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  • 1
    Publication Date: 2015-06-10
    Description: Tumor-specific molecules are needed across diverse areas of oncology for use in early detection, diagnosis, prognosis and therapy. Large and growing public databases of transcriptome sequencing data (RNA-seq) derived from tumors and normal tissues hold the potential of yielding tumor-specific molecules, but because the data are new they have not...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2013-01-16
    Description: The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase acting on RNA (ADAR) enzymes...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2007-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murphy, K -- Frazer, K A -- Loots, G -- Rubin, E M -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2319a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17769838" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2001-11-27
    Description: Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patil, N -- Berno, A J -- Hinds, D A -- Barrett, W A -- Doshi, J M -- Hacker, C R -- Kautzer, C R -- Lee, D H -- Marjoribanks, C -- McDonough, D P -- Nguyen, B T -- Norris, M C -- Sheehan, J B -- Shen, N -- Stern, D -- Stokowski, R P -- Thomas, D J -- Trulson, M O -- Vyas, K R -- Frazer, K A -- Fodor, S P -- Cox, D R -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1719-23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Perlegen Sciences, Inc., 2021 Stierlin Court, Mountain View, CA 94043, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721056" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Alleles ; Animals ; Chromosomes, Human, Pair 21/*genetics ; Continental Population Groups/genetics ; Ethnic Groups/genetics ; Gene Frequency/genetics ; Genetic Variation/genetics ; Genome, Human ; Haplotypes/*genetics ; Humans ; Hybrid Cells/metabolism ; Mutation/genetics ; Oligonucleotide Array Sequence Analysis/*methods ; Polymorphism, Single Nucleotide/*genetics ; Random Allocation ; Sensitivity and Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2001-02-07
    Description: Long-range regulatory elements are difficult to discover experimentally; however, they tend to be conserved among mammals, suggesting that cross-species sequence comparisons should identify them. To search for regulatory sequences, we examined about 1 megabase of orthologous human and mouse sequences for conserved noncoding elements with greater than or equal to 70% identity over at least 100 base pairs. Ninety noncoding sequences meeting these criteria were discovered, and the analysis of 15 of these elements found that about 70% were conserved across mammals. Characterization of the largest element in yeast artificial chromosome transgenic mice revealed it to be a coordinate regulator of three genes, interleukin-4, interleukin-13, and interleukin-5, spread over 120 kilobases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loots, G G -- Locksley, R M -- Blankespoor, C M -- Wang, Z E -- Miller, W -- Rubin, E M -- Frazer, K A -- AI30663/AI/NIAID NIH HHS/ -- GM-5748202/GM/NIGMS NIH HHS/ -- HL56385/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):136-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10753117" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomes, Human, Pair 5/genetics ; Conserved Sequence ; *DNA-Binding Proteins ; Fungal Proteins/biosynthesis/genetics ; Gene Expression Regulation ; Humans ; Interleukin-13/biosynthesis/*genetics ; Interleukin-4/biosynthesis/*genetics ; Interleukin-5/biosynthesis/*genetics ; Kinesin/biosynthesis/genetics ; Mice ; Mice, Transgenic ; Physical Chromosome Mapping ; *Regulatory Sequences, Nucleic Acid ; *Saccharomyces cerevisiae Proteins ; Species Specificity ; Th1 Cells/immunology ; Th2 Cells/immunology ; Transgenes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2005-02-19
    Description: Individual differences in DNA sequence are the genetic basis of human variability. We have characterized whole-genome patterns of common human DNA variation by genotyping 1,586,383 single-nucleotide polymorphisms (SNPs) in 71 Americans of European, African, and Asian ancestry. Our results indicate that these SNPs capture most common genetic variation as a result of linkage disequilibrium, the correlation among common SNP alleles. We observe a strong correlation between extended regions of linkage disequilibrium and functional genomic elements. Our data provide a tool for exploring many questions that remain regarding the causal role of common human DNA variation in complex human traits and for investigating the nature of genetic variation within and between human populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinds, David A -- Stuve, Laura L -- Nilsen, Geoffrey B -- Halperin, Eran -- Eskin, Eleazar -- Ballinger, Dennis G -- Frazer, Kelly A -- Cox, David R -- New York, N.Y. -- Science. 2005 Feb 18;307(5712):1072-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Perlegen Sciences Inc., 2021 Stierlin Court, Mountain View, CA 94043, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15718463" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/*genetics ; Algorithms ; Asian Continental Ancestry Group/*genetics ; Case-Control Studies ; Chromosome Mapping ; Databases, Genetic ; European Continental Ancestry Group/*genetics ; Female ; Gene Frequency ; Genetic Markers ; Genetic Predisposition to Disease ; *Genetic Variation ; *Genome, Human ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Male ; Multifactorial Inheritance ; *Polymorphism, Single Nucleotide ; Recombination, Genetic ; Risk Factors ; Selection, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2011-02-11
    Description: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the 9p21 gene desert associated with coronary artery disease (CAD) and type 2 diabetes. Despite evidence for a role of the associated interval in neighbouring gene regulation, the biological underpinnings of these genetic associations with CAD or type 2 diabetes have not yet been explained. Here we identify 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and six times denser than the whole genome (P 〈 6.55 x 10(-33)). The CAD risk alleles of SNPs rs10811656 and rs10757278 are located in one of these enhancers and disrupt a binding site for STAT1. Lymphoblastoid cell lines homozygous for the CAD risk haplotype show no binding of STAT1, and in lymphoblastoid cell lines homozygous for the CAD non-risk haplotype, binding of STAT1 inhibits CDKN2BAS (also known as CDKN2B-AS1) expression, which is reversed by short interfering RNA knockdown of STAT1. Using a new, open-ended approach to detect long-distance interactions, we find that in human vascular endothelial cells the enhancer interval containing the CAD locus physically interacts with the CDKN2A/B locus, the MTAP gene and an interval downstream of IFNA21. In human vascular endothelial cells, interferon-gamma activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus, including STAT1-binding, long-range enhancer interactions and altered expression of neighbouring genes. Our findings establish a link between CAD genetic susceptibility and the response to inflammatory signalling in a vascular cell type and thus demonstrate the utility of genome-wide association study findings in directing studies to novel genomic loci and biological processes important for disease aetiology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079517/" 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/PMC3079517/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harismendy, Olivier -- Notani, Dimple -- Song, Xiaoyuan -- Rahim, Nazli G -- Tanasa, Bogdan -- Heintzman, Nathaniel -- Ren, Bing -- Fu, Xiang-Dong -- Topol, Eric J -- Rosenfeld, Michael G -- Frazer, Kelly A -- 1R21CA152613-01/CA/NCI NIH HHS/ -- 1U54RR025204/RR/NCRR NIH HHS/ -- 1UL1RR025774/RR/NCRR NIH HHS/ -- 1UL1RR031980-01/RR/NCRR NIH HHS/ -- CA97134/CA/NCI NIH HHS/ -- DK018477/DK/NIDDK NIH HHS/ -- DK074868/DK/NIDDK NIH HHS/ -- DK39949/DK/NIDDK NIH HHS/ -- DK74686/DK/NIDDK NIH HHS/ -- HL065445/HL/NHLBI NIH HHS/ -- L65445/PHS HHS/ -- NS34934/NS/NINDS NIH HHS/ -- P01 AG025204/AG/NIA NIH HHS/ -- P01 AG025204-01/AG/NIA NIH HHS/ -- R01 CA097134/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK018477-35/DK/NIDDK NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 DK039949-29/DK/NIDDK NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 HL065445-12/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R21 CA152613/CA/NCI NIH HHS/ -- R21 CA152613-01/CA/NCI NIH HHS/ -- R21 CA152613-02/CA/NCI NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- U01 HL107442/HL/NHLBI NIH HHS/ -- UL1 RR025774/RR/NCRR NIH HHS/ -- UL1 RR025774-01/RR/NCRR NIH HHS/ -- UL1 RR031980/RR/NCRR NIH HHS/ -- UL1 RR031980-01/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Feb 10;470(7333):264-8. doi: 10.1038/nature09753.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics and Rady's Children's Hospital, University of California at San Diego, School of Medicine, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307941" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Line ; Chromatin/drug effects/genetics/metabolism ; Chromosomes, Human, Pair 9/*genetics ; Conserved Sequence/genetics ; Coronary Artery Disease/*genetics ; Cyclin-Dependent Kinase Inhibitor p15/genetics ; Diabetes Mellitus, Type 2/genetics ; Endothelial Cells/drug effects/metabolism ; Enhancer Elements, Genetic/*genetics ; European Continental Ancestry Group/genetics ; Gene Expression Regulation/drug effects/genetics ; Gene Knockdown Techniques ; Genetic Predisposition to Disease/*genetics ; *Genetic Variation ; Genome-Wide Association Study ; Haplotypes/genetics ; HeLa Cells ; Humans ; Interferon-alpha/genetics ; Interferon-gamma/*pharmacology ; Linkage Disequilibrium ; Male ; Polymorphism, Single Nucleotide/genetics ; Protein Binding/drug effects ; Purine-Nucleoside Phosphorylase/genetics ; STAT1 Transcription Factor/biosynthesis/deficiency/genetics/metabolism ; Signal Transduction/*drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2007-07-21
    Description: The genomes of individuals from the same species vary in sequence as a result of different evolutionary processes. To examine the patterns of, and the forces shaping, sequence variation in Arabidopsis thaliana, we performed high-density array resequencing of 20 diverse strains (accessions). More than 1 million nonredundant single-nucleotide polymorphisms (SNPs) were identified at moderate false discovery rates (FDRs), and approximately 4% of the genome was identified as being highly dissimilar or deleted relative to the reference genome sequence. Patterns of polymorphism are highly nonrandom among gene families, with genes mediating interaction with the biotic environment having exceptional polymorphism levels. At the chromosomal scale, regional variation in polymorphism was readily apparent. A scan for recent selective sweeps revealed several candidate regions, including a notable example in which almost all variation was removed in a 500-kilobase window. Analyzing the polymorphisms we describe in larger sets of accessions will enable a detailed understanding of forces shaping population-wide sequence variation in A. thaliana.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clark, Richard M -- Schweikert, Gabriele -- Toomajian, Christopher -- Ossowski, Stephan -- Zeller, Georg -- Shinn, Paul -- Warthmann, Norman -- Hu, Tina T -- Fu, Glenn -- Hinds, David A -- Chen, Huaming -- Frazer, Kelly A -- Huson, Daniel H -- Scholkopf, Bernhard -- Nordborg, Magnus -- Ratsch, Gunnar -- Ecker, Joseph R -- Weigel, Detlef -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):338-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641193" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Arabidopsis/*genetics ; Base Sequence ; Chromosomes, Plant/genetics ; Computational Biology ; Gene Frequency ; Genes, Plant ; *Genetic Variation ; *Genome, Plant ; Molecular Sequence Data ; *Polymorphism, Genetic ; *Polymorphism, Single Nucleotide ; Selection, Genetic ; Sequence Analysis, DNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-05-17
    Description: Cellular membranes act as signaling platforms and control solute transport. Membrane receptors, transporters, and enzymes communicate with intracellular processes through protein-protein interactions. Using a split-ubiquitin yeast two-hybrid screen that covers a test-space of 6.4 x 10(6) pairs, we identified 12,102 membrane/signaling protein interactions from Arabidopsis. Besides confirmation of expected interactions such as heterotrimeric G protein subunit interactions and aquaporin oligomerization, 〉99% of the interactions were previously unknown. Interactions were confirmed at a rate of 32% in orthogonal in planta split-green flourescent protein interaction assays, which was statistically indistinguishable from the confirmation rate for known interactions collected from literature (38%). Regulatory associations in membrane protein trafficking, turnover, and phosphorylation include regulation of potassium channel activity through abscisic acid signaling, transporter activity by a WNK kinase, and a brassinolide receptor kinase by trafficking-related proteins. These examples underscore the utility of the membrane/signaling protein interaction network for gene discovery and hypothesis generation in plants and other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Alexander M -- Xuan, Yuanhu -- Xu, Meng -- Wang, Rui-Sheng -- Ho, Cheng-Hsun -- Lalonde, Sylvie -- You, Chang Hun -- Sardi, Maria I -- Parsa, Saman A -- Smith-Valle, Erika -- Su, Tianying -- Frazer, Keith A -- Pilot, Guillaume -- Pratelli, Rejane -- Grossmann, Guido -- Acharya, Biswa R -- Hu, Heng-Cheng -- Engineer, Cawas -- Villiers, Florent -- Ju, Chuanli -- Takeda, Kouji -- Su, Zhao -- Dong, Qunfeng -- Assmann, Sarah M -- Chen, Jin -- Kwak, June M -- Schroeder, Julian I -- Albert, Reka -- Rhee, Seung Y -- Frommer, Wolf B -- New York, N.Y. -- Science. 2014 May 16;344(6185):711-6. doi: 10.1126/science.1251358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. ; Department of Physics, Pennsylvania State University, University Park, PA 16802, USA. ; Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. Department of Plant Pathology, Physiology, and Weed Science, Virginia Polytechnic University and State University, Blacksburg, VA 24061, USA. ; Department of Biology, Pennsylvania State University, University Park, PA 16802, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. ; Cell and Developmental Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA. ; Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. Michigan State University-U.S. Department of Energy (MSU-DOE) Plant Research Laboratory and Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. Center for Plant Aging Research, Institute for Basic Science, Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea. ; Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. wfrommer@stanford.edu srhee@carnegiescience.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833385" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cell Membrane/*metabolism ; Membrane Proteins/genetics/*metabolism ; *Protein Interaction Maps ; Signal Transduction ; Two-Hybrid System Techniques
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2000-02-01
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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