• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>International Journal of Molecular Epidemiology and Genetics >Next generation sequencing of CLU, PICALM and CR1: pitfalls and potential solutions
【24h】

Next generation sequencing of CLU, PICALM and CR1: pitfalls and potential solutions

机译：CLU，PICALM和CR1的下一代测序：陷阱和潜在解决方案

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

CLU, PICALM and CR1 were identified as genetic risk factors for late onset Alzheimer’s disease (AD) in two large genome wide association studies (GWAS) published in 2009, but the variants that convey this alteration in disease risk, and how the genes relate to AD pathology is yet to be discovered. A next generation sequencing (NGS) project was conducted targeting CLU, CR1 and PICALM, in 96 AD samples (8 pools of 12), in an attempt to discover rare variants within these AD associated genes. Inclusion of repetitive regions in the design of the SureSelect capture lead to significant issues in alignment of the data, leading to poor specificity and a lower than expected depth of coverage. A strong positive correlation (0.964, p<0.001) was seen between NGS and 1000 genome project frequency estimates. Of the ~170 “novel” variants detected in the genes, seven SNPs, all of which were present in multiple sample pools, were selected for validation by Sanger sequencing. Two SNPs were successfully validated by this method, and shown to be genuine variants, while five failed validation. These spurious SNP calls occurred as a result of the presence of small indels and mononucleotide repeats, indicating such features should be regarded with caution, and validation via an independent method is important for NGS variant calls.
机译：在2009年发表的两项大型全基因组关联研究（GWAS）中，CLU，PICALM和CR1被确定为迟发性阿尔茨海默氏病（AD）的遗传危险因素，但这些变体传达了疾病风险的这种改变以及这些基因与疾病的关系AD病理学尚未发现。进行了针对96个AD样本（8个库，共12个）的CLU，CR1和PICALM的下一代测序（NGS）项目，试图在这些AD相关基因中发现稀有变体。 SureSelect捕获的设计中包含重复区域会导致数据对齐方面出现重大问题，从而导致特异性差且覆盖深度低于预期范围。在NGS和1000个基因组计划频率估计值之间发现强正相关（0.964，p <0.001）。在基因中检测到的约170个“新”变体中，选择了七个SNP（均存在于多个样品池中）进行Sanger测序验证。通过这种方法成功验证了两个SNP，并显示是真正的变异，而五个验证失败。这些杂散的SNP调用是由于存在小插入缺失和单核苷酸重复而导致的，表​​明应谨慎考虑此类特征，并且通过独立方法进行的验证对于NGS变异调用非常重要。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号