Identification of novel SNPs in glioblastoma using targeted resequencing.
Identification of novel SNPs in glioblastoma using targeted resequencing.
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DOI：
10.1371/journal.pone.0018158
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Meese E
中科院分区：
文献类型：
--
作者：
Keller A;Harz C;Matzas M;Meder B;Katus HA;Ludwig N;Fischer U;Meese E
高通量测序为发现可能表明某些疾病风险增加的遗传变异开辟了途径。将这些基因组数据与其他“组学”方法联系起来，有可能加深我们在分子水平上对致病过程的理解。为了检测多形性胶质母细胞瘤（GBM）的新单核苷酸多态性（SNP），我们使用了特异性靶点选择和下一代测序（NGS）的组合。我们制作了一个覆盖132个GBM相关基因外显子区域的微阵列，以富集两种GBM组织和相应患者白细胞中的靶序列。用Illumina对富集的靶基因进行测序，并将所得读数映射到人类基因组。通过这种方法，我们确定了超过6000个SNP，包括位于靶基因中的超过1300个SNP。整合全基因组关联研究（GWAS）目录和已知的疾病相关SNPs，我们发现几个检测到的SNPs先前与吸烟行为，体重指数，乳腺癌和高级别胶质瘤相关。特别地，基因SART 1中的rs660118 SNP的乳腺癌相关等位基因在胶质母细胞瘤患者中显示出接近两倍的频率，如通过桑格测序在独立对照组中验证的。此外，我们在21种GBM相关抗原中的20种中鉴定了SNP，进一步证明遗传变异与抗原的免疫原性显著相关。
High-throughput sequencing opens avenues to find genetic variations that may be indicative of an increased risk for certain diseases. Linking these genomic data to other “omics” approaches bears the potential to deepen our understanding of pathogenic processes at the molecular level. To detect novel single nucleotide polymorphisms (SNPs) for glioblastoma multiforme (GBM), we used a combination of specific target selection and next generation sequencing (NGS). We generated a microarray covering the exonic regions of 132 GBM associated genes to enrich target sequences in two GBM tissues and corresponding leukocytes of the patients. Enriched target genes were sequenced with Illumina and the resulting reads were mapped to the human genome. With this approach we identified over 6000 SNPs, including over 1300 SNPs located in the targeted genes. Integrating the genome-wide association study (GWAS) catalog and known disease associated SNPs, we found that several of the detected SNPs were previously associated with smoking behavior, body mass index, breast cancer and high-grade glioma. Particularly, the breast cancer associated allele of rs660118 SNP in the gene SART1 showed a near doubled frequency in glioblastoma patients, as verified in an independent control cohort by Sanger sequencing. In addition, we identified SNPs in 20 of 21 GBM associated antigens providing further evidence that genetic variations are significantly associated with the immunogenicity of antigens.
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