Identification of novel SNPs in glioblastoma using targeted resequencing.
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 de...
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doaj-58b40ef6c7194c6c9b0b0f60523fdb292020-11-25T00:52:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e1815810.1371/journal.pone.0018158Identification of novel SNPs in glioblastoma using targeted resequencing.Andreas KellerChristian HarzMark MatzasBenjamin MederHugo A KatusNicole LudwigUlrike FischerEckart MeeseHigh-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.http://europepmc.org/articles/PMC3112142?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andreas Keller Christian Harz Mark Matzas Benjamin Meder Hugo A Katus Nicole Ludwig Ulrike Fischer Eckart Meese |
spellingShingle |
Andreas Keller Christian Harz Mark Matzas Benjamin Meder Hugo A Katus Nicole Ludwig Ulrike Fischer Eckart Meese Identification of novel SNPs in glioblastoma using targeted resequencing. PLoS ONE |
author_facet |
Andreas Keller Christian Harz Mark Matzas Benjamin Meder Hugo A Katus Nicole Ludwig Ulrike Fischer Eckart Meese |
author_sort |
Andreas Keller |
title |
Identification of novel SNPs in glioblastoma using targeted resequencing. |
title_short |
Identification of novel SNPs in glioblastoma using targeted resequencing. |
title_full |
Identification of novel SNPs in glioblastoma using targeted resequencing. |
title_fullStr |
Identification of novel SNPs in glioblastoma using targeted resequencing. |
title_full_unstemmed |
Identification of novel SNPs in glioblastoma using targeted resequencing. |
title_sort |
identification of novel snps in glioblastoma using targeted resequencing. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3112142?pdf=render |
work_keys_str_mv |
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