University Diabetes Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Genetics, Strategic Center for Diabetes Research, King Saud University, Riyadh, PO, Box 245, Saudi Arabia.
Gene. 2018 Jul 15;663:157-164. doi: 10.1016/j.gene.2018.04.019. Epub 2018 Apr 22.
In the case of diabetes and other complex diseases, the challenge has always been to find genetic markers that explain the excess risk associated with development of the disease. In the last 12 years, advances in genotyping technology provided substantial development in the discovery of loci contributing to Type 2 diabetes (T2D) susceptibility. Therefore, the aim of this study is to custom design, for the first time in Arab world, an "Arab Diabetes Gene Centric Array" (ADGCA) that assays 643, 745 SNP markers including 50,617 diabetes associated SNPs. The array content was designed after comprehensive literature search prioritizing Diabetes associated SNPs. PCA was performed to evaluate the relationship between world populations and the Saudi population in building the backbone for the array. A genotype data matrix for PCA analysis was produced by including the genotypes of the 270 HapMap samples including JPT, CHB, YRI and CEU to genotypes of the 1457 Saudi samples. Imputation was executed using IMPUTE2 software and the 1000GP Phase III reference panel. All markers incorporated to ADGCA were validated. Quality checks and evaluation of its capacity and performance as a platform for genetic screening for T2D was performed using the latest stastical tools available. We were successful in designing ADGCA as a custom made chip array designed with a motive to capture genetic variation in loci known or reported to be associated with the development of T2D. However, implementation of ADGCA is currently being performed by our research group using 2000 DNA samples respectively from diabetic and non diabetic individuals which could further validate the use of ADGSA in genetic screening of T2D.
在糖尿病和其他复杂疾病的情况下，挑战一直是找到解释与疾病发展相关的额外风险的遗传标记。在过去的 12 年中，基因分型技术的进步为发现导致 2 型糖尿病（T2D）易感性的基因座提供了实质性的发展。因此，本研究的目的是首次在阿拉伯世界定制设计一个“阿拉伯糖尿病基因中心阵列”（ADGCA），该阵列检测 643,745 个 SNP 标记，包括 50,617 个与糖尿病相关的 SNP。该阵列的内容是在全面文献检索后设计的，优先考虑与糖尿病相关的 SNP。进行 PCA 以评估世界人群与沙特人群之间的关系，为该阵列构建主干。通过包括 270 个 HapMap 样本的基因型（包括 JPT、CHB、YRI 和 CEU）和 1457 个沙特样本的基因型，生成用于 PCA 分析的基因型数据矩阵。使用 IMPUTE2 软件和 1000GP Phase III 参考面板执行 IMPUTE。将所有纳入 ADGCA 的标记进行验证。使用最新的统计工具进行质量检查和评估其作为 T2D 遗传筛查平台的能力和性能。我们成功地设计了 ADGCA，作为一种定制的芯片阵列，旨在捕获已知或报道与 T2D 发展相关的基因座的遗传变异。然而，ADGCA 的实施目前正在由我们的研究小组使用分别来自糖尿病和非糖尿病个体的 2000 个 DNA 样本进行，这可以进一步验证 ADGSA 在 T2D 遗传筛查中的应用。
