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  • 1
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    Genetic analysis of radiation-induced changes in human gene expression (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-08
    Description: Humans are exposed to radiation through the environment and in medical settings. To deal with radiation-induced damage, cells mount complex responses that rely on changes in gene expression. These gene expression responses differ greatly between individuals and contribute to individual differences in response to radiation. Here we identify regulators that influence expression levels of radiation-responsive genes. We treated radiation-induced changes in gene expression as quantitative phenotypes, and conducted genetic linkage and association studies to map their regulators. For more than 1,200 of these phenotypes there was significant evidence of linkage to specific chromosomal regions. Nearly all of the regulators act in trans to influence the expression of their target genes; there are very few cis-acting regulators. Some of the trans-acting regulators are transcription factors, but others are genes that were not known to have a regulatory function in radiation response. These results have implications for our basic and clinical understanding of how human cells respond to radiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005325/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005325/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smirnov, Denis A -- Morley, Michael -- Shin, Eunice -- Spielman, Richard S -- Cheung, Vivian G -- R01 ES015733/ES/NIEHS NIH HHS/ -- R01 ES015733-01/ES/NIEHS NIH HHS/ -- R01 ES015733-04/ES/NIEHS NIH HHS/ -- R01 GM081930/GM/NIGMS NIH HHS/ -- R01 GM081930-08/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 May 28;459(7246):587-91. doi: 10.1038/nature07940. Epub 2009 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19349959" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; B-Lymphocytes/metabolism/radiation effects ; Caspases/metabolism ; Cell Line ; Chromosomes, Human/genetics ; *Gene Expression Profiling ; Gene Expression Regulation/*radiation effects ; Gene Knockdown Techniques ; Genetic Linkage ; Genetic Variation/*genetics ; Genome, Human/genetics ; Genotype ; Humans ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide/genetics ; *Toxicogenetics ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Widespread RNA and DNA sequence differences in the human transcriptome (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-05-21
    Description: The transmission of information from DNA to RNA is a critical process. We compared RNA sequences from human B cells of 27 individuals to the corresponding DNA sequences from the same individuals and uncovered more than 10,000 exonic sites where the RNA sequences do not match that of the DNA. All 12 possible categories of discordances were observed. These differences were nonrandom as many sites were found in multiple individuals and in different cell types, including primary skin cells and brain tissues. Using mass spectrometry, we detected peptides that are translated from the discordant RNA sequences and thus do not correspond exactly to the DNA sequences. These widespread RNA-DNA differences in the human transcriptome provide a yet unexplored aspect of genome variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204392/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204392/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Mingyao -- Wang, Isabel X -- Li, Yun -- Bruzel, Alan -- Richards, Allison L -- Toung, Jonathan M -- Cheung, Vivian G -- R01 HG005854/HG/NHGRI NIH HHS/ -- R01 HG005854-01/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jul 1;333(6038):53-8. doi: 10.1126/science.1207018. Epub 2011 May 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21596952" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Amino Acid Sequence ; B-Lymphocytes ; Base Sequence ; Cell Line ; Cerebral Cortex/cytology ; DNA/chemistry/*genetics ; Exons ; Expressed Sequence Tags ; Fibroblasts ; Gene Expression Profiling ; *Genetic Variation ; *Genome, Human ; Genotype ; Humans ; Mass Spectrometry ; Middle Aged ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Protein Biosynthesis ; Proteins/chemistry ; Proteome/chemistry ; RNA, Messenger/chemistry/*genetics ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Skin/cytology ; Untranslated Regions
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Genetics. Genetic control of hotspots (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheung, Vivian G -- Sherman, Stephanie L -- Feingold, Eleanor -- R01 HG001880/HG/NHGRI NIH HHS/ -- R01 HG001880-09S1/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):791-2. doi: 10.1126/science.1187155.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, USA. vcheung@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20150474" target="_blank"〉PubMed〈/a〉
    Keywords: Aneuploidy ; Animals ; Base Sequence ; Chromatin/*metabolism ; *Crossing Over, Genetic ; DNA/chemistry/*metabolism ; Genetic Association Studies ; Genetic Variation ; Heterozygote ; Histone-Lysine N-Methyltransferase/*genetics/metabolism ; Humans ; Meiosis/*genetics ; Mice ; *Recombination, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
    Electronic Resource
    Electronic Resource
    Integration of cytogenetic landmarks into the draft sequence of the human genome (2001)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 409 (2001), S. 953-958 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/409953a0
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    Paper (German National Licenses)
    Fulltext
  • 5
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    Whole genome amplification using a degenerate oligonucleotide primer allows hundreds of genotypes to be performed on less than one nanogram of genomic DNA (1996)
    National Academy of Sciences
    Details
    Publication Date: 1996-12-10
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Genome-Wide Association Study of Meiotic Recombination Phenotypes (2016)
    Genetics Society of America (GSA)
    Details
    Publication Date: 2016-12-08
    Description: Meiotic recombination is an essential step in gametogenesis, and is one that also generates genetic diversity. Genome-wide association studies (GWAS) and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination. Other genes have been identified by GWAS, but those results have not been replicated. In this study, using new datasets, we characterized additional recombination phenotypes to uncover novel candidates and further dissect the role of already known loci. We used three datasets totaling 1562 two-generation families, including 3108 parents with 4304 children. We estimated five different recombination phenotypes including two novel phenotypes (average recombination counts within recombination hotspots and outside of hotspots) using dense SNP array genotype data. We then performed gender-specific and combined-sex genome-wide association studies (GWAS) meta-analyses. We replicated associations for several previously reported recombination genes, including RNF212 and PRDM9 . By looking specifically at recombination events outside of hotspots, we showed for the first time that PRDM9 has different effects in males and females. We identified several new candidate loci, particularly for recombination events outside of hotspots. These include regions near the genes SPINK6 , EVC2 , ARHGAP25 , and DLGAP2 . This study expands our understanding of human meiotic recombination by characterizing additional features that vary across individuals, and identifying regulatory variants influencing the numbers and locations of recombination events.
    Electronic ISSN: 2160-1836
    Topics: Biology
    Published by Genetics Society of America (GSA)
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  • 7
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    Stress-induced changes in gene interactions in human cells (2014)
    Oxford University Press
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    Publication Date: 2014-02-11
    Description: Cells respond to variable environments by changing gene expression and gene interactions. To study how human cells response to stress, we analyzed the expression of 〉5000 genes in cultured B cells from nearly 100 normal individuals following endoplasmic reticulum stress and exposure to ionizing radiation. We identified thousands of genes that are induced or repressed. Then, we constructed coexpression networks and inferred interactions among genes. We used coexpression and machine learning analyses to study how genes interact with each other in response to stress. The results showed that for most genes, their interactions with each other are the same at baseline and in response to different stresses; however, a small set of genes acquired new interacting partners to engage in stress-specific responses. These genes with altered interacting partners are associated with diseases in which endoplasmic reticulum stress response or sensitivity to radiation has been implicated. Thus, our findings showed that to understand disease-specific pathways, it is important to identify not only genes that change expression levels but also those that alter interactions with other genes.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Identification of polymorphic antioxidant response elements in the human genome (2007)
    Oxford University Press
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    Publication Date: 2007-06-27
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 9
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    Integration of cytogenetic landmarks into the draft sequence of the human genome (2001)
    Springer Nature
    Details
    Publication Date: 2001-02-01
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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