gene dosage

Summary

Summary: The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.

Top Publications

  1. pmc The landscape of somatic copy-number alteration across human cancers
    Rameen Beroukhim
    Cancer Program and Medical and Population Genetics Group, The Broad Institute of M I T and Harvard, 7 Cambridge Center
    Nature 463:899-905. 2010
  2. pmc Functional impact of global rare copy number variation in autism spectrum disorders
    Dalila Pinto
    The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
    Nature 466:368-72. 2010
  3. pmc PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data
    Kai Wang
    Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Genome Res 17:1665-74. 2007
  4. pmc Mechanisms of change in gene copy number
    P J Hastings
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
    Nat Rev Genet 10:551-64. 2009
  5. pmc Population analysis of large copy number variants and hotspots of human genetic disease
    Andy Itsara
    Department of Genome Sciences, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Am J Hum Genet 84:148-61. 2009
  6. pmc Diversity of human copy number variation and multicopy genes
    Peter H Sudmant
    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
    Science 330:641-6. 2010
  7. ncbi Stochastic gene expression in a single cell
    Michael B Elowitz
    Laboratory of Cancer Biology, Center for Studies in Physics and Biology, Rockefeller University, New York, NY 10021, USA
    Science 297:1183-6. 2002
  8. ncbi Copy number variation: new insights in genome diversity
    Jennifer L Freeman
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Genome Res 16:949-61. 2006
  9. pmc CNV-seq, a new method to detect copy number variation using high-throughput sequencing
    Chao Xie
    Department of Biological Sciences, National University of Singapore, Singapore
    BMC Bioinformatics 10:80. 2009
  10. pmc Analysis of copy number variations among diverse cattle breeds
    George E Liu
    USDA ARS, ANRI, Bovine Functional Genomics Laboratory, Beltsville, Maryland 20705, USA
    Genome Res 20:693-703. 2010

Detail Information

Publications270 found, 100 shown here

  1. pmc The landscape of somatic copy-number alteration across human cancers
    Rameen Beroukhim
    Cancer Program and Medical and Population Genetics Group, The Broad Institute of M I T and Harvard, 7 Cambridge Center
    Nature 463:899-905. 2010
    ..Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types...
  2. pmc Functional impact of global rare copy number variation in autism spectrum disorders
    Dalila Pinto
    The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
    Nature 466:368-72. 2010
    ..Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways...
  3. pmc PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data
    Kai Wang
    Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Genome Res 17:1665-74. 2007
    ..3%. Our results demonstrate the feasibility of whole-genome fine-mapping of CNVs via high-density SNP genotyping...
  4. pmc Mechanisms of change in gene copy number
    P J Hastings
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
    Nat Rev Genet 10:551-64. 2009
    ..For example, cellular stress might induce repair of broken replication forks to switch from high-fidelity homologous recombination to non-homologous repair, thus promoting copy number change...
  5. pmc Population analysis of large copy number variants and hotspots of human genetic disease
    Andy Itsara
    Department of Genome Sciences, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Am J Hum Genet 84:148-61. 2009
    ..g., 3q29, 16p12, and 15q25.2) for further investigation. This study provides one of the first analyses of large, rare (0.1%-1%) CNVs in the general population, with insights relevant to future analyses of genetic disease...
  6. pmc Diversity of human copy number variation and multicopy genes
    Peter H Sudmant
    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
    Science 330:641-6. 2010
    ..Our approach makes ~1000 genes accessible to genetic studies of disease association...
  7. ncbi Stochastic gene expression in a single cell
    Michael B Elowitz
    Laboratory of Cancer Biology, Center for Studies in Physics and Biology, Rockefeller University, New York, NY 10021, USA
    Science 297:1183-6. 2002
    ..These results establish a quantitative foundation for modeling noise in genetic networks and reveal how low intracellular copy numbers of molecules can fundamentally limit the precision of gene regulation...
  8. ncbi Copy number variation: new insights in genome diversity
    Jennifer L Freeman
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Genome Res 16:949-61. 2006
    ..Current efforts are directed toward a more comprehensive cataloging and characterization of CNVs that will provide the basis for determining how genomic diversity impacts biological function, evolution, and common human diseases...
  9. pmc CNV-seq, a new method to detect copy number variation using high-throughput sequencing
    Chao Xie
    Department of Biological Sciences, National University of Singapore, Singapore
    BMC Bioinformatics 10:80. 2009
    ..Array comparative genomic hybridization (aCGH) is commonly used for CNV detection, but the microarray platform has a number of inherent limitations...
  10. pmc Analysis of copy number variations among diverse cattle breeds
    George E Liu
    USDA ARS, ANRI, Bovine Functional Genomics Laboratory, Beltsville, Maryland 20705, USA
    Genome Res 20:693-703. 2010
    ..Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research...
  11. pmc Relative impact of nucleotide and copy number variation on gene expression phenotypes
    Barbara E Stranger
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
    Science 315:848-53. 2007
    ..Interrogation of the genome for both types of variants may be an effective way to elucidate the causes of complex phenotypes and disease in humans...
  12. pmc Global variation in copy number in the human genome
    Richard Redon
    The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Nature 444:444-54. 2006
    ..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...
  13. pmc Inferring tumor progression from genomic heterogeneity
    Nicholas Navin
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genome Res 20:68-80. 2010
    ..By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth...
  14. pmc Copy number variation at 1q21.1 associated with neuroblastoma
    Sharon J Diskin
    Division of Oncology and Center for Childhood Cancer Research, Children s Hospital of Philadelphia, USA
    Nature 459:987-91. 2009
    ..These data demonstrate that inherited copy number variation at 1q21.1 is associated with neuroblastoma and implicate a previously unknown neuroblastoma breakpoint family gene in early tumorigenesis of this childhood cancer...
  15. ncbi Circular binary segmentation for the analysis of array-based DNA copy number data
    Adam B Olshen
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Biostatistics 5:557-72. 2004
    ..The method is evaluated by simulation and is demonstrated on cell line data with known copy number alterations and on a breast cancer cell line data set...
  16. ncbi A census of amplified and overexpressed human cancer genes
    Thomas Santarius
    The Wellcome Trust Sanger Centre, Wellcome Trust Genome Campus Hinxton, Cambridge, UK
    Nat Rev Cancer 10:59-64. 2010
    ..In a census of the published literature we have identified 77 genes for which there is good evidence of involvement in the development of human cancer...
  17. pmc Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing
    Peter J Campbell
    Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nat Genet 40:722-9. 2008
    ..The results demonstrate the feasibility of systematic, genome-wide characterization of rearrangements in complex human cancer genomes, raising the prospect of a new harvest of genes associated with cancer using this strategy...
  18. pmc Maize inbreds exhibit high levels of copy number variation (CNV) and presence/absence variation (PAV) in genome content
    Nathan M Springer
    Department of Plant Biology, University of Minnesota, Saint Paul, Minnesota, USA
    PLoS Genet 5:e1000734. 2009
    ..Haplotype-specific PAVs contain hundreds of single-copy, expressed genes that may contribute to heterosis and to the extraordinary phenotypic diversity of this important crop...
  19. ncbi Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster
    J J Emerson
    Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA
    Science 320:1629-31. 2008
    ..Among duplications, those overlapping exons or introns, as well as those falling on the X chromosome, seem to be subject to stronger purifying selection...
  20. pmc The genomic architecture of segmental duplications and associated copy number variants in dogs
    Thomas J Nicholas
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    Genome Res 19:491-9. 2009
    ..Our results provide insight into mechanisms of canine genome evolution and generate a valuable resource for future evolutionary and phenotypic studies...
  21. ncbi Detection of large-scale variation in the human genome
    A John Iafrate
    Department of Pathology, Brigham and Women s Hospital, 20 Shattuck St, Thorn 6 28, Boston, Massachusetts 02115, USA
    Nat Genet 36:949-51. 2004
    ..This previously unappreciated heterogeneity may underlie certain human phenotypic variation and susceptibility to disease and argues for a more dynamic human genome structure...
  22. pmc Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing
    Hansoo Park
    Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea
    Nat Genet 42:400-5. 2010
    ..These common CNVs in Asian populations will be a useful resource for subsequent genetic studies in these populations, and the new method of calling absolute CNVs will be essential for applying CNV data to personalized medicine...
  23. ncbi A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders
    Jennifer A Lee
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston TX, 77030, USA
    Cell 131:1235-47. 2007
    ..We propose that complex duplication and deletion rearrangements associated with PMD, and potentially other nonrecurrent rearrangements, may be explained by this replication-based mechanism...
  24. pmc Strong association of de novo copy number mutations with autism
    Jonathan Sebat
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Science 316:445-9. 2007
    ..Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized...
  25. pmc Identification of shared single copy nuclear genes in Arabidopsis, Populus, Vitis and Oryza and their phylogenetic utility across various taxonomic levels
    Jill M Duarte
    Department of Biology and the Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
    BMC Evol Biol 10:61. 2010
    ....
  26. pmc De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot
    Steven C Greenway
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    Nat Genet 41:931-5. 2009
    ..Our findings predict that at least 10% (4.5-15.5%, 95% confidence interval) of sporadic nonsyndromic TOF cases result from de novo CNVs and suggest that mutations within these loci might be etiologic in other cases of TOF...
  27. pmc Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs
    Joshua M Korn
    Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:1253-60. 2008
    ..The Birdsuite software is applied here to data from the Affymetrix SNP 6.0 array. Additionally, we describe a method, implemented in PLINK, to utilize these combined SNP and CNV genotypes for association testing with a phenotype...
  28. pmc Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
    Sebastien Jacquemont
    Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
    Nature 478:97-102. 2011
    ..The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance...
  29. pmc Paucity of genes on the Drosophila X chromosome showing male-biased expression
    Michael Parisi
    Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892 8028, USA
    Science 299:697-700. 2003
    ..These data indicate that the X chromosome is a disfavored location for genes selectively expressed in males...
  30. pmc Accurate, high-throughput typing of copy number variation using paralogue ratios from dispersed repeats
    John A L Armour
    Institute of Genetics, University of Nottingham, Nottingham, NG7 2UH, UK
    Nucleic Acids Res 35:e19. 2007
    ....
  31. pmc Structural variation of chromosomes in autism spectrum disorder
    Christian R Marshall
    The Centre for Applied Genomics, The Hospital for Sick Children, Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L7, Canada
    Am J Hum Genet 82:477-88. 2008
    ..Structural variants were found in sufficiently high frequency influencing ASD to suggest that cytogenetic and microarray analyses be considered in routine clinical workup...
  32. ncbi Integrated detection and population-genetic analysis of SNPs and copy number variation
    Steven A McCarroll
    Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    Nat Genet 40:1166-74. 2008
    ..Most common, diallelic CNPs were in strong linkage disequilibrium with SNPs, and most low-frequency CNVs segregated on specific SNP haplotypes...
  33. pmc A penalized matrix decomposition, with applications to sparse principal components and canonical correlation analysis
    Daniela M Witten
    Department of Statistics, Stanford University, Stanford, CA 94305, USA
    Biostatistics 10:515-34. 2009
    ..We apply this penalized CCA method to simulated data and to a genomic data set consisting of gene expression and DNA copy number measurements on the same set of samples...
  34. ncbi Genomic and transcriptional aberrations linked to breast cancer pathophysiologies
    Koei Chin
    Comprehensive Cancer Center, 2340 Sutter Street, University of California, San Francisco, San Francisco, California 94143
    Cancer Cell 10:529-41. 2006
    ..Nine of these (FGFR1, IKBKB, ERBB2, PROCC, ADAM9, FNTA, ACACA, PNMT, and NR1D1) are considered druggable. Low-level CNAs appear to contribute to cancer progression by altering RNA and cellular metabolism...
  35. pmc High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications
    Tamim H Shaikh
    Division of Genetics, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Genome Res 19:1682-90. 2009
    ..Together, this analysis and annotation provides a useful resource to assist with the assessment of CNVs in the contexts of human variation, disease susceptibility, and clinical molecular diagnostics...
  36. ncbi Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300
    T P Yao
    Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 93:361-72. 1998
    ..Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and cbp...
  37. pmc Copy number variation and evolution in humans and chimpanzees
    George H Perry
    School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona 85287, USA
    Genome Res 18:1698-710. 2008
    ..In particular, duplications and deletions of genes with inflammatory response and cell proliferation functions may have been fixed by positive selection and involved in the adaptive phenotypic differentiation of humans and chimpanzees...
  38. pmc A robust statistical method for case-control association testing with copy number variation
    Chris Barnes
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
    Nat Genet 40:1245-52. 2008
    ..We illustrate the power of these methods for testing for association with binary and quantitative traits, and have made this software available as the R package CNVtools...
  39. ncbi alpha-Synuclein locus triplication causes Parkinson's disease
    A B Singleton
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 302:841. 2003
  40. ncbi Turning a hobby into a job: how duplicated genes find new functions
    Gavin C Conant
    Division of Animal Sciences, University of Missouri Columbia, 163B Animal Sciences Center, 920 East Campus Drive, Columbia, Missouri 65211 5300, USA
    Nat Rev Genet 9:938-50. 2008
    ..mutations that directly impart new functions, subdivision of ancestral functions and selection for changes in gene dosage. Interestingly, in many cases the 'new' function of one copy is a secondary property that was always present, ..
  41. pmc A snapshot of CNVs in the pig genome
    João Fadista
    Group of Molecular Genetics and Systems Biology, Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, Aarhus University, Tjele, Denmark
    PLoS ONE 3:e3916. 2008
    ..This CNV snapshot analysis is the first of its kind in the porcine genome and constitutes the basis for a better understanding of porcine phenotypes and genotypes with the prospect of identifying important economic traits...
  42. ncbi Genomic rearrangements and sporadic disease
    James R Lupski
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 604B and Texas Children s Hospital Houston, Texas 77030, USA
    Nat Genet 39:S43-7. 2007
    ..Widespread implementation of high-resolution genome analyses to detect de novo copy-number variation may identify the cause of traits previously intractable to conventional genetic analyses...
  43. ncbi Key role for gene dosage and synaptic homeostasis in autism spectrum disorders
    Roberto Toro
    Human Genetics and Cognitive Functions, Institut Pasteur, 75015 Paris, France
    Trends Genet 26:363-72. 2010
    ..Second, the majority of the mutations apparently affect a single allele, suggesting a key role for gene dosage in susceptibility to ASD...
  44. pmc Identification of miniature inverted-repeat transposable elements (MITEs) and biogenesis of their siRNAs in the Solanaceae: new functional implications for MITEs
    Hanhui Kuang
    Plant Gene Expression Center, Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California 94720, USA
    Genome Res 19:42-56. 2009
    ..We provide evidence that DICER-LIKE4 (DCL4) may also play a role in MITE siRNA generation in the Solanaceae...
  45. pmc Relating CNVs to transcriptome data at fine resolution: assessment of the effect of variant size, type, and overlap with functional regions
    Andreas Schlattl
    European Molecular Biology Laboratory EMBL, Genome Biology Research Unit, 69117 Heidelberg, Germany
    Genome Res 21:2004-13. 2011
    ..Our results suggest that association studies can gain in resolution and power by including fine-scale CNV information, such as those obtained from population-scale sequencing...
  46. pmc FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity
    Manuela Fanciulli
    Physiological Genomics and Medicine Group, UK Medical Research Council MRC Clinical Sciences Centre, Imperial College, London W12 0NN, UK
    Nat Genet 39:721-3. 2007
    ..Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity...
  47. ncbi Recombination regulation by transcription-induced cohesin dissociation in rDNA repeats
    Takehiko Kobayashi
    National Institute for Basic Biology, SOKENDAI, School of Life Science, 38 Nishigonaka, Myodaijicho, Okazaki, 444 8585 Japan
    Science 309:1581-4. 2005
    ..This transcription is regulated by the silencing gene, SIR2, and by copy number. Transcription-induced cohesin dissociation may be a general mechanism of recombination regulation...
  48. ncbi Association of higher DEFB4 genomic copy number with Crohn's disease
    Robert W Bentley
    Department of Pathology, University of Otago, Christchurch, New Zealand
    Am J Gastroenterol 105:354-9. 2010
    ..Here, we analyze association of DEFB4 copy number with CD in a New Zealand case-control cohort of European origin...
  49. ncbi Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma
    Levi A Garraway
    Department of Medical Oncology, and Melanoma Program in Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nature 436:117-22. 2005
    ..Together, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific cancer development and tumour progression...
  50. pmc Mapping DNA structural variation in dogs
    Wei Kang Chen
    Center for Molecular and Human Genetics, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio 43205, USA
    Genome Res 19:500-9. 2009
    ..We discuss how a catalog of structural variation in dogs will accelerate the identification of the genetic basis of canine traits and diseases, beginning with the use of whole genome association and candidate-CNV/gene approaches...
  51. ncbi An active DNA transposon family in rice
    Ning Jiang
    Department of Plant Biology, University of Georgia, Athens, Georgia 30602, USA
    Nature 421:163-7. 2003
    ..Since the domestication of rice mPing MITEs have been amplified preferentially in cultivars adapted to environmental extremes-a situation that is reminiscent of the genomic shock theory for transposon activation...
  52. ncbi Accurate and objective copy number profiling using real-time quantitative PCR
    Barbara D'haene
    Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
    Methods 50:262-70. 2010
    ..The provided guidelines will most certainly improve the quality and reliability of your qPCR-based copy number screening...
  53. ncbi Functional coherence of the human Y chromosome
    B T Lahn
    Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 278:675-80. 1997
    ..The coherence of the NRY's gene content contrasts with the apparently haphazard content of most eukaryotic chromosomes...
  54. pmc High resolution discovery and confirmation of copy number variants in 90 Yoruba Nigerians
    Hajime Matsuzaki
    Affymetrix, Inc, 3420 Central Expressway, Santa Clara, CA 95051, USA
    Genome Biol 10:R125. 2009
    ..More recently, whole genome sequencing of individuals has revealed an abundance of shorter CNVs with lengths < 1 kb...
  55. pmc Advances in autism genetics: on the threshold of a new neurobiology
    Brett S Abrahams
    Neurology Department, and Semel Institute for Neuroscience and Behaviour, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095 1769 USA
    Nat Rev Genet 9:341-55. 2008
    ..Systems biology approaches, including array-based expression profiling, are poised to provide additional insights into this group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a dominant theme...
  56. pmc Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia
    Pharath Lim
    Institut Pasteur in Cambodia, Phnom Penh, Cambodia
    Malar J 8:11. 2009
    ....
  57. pmc Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
    Joseph T Glessner
    Center for Applied Genomics, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Nature 459:569-73. 2009
    ....
  58. pmc Identifying autism loci and genes by tracing recent shared ancestry
    Eric M Morrow
    Division of Genetics, Children s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA
    Science 321:218-23. 2008
    ....
  59. pmc Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients
    Federico Cappuzzo
    Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico, Department of Oncology Hematology, University of Milan School of Medicine, IRCCS Istituto Clinico Humanitas, Rozzano, Italy
    J Clin Oncol 27:1667-74. 2009
    ..To investigate the prognostic role of genomic gain for MET and epidermal growth factor receptor (EGFR) genes in surgically resected non-small-cell lung cancer (NSCLC)...
  60. ncbi KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer
    Astrid Lievre
    Universite Paris Descartes, Institut National de la Sante et de la Recherche Medicale UMR 775, Paris, France
    Cancer Res 66:3992-5. 2006
    ..The EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment...
  61. ncbi High-throughput assessment of transgene copy number in sugarcane using real-time quantitative PCR
    Rosanne E Casu
    CSIRO Plant Industry, Queensland Bioscience Precinct, St Lucia, QLD, Australia
    Plant Cell Rep 31:167-77. 2012
    ..This method requires much less input DNA, can be performed much earlier in the production of transgenic sugarcane plants and allows much more efficient assessment of numerous potentially transgenic lines than Southern blotting...
  62. ncbi Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target
    Jeeyun Lee
    Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
    Oncol Rep 25:1517-24. 2011
    ..However, the predictive role of MET amplification for treatment response should be further explored in upcoming clinical trials...
  63. pmc GPHMM: an integrated hidden Markov model for identification of copy number alteration and loss of heterozygosity in complex tumor samples using whole genome SNP arrays
    Ao Li
    Department of Electronic Science and Technology, University of Science and Technology of China
    Nucleic Acids Res 39:4928-41. 2011
    ....
  64. pmc Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior
    Brenda Murdoch
    School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
    PLoS Genet 9:e1003241. 2013
    ....
  65. pmc Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios
    Johan Staaf
    Department of Oncology, Clinical Sciences, Lund University, SE 22185 Lund, Sweden
    BMC Bioinformatics 9:409. 2008
    ..Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples...
  66. ncbi Gene copy number variation and common human disease
    M Fanciulli
    Imperial College London, Hammersmith Hospital, London, W12 0NN, UK
    Clin Genet 77:201-13. 2010
    ....
  67. ncbi Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree
    K P Lesch
    ADHD Clinical Research Network, Unit for Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
    Mol Psychiatry 16:491-503. 2011
    ..These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome...
  68. pmc Integrated genome-wide DNA copy number and expression analysis identifies distinct mechanisms of primary chemoresistance in ovarian carcinomas
    Dariush Etemadmoghadam
    Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Clin Cancer Res 15:1417-27. 2009
    ..We analyzed somatic DNA copy number variation and gene expression data to identify key mechanisms associated with primary resistance in advanced-stage serous cancers...
  69. pmc Analysis of DNA copy number alterations in ovarian serous tumors identifies new molecular genetic changes in low-grade and high-grade carcinomas
    Kuan Ting Kuo
    Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
    Cancer Res 69:4036-42. 2009
    ..Our study provides a genome-wide homozygous deletion profile in HG serous carcinomas, which can serve as a molecular foundation to study tumor suppressors in ovarian cancer...
  70. pmc Copy number, linkage disequilibrium and disease association in the FCGR locus
    Heather A Niederer
    Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Hills Road, Cambridge CB2 0XY, UK
    Hum Mol Genet 19:3282-94. 2010
    ..Further interpretations of contributions to pathogenesis by FcgammaRs must be made in the context of LD involving CNV regions...
  71. pmc Allele-specific copy number analysis of tumors
    Peter Van Loo
    Department of Genetics, Institute for Cancer Research, Clinic for Cancer and Surgery, Oslo University Hospital, Montebello, N 0310 Oslo, Norway
    Proc Natl Acad Sci U S A 107:16910-5. 2010
    ..We hypothesize that these alternative alleles have a different influence on breast carcinoma development...
  72. pmc Copy number variation in intron 1 of SOX5 causes the Pea-comb phenotype in chickens
    Dominic Wright
    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
    PLoS Genet 5:e1000512. 2009
    ..The study provides novel insight into the nature of mutations that contribute to phenotypic evolution and is the first description of a spontaneous and fully viable mutation in this developmentally important gene...
  73. pmc Copy-number variation: the balance between gene dosage and expression in Drosophila melanogaster
    Jun Zhou
    Department of Organismic and Evolutionary Biology, Harvard University, USA
    Genome Biol Evol 3:1014-24. 2011
    ..expression data collected from some of the same substitution lines to investigate relationships between CNV gene dosage and expression...
  74. ncbi Copy number variations and cancer susceptibility
    Adam Shlien
    Department of Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada
    Curr Opin Oncol 22:55-63. 2010
    ..This review discusses current understanding of the characteristics of CNVs in the human genome and explores the emerging discoveries of both constitutional and somatic CNVs in an ever-expanding variety of human cancers...
  75. pmc Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients
    Florence Magrangeas
    INSERM U892, Universite de Nantes, Nantes, France
    Blood 118:675-8. 2011
    ..3% of samples. Moreover, this catastrophic event confers a poor outcome. Because chromothripsis appears to occur in a single crisis, our results suggest that high-risk MM patients use this novel way of cancer evolution...
  76. ncbi Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer
    Toshimi Takano
    Division of Internal Medicine, National Cancer Center Hospital, 5 1 1 Tsukiji, Chuo Ku, Tokyo 104 0045, Japan
    J Clin Oncol 23:6829-37. 2005
    ..To evaluate epidermal growth factor receptor (EGFR) mutations and copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib...
  77. ncbi Absolute and relative QPCR quantification of plasmid copy number in Escherichia coli
    Changsoo Lee
    School of Environmental Science and Engineering, Pohang University of Science and Technology, San 31, Hyoja Dong, Nam Gu, Pohang, Kyungbuk 790 784, Republic of Korea
    J Biotechnol 123:273-80. 2006
    ..The primer sets designed in this study can be used to determine plasmid copy number of any recombinant E. coli with a plasmid vector having bla gene...
  78. pmc Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European America
    Yan Yang
    Center for Molecular and Human Genetics, Columbus Children s Research Institute, Columbus, OH 43205, USA
    Am J Hum Genet 80:1037-54. 2007
    ..This work demonstrates how gene CNV and its related polymorphisms are associated with the susceptibility to a human complex disease...
  79. ncbi Copy number variation in human health, disease, and evolution
    Feng Zhang
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Annu Rev Genomics Hum Genet 10:451-81. 2009
    ..By various molecular mechanisms, including gene dosage, gene disruption, gene fusion, position effects, etc...
  80. ncbi A faster circular binary segmentation algorithm for the analysis of array CGH data
    E S Venkatraman
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Bioinformatics 23:657-63. 2007
    ..This makes the full permutation approach computationally prohibitive for the newer arrays that contain tens of thousands markers and highlights the need for a faster algorithm...
  81. ncbi Copy-number variations associated with neuropsychiatric conditions
    Edwin H Cook
    Institute for Juvenile Research, Department of Psychiatry, University of Illinois, 1747 West Roosevelt Road, Chicago, Illinois 60608, USA
    Nature 455:919-23. 2008
    ..The complexity of neuropsychiatric genetics, however, dictates that assessment of the biomedical relevance of copy-number variants and the genes that they affect needs to be considered in an integrated context...
  82. ncbi Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer
    Francesco Graziano
    Azienda Ospedaliera Ospedali Riuniti Marche Nord 61122, Pesaro, Italy
    J Clin Oncol 29:4789-95. 2011
    ..To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF...
  83. pmc Targeted expression of MYCN causes neuroblastoma in transgenic mice
    W A Weiss
    G W Hooper Foundation, and Department of Neurology, University of California, San Francisco 94143 0552, USA
    EMBO J 16:2985-95. 1997
    ....
  84. pmc An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors
    D Chitale
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Oncogene 28:2773-83. 2009
    ....
  85. pmc Comparative genomics of wild type yeast strains unveils important genome diversity
    Laura Carreto
    Departamento de Biologia and CESAM, Universidade de Aveiro, 3810 193 Aveiro, Portugal
    BMC Genomics 9:524. 2008
    ..This suggests that genome plasticity provides important genetic diversity upon which natural selection mechanisms can operate...
  86. ncbi Complex human chromosomal and genomic rearrangements
    Feng Zhang
    Department of Molecular and Human Genetics, Baylor College of Medicine, and Texas Children s Hospital, Houston, TX 77030, USA
    Trends Genet 25:298-307. 2009
    ....
  87. pmc Large recurrent microdeletions associated with schizophrenia
    Hreinn Stefansson
    CNS Division, deCODE Genetics, Sturlugata 8, IS 101 Reykjavik, Iceland
    Nature 455:232-6. 2008
    ..CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia...
  88. pmc Acquired copy number alterations in adult acute myeloid leukemia genomes
    Matthew J Walter
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 106:12950-5. 2009
    ....
  89. ncbi Regional copy number-independent deregulation of transcription in cancer
    Nicolas Stransky
    UMR 144 Centre National de la Recherche Scientifique CNRS Institut Curie, 75248 Paris Cedex 05, France
    Nat Genet 38:1386-96. 2006
    ..We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation...
  90. pmc The role of mitochondrial DNA copy number in mammalian fertility
    Timothy Wai
    Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal, Quebec, Canada
    Biol Reprod 83:52-62. 2010
    ....
  91. ncbi Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer
    Anna Bergamaschi
    Department of Genetics, Institute for Cancer Research, Rikshospitalet Radiumhospitalet Medical Center, Oslo, Norway
    Genes Chromosomes Cancer 45:1033-40. 2006
    ..This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat..
  92. ncbi Large-scale copy number polymorphism in the human genome
    Jonathan Sebat
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Science 305:525-8. 2004
    ..We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease...
  93. pmc The pitfalls of platform comparison: DNA copy number array technologies assessed
    Christina Curtis
    Department of Oncology, University of Cambridge, Addenbrooke s Hopsital, Hills Road, Cambridge CB20XZ, UK
    BMC Genomics 10:588. 2009
    ..By careful consideration and avoidance of potential sources of bias, we aim to provide a fair assessment of platform performance...
  94. ncbi Natural history and evolutionary principles of gene duplication in fungi
    Ilan Wapinski
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 449:54-61. 2007
    ..Surprisingly, paralogous modules of genes rarely arise, even after whole-genome duplication. Rather, gene duplication may drive the modularization of functional networks through specialization, thereby disentangling cellular systems...
  95. pmc Sensitive and accurate detection of copy number variants using read depth of coverage
    Seungtai Yoon
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genome Res 19:1586-92. 2009
    ..Our results suggest that analysis of read depth is an effective approach for the detection of CNVs, and it captures structural variants that are refractory to established PEM-based methods...
  96. ncbi CGHcall: calling aberrations for array CGH tumor profiles
    Mark A van de Wiel
    Department of Pathology, VU University Medical Center, PO Box 7057, 1007MB Amsterdam, The Netherlands
    Bioinformatics 23:892-4. 2007
    ..By incorporating more than three classes, CGHcall improves detection of single copy gains and amplifications. Moreover, it allows effective inclusion of chromosome arm information...
  97. pmc Integrative analysis reveals the direct and indirect interactions between DNA copy number aberrations and gene expression changes
    Hyunju Lee
    Harvard Partners Center for Genetics and Genomics, Informatics Program, Children s Hospital, Department of Cardiology, Children s Hospital, Boston, MA, USA
    Bioinformatics 24:889-96. 2008
    ..Most studies so far have focused on how a CNA affects the expression levels of those genes contained within that CNA...
  98. pmc A single-array preprocessing method for estimating full-resolution raw copy numbers from all Affymetrix genotyping arrays including GenomeWideSNP 5 & 6
    Henrik Bengtsson
    Department of Statistics, University of California, Berkeley, California, USA
    Bioinformatics 25:2149-56. 2009
    ..It is applicable to all Affymetrix genotyping arrays, including the recent ones that also contain non-polymorphic probes. A reference signal is only needed at the last step when calculating relative CNs...
  99. ncbi Gene dosage of the common variant 9p21 predicts severity of coronary artery disease
    Sonny Dandona
    John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada
    J Am Coll Cardiol 56:479-86. 2010
    The purpose of this study was to test the hypothesis that 9p21 gene dosage determines the severity of coronary artery disease (CAD).

Research Grants71

  1. Targeting p53-Dependent Repigmentation in Vitiligo
    TAMARA G TERZIAN; Fiscal Year: 2013
    ..Guillermina Lozano. Her studies on gene dosage effects of p53 in development and tumorigenesis and uncovering the mechanism of action of mutant p53 have ..
  2. Role of troponin T isoforms in nemaline myopathy
    Jian Ping Jin; Fiscal Year: 2012
    ..We will examine the potential effect of decreased slow TnT gene dosage on muscle function and the cytotoxicity of truncated slow TnT for links to muscle degeneration in ANM...
  3. Sphingosine 1-phosphate receptors in vascular homeostasis and pathology
    TIMOTHY TUN HLA; Fiscal Year: 2012
    ..The ability of S1P2R to modulate S1P1R-dependent effects will be tested by varying the gene dosage of S1p2r in the context of the S1P1R hypermorph...
  4. OLFACTORY RECEPTOR COPY NUMBER ASSOCIATION WITH AGE AT ONSET OF ALZHEIMER DISEASE
    Kinga Szigeti; Fiscal Year: 2013
    ..2 (reference sequence position 19.3-19.5 Mb) where gene dosage is associated with AAO of AD (genome-wide adjusted p<0...
  5. NFAT Signaling and Down Syndrome
    Gerald R Crabtree; Fiscal Year: 2012
    ..The observation that a 1.5-fold increase in gene dosage can produce significant developmental effects suggest that the genes at fault might function synergistically...
  6. 2011 Epigenetics Gordon Research Conference
    Marisa S Bartolomei; Fiscal Year: 2011
    ..of such intriguing phenomena as X chromosome inactivation, gametic imprinting, position effect variegation, gene dosage control, paramutation, nucleolar dominance, transposon silencing and RNA-mediated DNA methylation will be ..
  7. Molecular Basis of Nuchal Edema
    Young Kwon Hong; Fiscal Year: 2013
    ..Based on these data, we now build a novel model for the molecular basis of NE: Increased gene dosage of DSCR1 and Dyrk1a results in down-regulation of COUP- TFII and subsequent activation of Notch signal in LECs ..
  8. Regulation of 22q11 Genes in Embroyonic and Adult Forebrain
    Anthony S LaMantia; Fiscal Year: 2013
    ..1.) We will assess interaction between diminished 22q11 gene dosage and inductive signaling that influences cortical regional identity and neurogenic capacity...
  9. Environmental and genetic regulation of copy number variation (CNV)
    THOMAS PETES; Fiscal Year: 2010
    ..We will use a cassette that contains two yeast genes SFA1 and CUP1 that confer gene dosage-dependent tolerance to formaldehyde and copper, respectively...
  10. Regulation of Hepatic Uptake of Endogenous Signaling Molecules and Xenobiotics
    Ivan Csanaky; Fiscal Year: 2013
    ....
  11. Genetic Regulation of Metabolic and Fibrotic Programs in Hypertrophic Heart
    M A Q Siddiqui; Fiscal Year: 2013
    ..Our experimental model for examining this hypothesis are mice with reduced CLP-1 gene dosage, CLP-1+/- heterozygous mice, rendered hypertrophic physically or by crossing with established mouse models of ..
  12. Mechanisms of Increased Lung Fibrosis in Males
    ISELA CARIDAD VALERA; Fiscal Year: 2013
    ..These data suggest a possible role of X chromosome gene dosage in modulating susceptibility to and damage from inflammatory diseases...
  13. GENETIC CONTROL OF PROTEOGLYCAN METABOLISM
    Jeffrey D Esko; Fiscal Year: 2010
    ..we will search for regulatory genes in the system using multi-copy plasmidsto inactivatethe pathway through gene dosage effects. 2. Analyze the function of GIcA transferase-I in mice...
  14. Role of JAK2V617F in the Pathogenesis of Myeloproliferative Disorders.
    Golam Mohi; Fiscal Year: 2013
    ..We will examine the effects of JAK2V617F gene dosage (heterozygosity versus homozygosity) on MPD phenotype...
  15. Neurobiology of Aggression Co-morbidity in Mouse Model of Idic15 Autism
    Matthew P Anderson; Fiscal Year: 2013
    ..our newly created conditional Ube3a ON transgenic mice for temporally-induced over- expression of the idic15 gene dosage of Ube3a to determine the developmental time period when excess Ube3a generates the exaggerated aggression ..
  16. Genetic Variations and Development of Vesicoureteral Reflux and Sequelae
    DAVID SULLIVAN HAINS; Fiscal Year: 2010
    ..These changes in DNA copy number can have profound effects on gene dosage, and alterations in DNA copy number play a key role in disease susceptibility or resistance...
  17. Let-7 miRNA control of heart development
    Cathy J Hatcher; Fiscal Year: 2010
    ..The heart is exquisitely sensitive to T-box gene dosage, and small perturbations in TBX5 expression have significant cardiac effects...
  18. Identifying and testing new targets for Parkinson Disease gene therapy
    Nicholas Muzyczka; Fiscal Year: 2013
    ..This genetic transfer system is unique in that gene dosage can be manipulated and gene expression is permanent...
  19. Hepatic Rictor Knockout Mouse Model and the Metabolic Syndrome
    JENNIFER MARIE ROJAS; Fiscal Year: 2012
    ..I will validate genetic loss of rictor in the liver, gene dosage specific effects of rictor gene expression and rictor/mTORC2 function (AKT phosphorylation)...
  20. Identify and characterize genes involved in X-chromosome inactivation
    Zhiguo Zhang; Fiscal Year: 2013
    ..inactivation (XCI), essential for female mouse development, is the molecular mechanism that ensures equivalent gene dosage of the X-linked genes between XX females and XY males...
  21. Genetic Basis of Failed Cognition in Young and Aged Mouse Models of Trisomy 21
    Eugene Yu; Fiscal Year: 2013
    ..Based on the prevailing gene dosage effect hypothesis, a cognitively relevant phenotype in DS is caused by the triplication of one or more human ..
  22. Role of PIP2 metabolism imbalance in Down Syndrome
    GILBERT DIPAOLO; Fiscal Year: 2012
    ..mice exhibit deficits in performance of the Morris water maze, suggesting that PIP2 dyshomeostasis caused by gene dosage imbalance for Synj1 may contribute to brain dysfunction and cognitive disabilities in genetic models of DS...
  23. Initiation of Epigenetic Transcriptional Regulation
    Sundeep Kalantry; Fiscal Year: 2011
    ..transcriptional inactivation of one X-chromosome in female mammals, thereby equalizing X-linked gene dosage between males and females...
  24. An Orally Delivered Hepatitis B Vaccine
    John Howard; Fiscal Year: 2009
    ..to increase expression include introgression into germplasm suited to protein accumulation, increasing gene dosage, and developing new transgenic lines incorporating an improved seed promoter, a multicopy expression unit and ..
  25. The role of Lamin B1 in myelin maintenance and demyelination
    Ying Hui Fu; Fiscal Year: 2010
    ..Patients carry an extra copy of the gene for the nuclear lamina protein, Lamin B1, resulting in increased gene dosage in ADLD brain tissue. Increased expression of Lamin B1 in Drosophila resulted in a degenerative phenotype...
  26. Molecular Mechanism of Severe Congenital Neutropenia
    H Grimes; Fiscal Year: 2009
    ..Moreover, the role of wild-type GFI1 gene dosage in controlling mutant GFI1 molecules and their mechanism of action will be discerned, then correlated to ..
  27. Gene Dosage in Mammalian Sexual Development
    ERIC J VILAIN; Fiscal Year: 2013
    ..This proposal will elucidate basic questions about how males and females become different, and will improve genetic classification and diagnostic methods of patients born with disorders of sex development. ..
  28. Quantitative Trait Genes for Circadian Phenotypes
    John R Hofstetter; Fiscal Year: 2013
    ..polymerase chain reaction (qRT-PCR);the microarray system;and a specialized cell culture system called gene dosage network analysis (GDNA)...
  29. RNAi and DNA Methylation Control Genomic Stability and Transcriptional Silencing
    JOHN KIMBLE FRAZER; Fiscal Year: 2010
    ..pombe rDNA loci, recognizing that other organisms use DNA methylation to control both genetic imprinting and gene dosage at their rDNA. Finally, we will investigate the potential link between RNAi and DNA methylation at the rDNA...
  30. Tea Modulation of Colon Carcinogenesis
    Michael Wargovich; Fiscal Year: 2013
    ..In Specific Aim 4 we will examine the chemopreventive effects of green tea/EGCG intervention on RXRa gene dosage in RXRa+/- mice with the colon carcinogen, AOM...
  31. Allelic Choice in Rett Syndrome
    Mary E Donohoe; Fiscal Year: 2013
    ..an epigenetic process that silences one of the two female X chromosomes early in development to balance the gene dosage with XY males...
  32. Neurobiological Mechanism of 15q11-13 Duplication Autism Spectrum Disorder
    Matthew P Anderson; Fiscal Year: 2010
    ..morphology will be used in our new Ube3a transgenic and existing Ube3a knockout mice to examine the effects of gene dosage on postnatal development and adult function of CA1 pyramidal neuron excitability and synaptic function (..
  33. Gene Dosage Imbalance in Neurodevelopmental Disorders
    David H Ledbetter; Fiscal Year: 2013
    ..of rare CNVs associated with neurodevelopmental disorders (hereafter referred to as IDD/ASDs), to develop a Gene Dosage Map for human development and to identify new CNVs and candidate genes responsible for these disorders with the ..
  34. Neurobiological Mechanism of 15q11-13 Duplication Autism Spectrum Disorder
    Matthew P Anderson; Fiscal Year: 2013
    ..to compare and contrast the defects in neuronal mRNA expression and circuit functions produced by altered Ube3a gene dosage that may underlie the behavioral phenotypes of Autism Spectrum Disorder (ASD) with maternal 15q11-13 ..
  35. Calcineurin/NFAT signaling in pathogenesis of neurodegeneration in Down Syndrome
    Isabella A Graef; Fiscal Year: 2013
    ..of RCAN1 and Dyrk1a and the consequent decrease of calcineurin/NFAT activity, can synergize with increased APP gene dosage and expression to enhance A[unreadable] deposition and neurofibrillary tangle formation in the CNS of DS ..
  36. Establishing zebrafish as a model for rai1 gene dosage
    James A Lister; Fiscal Year: 2010
    ..Taken together, these findings strongly suggest that gene dosage of RAI1 is critical for normal development, behavior, and growth...
  37. Genomic Organization of Recombination Hot Spots
    Kenneth Paigen; Fiscal Year: 2013
    ..locations by activating recombination there;it has no quantitative modifiers, and its role is independent of gene dosage. Here we will investigate the complementary regulatory system controlling quantitative levels of hotspot ..
  38. GENOMIC APPROACHES TO ANEUPLOIDY
    Roger H Reeves; Fiscal Year: 2013
    ..We have begun a survey of the entire Hsa21 gene set to determine gene dosage effects on early development in zebrafish...
  39. Characterization of Cardiac Progenitors Derived from 22q11-deleted Patients
    WILLIAM TSWENCHING contact PU; Fiscal Year: 2010
    ..by abnormalities of right ventricle and outflow tract development, at least in part as a result of reduced gene dosage of TBX1, a key transcriptional regulator of SHF differentiation...
  40. Dosage compensation of a novel X chromosome
    JOSEPHINE ANNA REINHARDT; Fiscal Year: 2013
    ..The proposed research will investigate whether and how gene dosage has been compensated in this species. The aims of the research are threefold...
  41. Function of Mammalian Single-minded Genes SIM1 and SIM2
    Chen Ming Fan; Fiscal Year: 2009
    ..Through the proposed research, we hope to unravel the molecular programs controlled by Sim1 and Sim2, thereby understanding the human diseases caused by the alteration of their gene dosage.
  42. ROLE OF NOTCH-EGFR PATHWAY COOPERATIVITY IN BASAL-LIKE BREAST CANCER
    LOREN SCOTT MICHEL; Fiscal Year: 2012
    ..Fortunately, many Notch-dependent processes are sensitive to gene dosage and are receptor specific...
  43. Study of ANP Receptor: Gene Targeting and Expression
    Kailash N Pandey; Fiscal Year: 2013
    ..from the above lines of investigation will provide the means to test directly the efficacy and impact of Npr1 gene dosage and null mutation on ANP/NPRA-mediated biological responses...
  44. A longitudinal study of loss of imprinting in the placenta
    Ronald Wapner; Fiscal Year: 2012
    ..of imprinting (LOI) leads to bi-allelic expression of the imprinted gene, potentially causing a doubling of gene dosage or gene dysregulation, resulting in disease...
  45. Presenilin dysfunction in the brain
    Raymond J Kelleher; Fiscal Year: 2013
    ..the defects in these processes caused by complete PS inactivation, and we will also assess the role of PS gene dosage in determining the phenotypic consequences of the mutation...
  46. Centromere identity and function
    Ben E Black; Fiscal Year: 2013
    ..results in spontaneous abortion or birth defects if it arises in the gametes and that is a major contributor to gene dosage imbalances in almost all human cancers...
  47. Generate and Characterize Knock-In Mice Harboring DRD2 Ser311Cys Polymorphism
    Ya Ping Tang; Fiscal Year: 2010
    ..In order to determine whether the gene dosage plays a role in these molecular/neuronal/behavioral responses, both homozygous and heterozygous knock-in mice ..
  48. Role of KLF2 in erythropoiesis and globin expression
    Joyce A Lloyd; Fiscal Year: 2010
    ..To study the effects of gene dosage on red cell morphology and globin gene expression, EKLF-/-KLF2 and EKLF KLF2-/- will be compared to wildtype, ..
  49. Role of 14-3-3o in development and repair of corneal epithelium
    Qiutang Li; Fiscal Year: 2013
    ..Thus, 14-3-3[unreadable] gene dosage distinguishes corneal epithelial development embryologically from corneal epithelial differentiation following ..
  50. Physiological Regulation of Proinsulin Quality and Quantity Control in the Pancre
    Douglas R Cavener; Fiscal Year: 2013
    ..In support of this assumption we have already shown that reducing Perk gene dosage in half results in reduced blood glucose levels and ameliorates the progression of diabetes of the Akita ..
  51. Pathophysiology of APP in vivo
    Hui Zheng; Fiscal Year: 2013
    ..to investigate the genetic and functional interactions of APP and ApoE, and to evaluate the effects of APP gene dosage and A[unreadable] on APP/ApoE-mediated adult neurogenesis using the APP YAC genomic transgenic mice...
  52. Alpha-Synuclein Regulation by microRNAs
    Eunsung Junn; Fiscal Year: 2013
    ..of the a-Syn gene locus is linked to dominantly inherited PD with an onset age that correlates inversely with gene dosage, transgenic animal models expressing wild-type human a-Syn manifest phenotypic changes reminiscent of this ..
  53. CDX2 TUMOR SUPPRESSOR PATHWAY DEFECTS IN COLON CANCER
    Eric R Fearon; Fiscal Year: 2013
    ..a conditional knockout of Cdx2 and have found Cdx2 inactivation in colon epithelium yields interesting gene dosage-dependent effects...
  54. Evolutionary Roles of Homozygosity &Copy Number Variation in Mental Disorders
    MATTHEW CHARLES KELLER; Fiscal Year: 2013
    ..g., resequencing) investigations of important genomic regions, and potentially informing translational research aimed at developing diagnostic tests and treatments related to gene dosage.
  55. Sexually dimorphic miR-497 regulates alpha-synuclein and alpha-synucleinopathy
    Peter T Nelson; Fiscal Year: 2013
    ..of aberrant deposits of alpha-synuclein (alpha-SN) protein and there is evidence that increased alpha-SN gene dosage is seen in some cases of DLB...
  56. Ureteric Bud Patterning
    Doris A Herzlinger; Fiscal Year: 2013
    ..in controlling ureteral smooth muscle differentiation will be analyzed in mice with a severe knockdown in Bmp4 gene dosage that supports embryonic viability to birth, but not beyond...
  57. Multi-allelic copy number variation of the human genome
    STEVEN ANDREW MCCARROLL; Fiscal Year: 2013
    ..The successful completion of this work will lead to the discovery of relationships between disease risk and gene dosage, helping to reveal the molecular etiology of human disease.
  58. Loss of EBF1 Expression: A Novel Murine Model for Human B-ALL
    Julita A Ramírez; Fiscal Year: 2013
    ..Furthermore, B cell development is impeded when Ebf1 gene dosage is reduced. Little is known regarding the potential roles of EBF1 in leukemogenesis...
  59. Regulation of Xist RNA processing in embryonic stem cells
    Barbara Panning; Fiscal Year: 2013
    ..regulated transcriptional silencing of one X chromosome in female cells, used to equalize X-linked gene dosage with male cells...
  60. Amyloid Precursor Protein and Ubiquitination
    Yuzhi Chen; Fiscal Year: 2013
    ..APP modulates Cullin5 ligase activity under physiological conditions, and further suggest that increased APP gene dosage or APP mutations may impair Cullin5 ligase functions by increasing its turnover rate and leading to decreased ..
  61. An Animal Model for Human Heart-Hand Syndromes
    Robert K Ho; Fiscal Year: 2013
    ..This proposal will determine how gene dosage affects organogenesis at the cell behavior level, especially with regards to how directional cell migrations in ..
  62. Causes and consequences of gene copy number change in adapting yeast populations
    Maitreya J Dunham; Fiscal Year: 2013
    ..related to human health, little work has been done to determine how cells adapt to such extreme changes in gene dosage. Prior work from my lab using the model eukaryote yeast has found that aneuploidy can be detrimental to cells ..
  63. MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW
    MARK STEEN; Fiscal Year: 2001
    ..Because carriers for homocystinuria caused by these enzyme deficiencies have half the normal gene dosage of either CBS or MS, they are expected to have increased tHcy either after a standard methionine load, or at ..
  64. Investigation of the Molecular Determinants of DAX-1 Mediated X-Linked Adrenal Hy
    Christina Tzagarakis Foster; Fiscal Year: 2009
    ....
  65. MERCURY RESISTANCE IN STAPHYLOCOCCUS AUREUS
    RICHARD LADDAGA; Fiscal Year: 1992
    ..S1 mapping of the 3'-end of the two pI258 mer transcripts will be done. The relationship between gene dosage and the total number of transcripts produced will also be examined...
  66. TRANSMISSIBLE AND GENETIC NEURODENGENERATIVE DISEASES
    STANLEY PRUSINER; Fiscal Year: 1999
    ..PrP have shown that long incubation times are not dominant traits but rather result from the effects of PrP gene dosage. These findings overturned one of the major tenets which were established in scrapie research over the past 25 ..
  67. MECHANISMS OF ADRENAL CORTEX GROWTH/DIFFERENTIATION
    Gary Hammer; Fiscal Year: 2000
    ..in a patient with adrenal insufficiency raises the possibility that in addition to phosphorylation, SF-1 gene dosage is critical for the adrenal developmental and steroidogenic programs...
  68. MOLECULAR GENETICS OF GENE DOSAGE COMPENSATION AND SEX
    Alan Christensen; Fiscal Year: 1991
    ..respond by hyperactivating the X chromosome at the transcriptional level to compensate for the difference in gene dosage. This project is aimed at two questions: how do male cells double the transcription rate of virtually every ..
  69. DESENSITIZATION AND DOWN REGULATION OF CALCIUM RECEPTORS
    Dolores Shoback; Fiscal Year: 2002
    ..Our studies should provide insights into mechanisms underlying CaR responsiveness in secretion and growth. ..
  70. AGING EFFECTS OF ANEUPLOIDY
    W Brown; Fiscal Year: 1980
    ..The proteins identified as mapping to chromosome 21 will be tested for gene dosage effects in monosomy 21 and trisomy 21 cells using quantitative computerized analysis...
  71. Paracrine Regulation of IGF-I in the Developing Ileum
    Phillip Gordon; Fiscal Year: 2006
    ..We will utilize a transgenic IGF-overexpressing strain to investigate the effect of gene dosage on epithelial cell migration rate, during both normal and dexamethasone-accelerated mucosal maturation...