):142-154. doi: 10.1002/mgg3.18.
To date, only one genome-wide study has assessed the contribution of CNVs to Parkinson's Disease (PD). We conducted a genome-wide scan for CNVs in a case-control dataset of Ashkenazi Jewish (AJ) origin (268 PD cases and 178 controls). Using high-confidence CNVs, we examined the global genome wide burden of large (≥100Kb) and rare (≤1% in the dataset) CNVs between cases and controls. A total of 986 such CNVs were observed in our dataset of 432 subjects. Overall global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications or number of genes affected by CNVs. Overall deletions (total CNV size and >2x frequency) were found 1.4 times more often in cases than in controls (p=0.019). The large CNVs (>500kb) were also significantly associated with PD (p=0.046, 1.24-folder higher in cases than in controls). Global burden was elevated for rare CNV regions. Specifically, for on Chr12p11.21, CNVs were observed only in PD cases (n=7) but not in controls (=0.028) and this was experimentally validated. A total of 81 PD cases carried a rare genic CNV that was absent in controls. Ingenuity pathway analysis (IPA) identified , , , and in the same disease pathway with known PD genes.
迄今为止，仅有一项全基因组研究评估了拷贝数变异（CNV）对帕金森病（PD）的影响。我们在一个源自阿什肯纳兹犹太人（AJ）的病例对照数据集中（268例PD患者和178名对照）进行了全基因组CNV扫描。利用高可信度的CNV，我们检查了病例组和对照组之间大的（≥100Kb）和罕见的（在数据集中≤1%）CNV的全基因组负担。在我们432名受试者的数据集中共观察到986个此类CNV。总体全基因组负担分析未发现病例组和对照组在CNV发生率、缺失或重复分布或受CNV影响的基因数量上有显著差异。总体缺失（总CNV大小和>2倍频率）在病例组中的发现频率是对照组的1.4倍（p = 0.019）。大的CNV（>500kb）也与PD显著相关（p = 0.046，病例组比对照组高1.24倍）。罕见CNV区域的全基因组负担有所升高。具体而言，在12号染色体p11.21区域，仅在PD病例中观察到CNV（n = 7），而对照组中未观察到（p = 0.028），且这一点得到了实验验证。共有81例PD病例携带了对照组中不存在的罕见基因CNV。 Ingenuity通路分析（IPA）在与已知PD基因相同的疾病通路中鉴定出了 、 、 和 。
