Department of Neurology, Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
Transl Psychiatry. 2012 Nov 20;2(11):e192. doi: 10.1038/tp.2012.119.
Genetic variation, both single-nucleotide variations and copy number variations (CNV), contribute to changes in gene expression. In some cases these variations are meaningfully correlated with disease states. We hypothesized that in a genetically heterogeneous disorder such as sporadic Alzheimer's disease (AD), utilizing gene expression as a quantitative trait and CNVs as a genetic marker map within the same individuals in the context of case-control status may increase the power to detect relevant loci. Using this approach an 8-kb deletion was identified that contains a PAX6-binding site on chr2q33.3 upstream of CREB1 encoding the cAMP responsive element-binding protein1 transcription factor. The association of the CNV to AD was confirmed by a case-control association study consisting of the Texas Alzheimer Research and Care Consortium and NIA-LOAD Family Study data sets.
遗传变异，包括单核苷酸变异和拷贝数变异（CNV），都会导致基因表达的变化。在某些情况下，这些变异与疾病状态有明显的相关性。我们假设，在像散发性阿尔茨海默病（AD）这样遗传异质性的疾病中，利用基因表达作为数量性状，以及在病例对照状态下，在同一个体中作为遗传标记图谱的 CNVs，可以提高检测相关基因座的能力。通过这种方法，在 chr2q33.3 上鉴定到一个包含 PAX6 结合位点的 8kb 缺失，该区域位于编码 cAMP 反应元件结合蛋白 1 转录因子的 CREB1 上游。CNV 与 AD 的关联通过由德克萨斯州阿尔茨海默病研究与护理联盟和 NIA-LOAD 家族研究数据集组成的病例对照关联研究得到了证实。
