28
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Copy number variation is highly correlated with differential gene expression: a pan-cancer study

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Cancer is a heterogeneous disease with many genetic variations. Lines of evidence have shown copy number variations (CNVs) of certain genes are involved in development and progression of many cancers through the alterations of their gene expression levels on individual or several cancer types. However, it is not quite clear whether the correlation will be a general phenomenon across multiple cancer types.

          Methods

          In this study we applied a bioinformatics approach integrating CNV and differential gene expression mathematically across 1025 cell lines and 9159 patient samples to detect their potential relationship.

          Results

          Our results showed there is a close correlation between CNV and differential gene expression and the copy number displayed a positive linear influence on gene expression for the majority of genes, indicating that genetic variation generated a direct effect on gene transcriptional level. Another independent dataset is utilized to revalidate the relationship between copy number and expression level. Further analysis show genes with general positive linear influence on gene expression are clustered in certain disease-related pathways, which suggests the involvement of CNV in pathophysiology of diseases.

          Conclusions

          This study shows the close correlation between CNV and differential gene expression revealing the qualitative relationship between genetic variation and its downstream effect, especially for oncogenes and tumor suppressor genes. It is of a critical importance to elucidate the relationship between copy number variation and gene expression for prevention, diagnosis and treatment of cancer.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          Global variation in copy number in the human genome.

          Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Fine-scale structural variation of the human genome.

            Inversions, deletions and insertions are important mediators of disease and disease susceptibility. We systematically compared the human genome reference sequence with a second genome (represented by fosmid paired-end sequences) to detect intermediate-sized structural variants >8 kb in length. We identified 297 sites of structural variation: 139 insertions, 102 deletions and 56 inversion breakpoints. Using combined literature, sequence and experimental analyses, we validated 112 of the structural variants, including several that are of biomedical relevance. These data provide a fine-scale structural variation map of the human genome and the requisite sequence precision for subsequent genetic studies of human disease.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Human housekeeping genes are compact.

                Bookmark

                Author and article information

                Contributors
                xin_shao@zju.edu.cn
                lvn1987@zju.edu.cn
                liaojie@zju.edu.cn
                314010178@zju.edu.cn
                21719061@zju.edu.cn
                ai_ni@zju.edu.cn
                xudonghang@zju.edu.cn
                fanxh@zju.edu.cn
                Journal
                BMC Med Genet
                BMC Med. Genet
                BMC Medical Genetics
                BioMed Central (London )
                1471-2350
                9 November 2019
                9 November 2019
                2019
                : 20
                : 175
                Affiliations
                [1 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, College of Pharmaceutical Sciences, , Zhejiang University, ; Hangzhou, 310058 China
                [2 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Department of Pharmacy, The 2nd Affiliated Hospital, School of Medicine, , Zhejiang University, ; Hangzhou, 310009 China
                Author information
                http://orcid.org/0000-0002-6336-3007
                Article
                909
                10.1186/s12881-019-0909-5
                6842483
                31706287
                74ab651b-80ec-4e70-bf76-f7cee89ab20e
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 December 2018
                : 15 October 2019
                Funding
                Funded by: National Youth Top-notch Talent Support Program
                Award ID: W02070098
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81774153
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Genetics
                copy number variation,differential gene expression,concordance,pan-cancer
                Genetics
                copy number variation, differential gene expression, concordance, pan-cancer

                Comments

                Comment on this article