heterozygote

Summary

Summary: An individual having different alleles at one or more loci regarding a specific character.

Top Publications

  1. ncbi Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers
    Peter C Fong
    Drug Development Unit, Royal Marsden National Health Service Foundation Trust and the Institute of Cancer Research, Sutton, Surrey, United Kingdom
    N Engl J Med 361:123-34. 2009
  2. pmc A single IGF1 allele is a major determinant of small size in dogs
    Nathan B Sutter
    National Human Genome Research Institute, Building 50, Room 5349, 50 South Drive MSC 8000, Bethesda, MD 20892 8000, USA
    Science 316:112-5. 2007
  3. ncbi Genetic structure of human populations
    Noah A Rosenberg
    Molecular and Computational Biology, 1042 West 36th Place DRB 289, University of Southern California, Los Angeles, CA 90089, USA
    Science 298:2381-5. 2002
  4. pmc Pathogenic mitochondrial DNA mutations are common in the general population
    Hannah R Elliott
    Mitochondrial Research Group, Newcastle University, Newcastle upon Tyne, UK
    Am J Hum Genet 83:254-60. 2008
  5. ncbi A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
    Y Ogura
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nature 411:603-6. 2001
  6. ncbi Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 350:1838-49. 2004
  7. ncbi Mutations in dynein link motor neuron degeneration to defects in retrograde transport
    Majid Hafezparast
    Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
    Science 300:808-12. 2003
  8. pmc Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait
    Thomas N Williams
    Kenya Medical Research Institute Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, PO Box 230, Kilifi District Hospital, Kilifi, Kenya
    Nat Genet 37:1253-7. 2005
  9. ncbi Targeted disruption of the melanocortin-4 receptor results in obesity in mice
    D Huszar
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    Cell 88:131-41. 1997
  10. pmc Out of Africa: modern human origins special feature: explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa
    Michael DeGiorgio
    Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109 2218, USA
    Proc Natl Acad Sci U S A 106:16057-62. 2009

Detail Information

Publications295 found, 100 shown here

  1. ncbi Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers
    Peter C Fong
    Drug Development Unit, Royal Marsden National Health Service Foundation Trust and the Institute of Cancer Research, Sutton, Surrey, United Kingdom
    N Engl J Med 361:123-34. 2009
    ..We conducted a clinical evaluation in humans of olaparib (AZD2281), a novel, potent, orally active PARP inhibitor...
  2. pmc A single IGF1 allele is a major determinant of small size in dogs
    Nathan B Sutter
    National Human Genome Research Institute, Building 50, Room 5349, 50 South Drive MSC 8000, Bethesda, MD 20892 8000, USA
    Science 316:112-5. 2007
    ..A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs...
  3. ncbi Genetic structure of human populations
    Noah A Rosenberg
    Molecular and Computational Biology, 1042 West 36th Place DRB 289, University of Southern California, Los Angeles, CA 90089, USA
    Science 298:2381-5. 2002
    ..General agreement of genetic and predefined populations suggests that self-reported ancestry can facilitate assessments of epidemiological risks but does not obviate the need to use genetic information in genetic association studies...
  4. pmc Pathogenic mitochondrial DNA mutations are common in the general population
    Hannah R Elliott
    Mitochondrial Research Group, Newcastle University, Newcastle upon Tyne, UK
    Am J Hum Genet 83:254-60. 2008
    ..The exclusive detection of m.14484T-->C on haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission...
  5. ncbi A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
    Y Ogura
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nature 411:603-6. 2001
    ..These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease...
  6. ncbi Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 350:1838-49. 2004
    ..2 subunit of this channel (KCNJ11) cause neonatal diabetes...
  7. ncbi Mutations in dynein link motor neuron degeneration to defects in retrograde transport
    Majid Hafezparast
    Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
    Science 300:808-12. 2003
    ..These mutations exclusively perturb neuron-specific functions of dynein...
  8. pmc Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait
    Thomas N Williams
    Kenya Medical Research Institute Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, PO Box 230, Kilifi District Hospital, Kilifi, Kenya
    Nat Genet 37:1253-7. 2005
    ..Negative epistasis could explain the failure of alpha(+)-thalassemia to reach fixation in any population in sub-Saharan Africa...
  9. ncbi Targeted disruption of the melanocortin-4 receptor results in obesity in mice
    D Huszar
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    Cell 88:131-41. 1997
    ..Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R...
  10. pmc Out of Africa: modern human origins special feature: explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa
    Michael DeGiorgio
    Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109 2218, USA
    Proc Natl Acad Sci U S A 106:16057-62. 2009
    ....
  11. pmc mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells
    Mirei Murakami
    Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630 0192, Japan
    Mol Cell Biol 24:6710-8. 2004
    ..These data show that mTOR controls both cell size and proliferation in early mouse embryos and embryonic stem cells...
  12. pmc Genetic variation and population structure in native Americans
    Sijia Wang
    The Galton Laboratory, Department of Biology, University College London, London, United Kingdom
    PLoS Genet 3:e185. 2007
    ..These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas...
  13. pmc Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies
    A Antoniou
    Cancer Research U K Genetic Epidemiology Unit, Department of Public Health, University of Cambridge, Cambridge, United Kingdom
    Am J Hum Genet 72:1117-30. 2003
    ..The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers...
  14. ncbi SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes
    Marina A Bellani
    Genetics and Biochemistry Branch, NIDDK, NIH, Bethesda, MD 20892, USA
    J Cell Sci 118:3233-45. 2005
    ....
  15. pmc Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development
    Yann Gaël Gangloff
    Genome Research Institute, University of Cincinnati, 2180 E Galbraith Rd, Cincinnati, OH 45237, USA
    Mol Cell Biol 24:9508-16. 2004
    ..Moreover, mTOR(-/-) embryos display a lesion in inner cell mass proliferation, consistent with the inability to establish embryonic stem cells from mTOR(-/-) embryos...
  16. pmc Short telomeres are a risk factor for idiopathic pulmonary fibrosis
    Jonathan K Alder
    Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 105:13051-6. 2008
    ..The clustering of cryptogenic liver cirrhosis with IPF suggests that the telomere shortening we identify has consequences and can contribute to what appears clinically as idiopathic progressive organ failure in the lung and the liver...
  17. ncbi Telomerase mutations in families with idiopathic pulmonary fibrosis
    Mary Y Armanios
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    N Engl J Med 356:1317-26. 2007
    ....
  18. ncbi The flowering gene SINGLE FLOWER TRUSS drives heterosis for yield in tomato
    Uri Krieger
    Institute of Plant Sciences, The Hebrew University of Jerusalem Faculty of Agriculture, Rehovot, Israel
    Nat Genet 42:459-63. 2010
    ..Our findings provide the first example of a single overdominant gene for yield and suggest that single heterozygous mutations may improve productivity in other agricultural organisms...
  19. pmc A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs
    Dana S Mosher
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 3:e79. 2007
    ..3619; p approximately 0.00028). These results highlight the utility of performance-enhancing polymorphisms, marking the first time a mutation in MSTN has been quantitatively linked to increased athletic performance...
  20. ncbi A quantitative review of heterozygosity-fitness correlations in animal populations
    J R Chapman
    Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK
    Mol Ecol 18:2746-65. 2009
    ....
  21. ncbi Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1
    Y Xue
    The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609 1500, USA
    Hum Mol Genet 8:723-30. 1999
    ..These results establish the phenotype of Cm /+ mice as a contiguous gene deletion syndrome and demonstrate that Jag1 is essential for remodeling of the embryonic vasculature...
  22. ncbi Disruption of imprinting caused by deletion of the H19 gene region in mice
    P A Leighton
    Howard Hughes Medical Institute, Princeton University, New Jersey 08544, USA
    Nature 375:34-9. 1995
    ..The somatic overgrowth of heterozygotes for the maternal deletion is attributed to a gain of function of insulin-like growth factor 2, rather than a loss of function of H19...
  23. ncbi Genetic compatibility, mate choice and patterns of parentage: invited review
    T Tregenza
    Ecology and Evolution Group, School of Biology, University of Leeds, UK
    Mol Ecol 9:1013-27. 2000
    ..This may reflect limitations in the potential for the evolution of mate choice for genetic compatibility within populations, although the most promising sources of such incompatibilities have received relatively little research...
  24. pmc Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia
    Eric M Reiman
    Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006, USA
    Proc Natl Acad Sci U S A 101:284-9. 2004
    ..Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia...
  25. pmc Geography predicts neutral genetic diversity of human populations
    Franck Prugnolle
    Theoretical and Molecular Population Genetics Group, Department of Genetics, University of Cambridge, Downing St, Cambridge CB2 3EH, UK
    Curr Biol 15:R159-60. 2005
  26. pmc Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)
    D Woodrow Benson
    Department of Pediatrics, Cincinnati Children s Hospital, Ohio, USA
    J Clin Invest 112:1019-28. 2003
    ..Our findings reveal a molecular basis for some forms of congenital SSS and define a recessive disorder of a human heart voltage-gated sodium channel...
  27. ncbi High-resolution DNA melting analysis: advancements and limitations
    Carl T Wittwer
    Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
    Hum Mutat 30:857-9. 2009
    ..of a saturating dye before PCR followed by rapid melting analysis of the PCR products, the sensitivity of heterozygote scanning approaches 100%...
  28. ncbi Identification of SLC39A4, a gene involved in acrodermatitis enteropathica
    Sebastien Kury
    Laboratoire d Etude du Polymorphisme de l ADN, Faculte de Medecine, 1 rue Gaston Veil, 44035 Nantes Cedex, France
    Nat Genet 31:239-40. 2002
    ..The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition...
  29. ncbi Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging
    Holly Van Remmen
    Department of Cellular and Structural Biology at the University of Texas Health Science Center at San Antonio, San Antonio 78229 3900, USA
    Physiol Genomics 16:29-37. 2003
    ..Thus life-long reduction of MnSOD activity leads to increased levels of oxidative damage to DNA and increased cancer incidence but does not appear to affect aging...
  30. ncbi Heterozygosity-fitness correlations: a time for reappraisal
    Marta Szulkin
    Department of Zoology, Edward Grey Institute, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom
    Evolution 64:1202-17. 2010
    ..We provide guidelines to safely interpret and quantify HFCs, and present how HFCs can be used to quantify inbreeding load and unravel the structure of natural populations...
  31. ncbi Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
    Avshalom Caspi
    Medical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King s College London, PO80 De Crespigny Park, London, SE5 8AF, UK
    Science 301:386-9. 2003
    ..This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup...
  32. ncbi Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews
    Judith Aharon-Peretz
    Department of Neurology and the Cognitive Neurology Unit, Rambam Medical Center, Haifa, Israel
    N Engl J Med 351:1972-7. 2004
    ..We examined whether mutations in the GBA gene are relevant to idiopathic Parkinson's disease...
  33. pmc Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect
    Richard J Caselli
    Department of Neurology, Mayo Clinic Arizona, Scottsdale, Arizona 85259, USA
    N Engl J Med 361:255-63. 2009
    ..The age at which memory decline diverges among persons who are homozygous for the APOE epsilon4 allele, those who are heterozygous for the allele, and noncarriers is unknown...
  34. pmc Single-locus heterotic effects and dominance by dominance interactions can adequately explain the genetic basis of heterosis in an elite rice hybrid
    Jinping Hua
    National Key Laboratory of Crop Improvement and National Center of Crop Molecular Breeding, Huazhong Agricultural University, Wuhan 430070, China
    Proc Natl Acad Sci U S A 100:2574-9. 2003
    ..These results may help reconcile the century-long debate concerning the genetic basis of heterosis...
  35. pmc Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction
    Antonis C Antoniou
    Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
    Cancer Res 70:9742-54. 2010
    ..Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers...
  36. ncbi A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C
    E Verpy
    Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, Paris Cedex 15, France
    Nat Genet 26:51-5. 2000
    ..As several of these transcripts were absent from the eye, we propose that USH1C also underlies the DFNB18 form of isolated deafness...
  37. ncbi Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy
    Albena Jordanova
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium
    Nat Genet 38:197-202. 2006
    ..YARS is the second aminoacyl-tRNA synthetase found to be involved in CMT, thereby linking protein-synthesizing complexes with neurodegeneration...
  38. ncbi A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia
    Mourad Toporsian
    Cancer Research Program, Hospital for Sick Children, Toronto, Ontario, Canada
    Circ Res 96:684-92. 2005
    ....
  39. pmc Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
    Antonis C Antoniou
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK
    Breast Cancer Res 14:R33. 2012
    ..2)...
  40. ncbi GATA4 loss-of-function mutations in familial atrial fibrillation
    Yi qing Yang
    Department of Cardiovascular Research, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, PR China
    Clin Chim Acta 412:1825-30. 2011
    ..Growing studies demonstrate that genetic defects play pivotal roles in a subgroup of AF. However, AF is a genetically heterogeneous disorder and the molecular basis of AF in a majority of cases remains unknown...
  41. pmc Major histocompatibility complex (MHC) heterozygote superiority to natural multi-parasite infections in the water vole (Arvicola terrestris)
    M K Oliver
    Institute of Biological and Environmental Sciences, University of Aberdeen, Zoology Building, Aberdeen AB24 2TZ, UK
    Proc Biol Sci 276:1119-28. 2009
    ..Two hypotheses have been proposed: overdominance (or heterozygote superiority) and negative frequency-dependent selection...
  42. pmc A high quality draft consensus sequence of the genome of a heterozygous grapevine variety
    Riccardo Velasco
    IASMA Research Center, San Michele all Adige, Trento, Italy
    PLoS ONE 2:e1326. 2007
    ..In this paper a high quality draft genome sequence of a cultivated clone of V. vinifera Pinot Noir is presented...
  43. ncbi Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2
    Mary Claire King
    Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Science 302:643-6. 2003
    ..Lifetime risks of ovarian cancer were 54% for BRCA1 and 23% for BRCA2 mutation carriers. Physical exercise and lack of obesity in adolescence were associated with significantly delayed breast cancer onset...
  44. ncbi Consequences of lack of beta 1 integrin gene expression in mice
    R Fassler
    Max Planck Institut fur Biochemie, Martinsried, Germany
    Genes Dev 9:1896-908. 1995
    ..Also, tissues derived from the neural crest contained beta 1 integrin-deficient cells indicating that migration of neuronal cells as well as neural crest cells can occur in the absence of beta 1 integrins...
  45. ncbi Impaired impulse propagation in Scn5a-knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging
    Toon A B van Veen
    Heart Lung Center, Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands
    Circulation 112:1927-35. 2005
    ..The SCN5A sodium channel is a major determinant for cardiac impulse propagation. We used epicardial mapping of the atria, ventricles, and septae to investigate conduction velocity (CV) in Scn5a heterozygous young and old mice...
  46. pmc Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers
    Susan J Ramus
    Department of Gynaecological Oncology, UCL EGA Institute for Women s Health, University College London, London, UK
    J Natl Cancer Inst 103:105-16. 2011
    ..We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2...
  47. pmc Synaptic E3 ligase SCRAPPER in contextual fear conditioning: extensive behavioral phenotyping of Scrapper heterozygote and overexpressing mutant mice
    Ikuko Yao
    Department of Medical Chemistry, Kansai Medical University, Moriguchi, Osaka, Japan
    PLoS ONE 6:e17317. 2011
    ..The behavioral phenotypes of Scrapper mutant mice suggest that molecular degradation conferred by SCRAPPER play important roles in hippocampal-dependent fear memory formation...
  48. ncbi Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer
    William D Foulkes
    Program in Cancer Genetics, Department of Oncology and Human Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
    J Natl Cancer Inst 95:1482-5. 2003
    ..0, 95% confidence interval = 1.9 to 43; P =.002, two-sided Fisher's exact test). Thus, germline BRCA1 mutations appear to be associated with a distinctive breast cancer phenotype...
  49. pmc Apolipoprotein E variation at the sequence haplotype level: implications for the origin and maintenance of a major human polymorphism
    S M Fullerton
    Institute of Molecular Evolutionary Genetics, Department of Biology, and Department of Anthropology, Pennsylvania State University, University Park, PA 16802, USA
    Am J Hum Genet 67:881-900. 2000
    ....
  50. pmc Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
    Antonis C Antoniou
    Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
    Hum Mol Genet 20:3304-21. 2011
    ..27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women...
  51. ncbi Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination
    Corinna Lappe-Siefke
    Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D 37075 Goettingen, Germany
    Nat Genet 33:366-74. 2003
    ..Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss...
  52. pmc Dominance and the evolutionary accumulation of cis- and trans-effects on gene expression
    Bernardo Lemos
    Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 105:14471-6. 2008
    ..We suggest that widespread regulatory effects of recessive low-frequency homozygous variation may provide a general mechanism mediating disease phenotypes and the genetic load of natural populations...
  53. pmc Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote
    Zhenze Zhao
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, TX 75390, USA
    Am J Hum Genet 79:514-23. 2006
    ..This healthy, fertile college graduate, who was a compound heterozygote for two inactivating mutations in PCSK9, had a strikingly low plasma level of LDL-C (14 mg/dL)...
  54. pmc P53 germline mutations in childhood cancers and cancer risk for carrier individuals
    A Chompret
    , Institute Gustave Roussy, Villejuif, France
    Br J Cancer 82:1932-7. 2000
    ..The risk of cancer associated with such mutations is very high and no evidence of low penetrance mutation was found. These mutations are frequently inherited but de novo mutations are not rare...
  55. pmc Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers
    Antonis C Antoniou
    Department of Public Health and Primary Care, Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK
    Hum Mol Genet 18:4442-56. 2009
    ..There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not...
  56. pmc Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy
    Heather M McLaughlin
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Am J Hum Genet 87:560-6. 2010
    ..Based on these data, KARS becomes the fourth ARS gene associated with CMT disease, indicating that this family of enzymes is specifically critical for axon function...
  57. ncbi Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model
    S E Gabriel
    Department of Medicine, University of North Carolina, Chapel Hill 27599
    Science 266:107-9. 1994
    ....
  58. pmc Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2
    Anna Marie Mulligan
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Worts Causeway, Cambridge, CB1 8RN, UK
    Breast Cancer Res 13:R110. 2011
    ..It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour...
  59. pmc Extreme genomic variation in a natural population
    Kerrin S Small
    Departments of Genetics and Pathology, Stanford University Medical Center, Stanford, CA 94305 5324, USA
    Proc Natl Acad Sci U S A 104:5698-703. 2007
    ..These results constitute in-depth insight into the dynamics of highly polymorphic genomes and provide important empirical support of population genetic theory as it pertains to population size, heterozygosity, and natural selection...
  60. pmc Oligogenic basis of isolated gonadotropin-releasing hormone deficiency
    Gerasimos P Sykiotis
    Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 107:15140-4. 2010
    ....
  61. pmc Inherited haemoglobin disorders: an increasing global health problem
    D J Weatherall
    Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, England
    Bull World Health Organ 79:704-12. 2001
    ....
  62. ncbi GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo
    Yuzhen Zhang
    Department of Medicine and University of Pennsylvania, Philadelphia, PA 19104, USA
    Development 134:189-98. 2007
    ....
  63. ncbi Adult-onset primary open-angle glaucoma caused by mutations in optineurin
    Tayebeh Rezaie
    Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA
    Science 295:1077-9. 2002
    ..Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role...
  64. ncbi A novel mutation in the GATA4 gene in patients with Tetralogy of Fallot
    Georges Nemer
    Department of Biochemistry, American University of Beirut, Beirut, Lebanon
    Hum Mutat 27:293-4. 2006
    ....
  65. ncbi X-inactivation profile reveals extensive variability in X-linked gene expression in females
    Laura Carrel
    Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Nature 434:400-4. 2005
    ..This suggests a remarkable and previously unsuspected degree of expression heterogeneity among females...
  66. ncbi Relative frequency and morphology of cancers in carriers of germline TP53 mutations
    J M Birch
    CRC Paediatric and Familial Cancer Research Group and Department of Pathology, Royal Manchester Children s Hospital, Stancliffe, Hospital Road, Manchester M27 4HA, UK
    Oncogene 20:4621-8. 2001
    ..We conclude that germline TP53 mutations do not simply increase general cancer risk. There are tissue-specific effects...
  67. ncbi Reduced angiogenic responses in adult Endoglin heterozygous mice
    Mirjana Jerkic
    Instituto Reina Sofia de Investigacion Nefrologica, Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, 37007 Salamanca, Spain
    Cardiovasc Res 69:845-54. 2006
    ..To determine if angiogenesis is altered in adult Endoglin heterozygous (Eng(+/-)) mice, the animal model for the vascular disorder hereditary hemorrhagic telangiectasia type 1 (HHT1)...
  68. ncbi Historical habitat connectivity affects current genetic structure in a grassland species
    Z Munzbergova
    Institute of Botany, Academy of Sciences of the Czech Republic, Pruhonice, Czech Republic
    Plant Biol (Stuttg) 15:195-202. 2013
    ..In both cases, the oldest time layer (1850) was the most informative. Most populations showed heterozygote excess, indicating disequilibrium due to recent gene flow or selection against homozygotes...
  69. pmc The course of malaria in mice: major histocompatibility complex (MHC) effects, but no general MHC heterozygote advantage in single-strain infections
    Claus Wedekind
    Zoological Institute, Division of Conservation Biology, University of Bern, 3012 Bern, Switzerland
    Genetics 170:1427-30. 2005
    A general MHC-heterozygote advantage in parasite-infected organisms is often assumed, although there is little experimental evidence for this...
  70. pmc A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice
    Andreas Greth
    The Menzies Research Institute of Tasmania, University of Tasmania, Hobart, Australia
    PLoS ONE 7:e38999. 2012
    ..05). We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites...
  71. ncbi Premutation and intermediate-size FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles
    C Dombrowski
    Unite de Recherche en Genetique Humaine et Moleculaire, Hospital St François d Assise Research Center, Department of Medical Biology, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada, G1L 3L5
    Hum Mol Genet 11:371-8. 2002
    ..The loss of AGG interruptions thus appears to be a late event that leads to greatly increased instability and may be related to the haplotype background of specific FMR1 alleles...
  72. ncbi CDC4/FBXW7 and the 'just enough' model of tumourigenesis
    Hayley Davis
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
    J Pathol 227:131-5. 2012
    ..For FBXW7 mutations that occur away from the propellor tips, the heterozygote may have some effect on tumourigenesis, but there is selective pressure for a 'second hit'...
  73. ncbi Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy
    Daniela Hauer
    Departments of Anaesthesiology, Ludwig Maximilians University, Munich, Germany
    Crit Care Med 39:643-50. 2011
    ....
  74. pmc High degree of sex chromosome differentiation in stickleback fishes
    Takahito Shikano
    Ecological Genetics Research Unit, Department of Biosciences, University of Helsinki, P O Box 65, FI 00014, Helsinki, Finland
    BMC Genomics 12:474. 2011
    ....
  75. pmc A new highly penetrant form of obesity due to deletions on chromosome 16p11.2
    R G Walters
    Section of Genomic Medicine, Imperial College London, London W12 0NN, UK
    Nature 463:671-5. 2010
    ..3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts...
  76. pmc Congenital hyperinsulinism and glucose hypersensitivity in homozygous and heterozygous carriers of Kir6.2 (KCNJ11) mutation V290M mutation: K(ATP) channel inactivation mechanism and clinical management
    Karen J Loechner
    Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, USA
    Diabetes 60:209-17. 2011
    ..In this study, we sought to identify the mechanistic basis of K(ATP)-induced HI in two probands and to characterize the clinical course...
  77. pmc Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome
    Sheila Santin
    Fundacio Puigvert, Cartagena 340 350, 08025 Barcelona, Spain
    Clin J Am Soc Nephrol 6:344-54. 2011
    ..To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation...
  78. ncbi Synaptic vesicle recycling is enhanced by torsinA that harbors the DYT1 dystonia mutation
    Yasuhiro Kakazu
    Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
    Synapse 66:453-64. 2012
    ..They also indicate that this regulation is influenced by neuronal activity, further supporting the idea that synaptic abnormalities contribute to the pathophysiology of DYT1 dystonia...
  79. ncbi Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer
    Ferdinandos Skoulidis
    Department of Oncology and The Medical Research Council Cancer Cell Unit, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK
    Cancer Cell 18:499-509. 2010
    ..We suggest a revised model for tumor suppression by BRCA2 with implications for the therapeutic strategy targeting BRCA2 mutant cancer cells...
  80. pmc Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
    Susan J Ramus
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, California, USA
    Hum Mutat 33:690-702. 2012
    ..The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer...
  81. ncbi Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia
    Shinji Kunishima
    Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, 4 1 1 Sannomaru, Naka ku, Nagoya, Japan
    Blood 117:5479-84. 2011
    ..We propose that activating mutations in ITGA2B and ITGB3 represent the etiology of a subset of congenital macrothrombocytopenias...
  82. ncbi Identification of deletions and duplications of the DMD gene in affected males and carrier females by multiple ligation probe amplification (MLPA)
    Valentina Gatta
    Department of Biomedical Sciences, G d Annunzio University Foundation, Chieti, Italy
    Hum Genet 117:92-8. 2005
    ....
  83. ncbi The interleukin-6 gene -572C/G promoter polymorphism modifies Alzheimer's risk in APOE epsilon 4 carriers
    Min Wang
    Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, PR China
    Neurosci Lett 482:260-3. 2010
    ..301-fold (Wald=11.093, adjust OR=3.301, 95% CI=1.635-6.665, P=0.001) compared to CG+GG genotype. The present results suggest the -572 polymorphism could modify the risk for SAD in APOE epsilon 4 carriers...
  84. pmc Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study
    F Demenais
    INSERM U946, Fondation Jean Dausset CEPH, 27 rue Juliette Dodu, 75010 Paris, France
    J Natl Cancer Inst 102:1568-83. 2010
    ..However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited...
  85. ncbi Natural selection coupled with intragenic recombination shapes diversity patterns in the major histocompatibility complex class II genes of the giant panda
    Yi Yan Chen
    College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People s Republic of China
    J Exp Zool B Mol Dev Evol 314:208-23. 2010
    ..Collectively, these findings indicate that natural selection accompanied by recombination drives the contrasting diversity patterns of the MHC class II genes between the two studied subspecies of giant panda...
  86. pmc Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans
    Zheng Li
    University College London UCL Institute of Ophthalmology, London EC1V 9EL, UK
    Am J Hum Genet 85:711-9. 2009
    ..These findings suggest an important role of this specific cation channel for the normal function of ON bipolar cells in the human retina...
  87. pmc X-inactivation modifies disease severity in female carriers of murine X-linked Alport syndrome
    Michelle N Rheault
    Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
    Nephrol Dial Transplant 25:764-9. 2010
    ..X-inactivation, the method by which females (XX) silence transcription from one X chromosome in order to achieve gene dosage parity with males (XY), likely modifies the carrier phenotype, but this hypothesis has not been tested directly...
  88. ncbi Genetic map of artichoke × wild cardoon: toward a consensus map for Cynara cardunculus
    Gabriella Sonnante
    Institute of Plant Genetics, National Research Council, Via Amendola, 165 A, 70126, Bari, Italy
    Theor Appl Genet 123:1215-29. 2011
    ..The establishment of a consensus map represents a necessary condition to plan a complete sequencing of the globe artichoke genome...
  89. ncbi Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice
    S Forss-Petter
    Institute of Neurology, University of Vienna, Austria
    J Neurosci Res 50:829-43. 1997
    ..This suggests that additional genetic or environmental conditions must be fulfilled to model the early-onset and lethality of cerebral ALD in transgenic mice...
  90. ncbi Genome-wide single nucleotide polymorphism analysis reveals recent genetic introgression from domestic pigs into Northwest European wild boar populations
    D J Goedbloed
    Resource Ecology Group, Wageningen UR, Wageningen, The Netherlands
    Mol Ecol 22:856-66. 2013
    ....
  91. pmc Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia
    Taneli Raivio
    Children s Hospital, Helsinki University Central Hospital, Institute of Biomedicine Physiology, University of Helsinki 00290 Helsinki, Finland
    J Clin Endocrinol Metab 97:E694-9. 2012
    ..Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain...
  92. pmc GJB2 mutations and degree of hearing loss: a multicenter study
    Rikkert L Snoeckx
    Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
    Am J Hum Genet 77:945-57. 2005
    ..Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes...
  93. ncbi Fundus albipunctatus associated with compound heterozygous mutations in RPE65
    Patrik Schatz
    Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark
    Ophthalmology 118:888-94. 2011
    ..To describe a family with an 18-year-old woman with fundus albipunctatus and compound heterozygous mutations in RPE65 whose unaffected parents and 1 female sibling harbored single heterozygous RPE65 mutations...
  94. ncbi Use of single nucleotide polymorphism microarrays to distinguish between balanced and normal chromosomes in embryos from a translocation carrier
    Nathan R Treff
    Reproductive Medicine Associates of New Jersey Research, 111 Madison Avenue, Suite 100, Morristown, NJ 07960, USA
    Fertil Steril 96:e58-65. 2011
    ..To prove the ability to distinguish between balanced and normal chromosomes in embryos from a translocation carrier...
  95. ncbi Two novel mutations in surfactant protein-C, lung function and obstructive lung disease
    Marie Baekvad-Hansen
    Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, Herlev Ringvej 75, DK 2730 Herlev, Copenhagen, Denmark
    Respir Med 104:418-25. 2010
    ..A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma...
  96. pmc Mutation analysis of 12 genes in Chinese families with congenital cataracts
    Wenmin Sun
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat Sen University, Guangzhou, China
    Mol Vis 17:2197-206. 2011
    ..To identify mutations in 12 genes in Chinese families with congenital cataracts...
  97. ncbi MHC heterozygosity and survival in red junglefowl
    Kirsty Worley
    School of Biological Sciences, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK
    Mol Ecol 19:3064-75. 2010
    ..Although the exact nature of selection remains unclear, three main hypotheses have been put forward; heterozygote advantage, negative frequency-dependence and fluctuating selection...
  98. pmc Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice: a role for glucagon action in pregnancy maintenance
    Sophia Ouhilal
    Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY 10467, USA
    Am J Physiol Endocrinol Metab 302:E522-31. 2012
    ..Our data suggest that, similarly to insulin, glucagon action contributes to normal female reproductive function...
  99. pmc Homozygous and heterozygous p53 knockout rats develop metastasizing sarcomas with high frequency
    Ruben van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    Am J Pathol 179:1616-22. 2011
    ..These unique features make this rat highly complementary to other rodent p53 knockout models and a versatile tool for investigating tumorigenesis processes as well as genotoxic studies...
  100. ncbi Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations
    Hanne Meijers-Heijboer
    Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
    Nat Genet 31:55-9. 2002
    ....
  101. ncbi Novel GATA4 mutations in lone atrial fibrillation
    Jin qi Jiang
    Department of Emergency, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200030, PR China
    Int J Mol Med 28:1025-32. 2011
    ..The findings expand the mutation spectrum of GATA4 linked to AF and provide novel insight into the molecular mechanism involved in the pathogenesis of AF...

Research Grants64

  1. The genetics and pathophysiology of impaired Wnt signaling in metabolic syndrome
    Arya Mani; Fiscal Year: 2012
    ..Preliminary results from IPGTT in heterozygote knockout mice on Western diet has demonstrated increased glucose stimulated insulin levels and reduced hepatic ..
  2. The function of ATM protein in the biology of the adult neuron CNS:
    Karl Herrup; Fiscal Year: 2013
    ..will be followed by in vivo trials comparing wild type with two different Atm mutations and their compound heterozygote. In a final series of pilot experiments we will explore whether ATM malfunction plays a role in other ..
  3. Role of troponin T isoforms in nemaline myopathy
    Jian Ping Jin; Fiscal Year: 2012
    ..We shall investigate the potential effect of half dosage of slow TnT gene on muscle function in heterozygote slow TnT knock-in mutant mice. Non-myofilament-associated TnT fragments exhibit cytotoxicity...
  4. Dopamine D1 Receptor in mouse models of primary dystonia
    Laurie J Ozelius; Fiscal Year: 2013
    ..effects and compensatory maladaptations in neurotransmission, particularly dopaminergic and adenosinergic, Gnal heterozygote-null mice will offer clues to pathophysiology in DYT1 (TOR1A) and DYT6 (THAP1) EOTD as well...
  5. Effects of nerve demyelination on auditory synaptic functions
    Jun Hee Kim; Fiscal Year: 2012
    ..of neural tissue obtained from the LES pups that show a severe behavior phenotype (homozygote) or are normal (heterozygote)...
  6. Brain interleukin-18 control of food intake and energy expenditure
    Eric P Zorrilla; Fiscal Year: 2013
    ..Because heterozygote IL-18+/- mutant mice show an intermediate hyperphagic phenotype, the findings appear to be regulatory, rather ..
  7. Redox Regulation of SERCA by Nitric Oxide
    Richard A Cohen; Fiscal Year: 2013
    ..state of SERCA C674, 2) a sequence-specific antibody that recognizes irreversibly oxidized SERCA C674, and 3) heterozygote SERCA2 C674S knock-in (SKI+/-) mice that preliminary studies show have abnormal 7NO-stimulated SERCA activity ..
  8. BDNF-Estrogen Interactions with Perimenopausal Mood and Cognition
    Elizabeth M Waters; Fiscal Year: 2012
    ..menopause through gradual ovarian cessation now allows for the replication of the perimenopausal period in heterozygote Val66Met mice...
  9. Mechanism of Vascular Remodeling in Hyperhomocysteinemia
    Suresh C Tyagi; Fiscal Year: 2010
    ..The PPARy agonist, ciglitazone will be administered to wild type (WT), cystathione (3 synthase (CBS) knockout heterozygote and homozygote (i.e...
  10. FAH-Deficient Pigs
    Scott L Nyberg; Fiscal Year: 2011
    ..With regard to commercialization of this novel technology, we have already produced Fah-null heterozygote female pigs by rAAVdj and SCNT methodology...
  11. Implications of Endothelial-Myocyte Uncoupling in Cardiac Arrhythmia
    Suresh C Tyagi; Fiscal Year: 2010
    ..CBS heterozygote (-/+) knockout (CBSKO) mice will be crossbred with iNOS homozygote (-/-) knockout (iNOSKO) mice, producing wild ..
  12. Titin Splicing Mechanisms and Physical Implications
    Marion L Greaser; Fiscal Year: 2010
    ..Experiments where the titin stretch signals can be balance using heterozygote mutants and a model system where titin expression is altered by propylthiouricil will be conducted...
  13. Serum Biomarkers Associated With Phenotypic Expression of Hemochromatosis.
    Kris Kowdley; Fiscal Year: 2013
    ..is one of the most common inherited diseases among Caucasians with an estimated prevalence of 1 in 250 and a heterozygote carrier rate of 8%[unreadable]10% in the white population...
  14. Aldosterone, Histone Demethylase and Cardiovascular Disease
    Gordon H Williams; Fiscal Year: 2010
    ..and in vitro studies on vessels and adrenals in both humans (from our HyperPATH cohort) and animals (the LSD1 heterozygote knockout mouse where the LSD1 levels are 50% of that in the wild type)...
  15. Ednrb Regulation of Gastrointestinal Motility
    KENT CHARLES WILLIAMS; Fiscal Year: 2013
    ..proposed: Aim 1 will compare the structure and function of the ENS in the small intestine between homozygote, heterozygote, and wildtype Ednrb mouse littermates...
  16. A20 Gene Polymorphisms in LDLT
    Christiane Ferran; Fiscal Year: 2012
    ..Indeed, we showed that partial A20 knockdown, as seen in heterozygote mice (A20 ) significantly impairs liver regeneration and increases lethality following 2/3 partial hepatectomy...
  17. Epigenetic Regulation of Heterochromatin Condensation in Huntington's Disease
    Hoon Ryu; Fiscal Year: 2013
    ..Specific Aim 3: To cross mice genetically deficient in CBP (heterozygote and knockout) and ESET transgenic mice with the HD mice to determine the relationship among alterations of HMT ..
  18. PATHOGENESIS OF DIABETIC NEPHROPATHY
    Yashpal S Kanwar; Fiscal Year: 2013
    ..to amelioration in renal dysfunctions and progression to tubulo-interstitial injury in STZ-induced diabetes in heterozygote (+/-) mice and when the mutant Null (-/-) mice are cross bred with Akita mice...
  19. Microvascular Endothelial Cells in the Pathogenesis of Chronic Kidney Injury
    Ikuyo Yamaguchi; Fiscal Year: 2011
    ..UUO studies will use VE-cadherin heterozygote () mice and small interfering RNA (siRNA) to investigate how the level of VE-cadherin expression affects the ..
  20. Genetic analysis of a spontaneous mutation in a rat with a novel hind limb defect
    Debasish Sinha; Fiscal Year: 2010
    ..Carrying the line was complicated by the absence of a heterozygote phenotype...
  21. Fas pathway in organ-specific tolerance and autoimmunity
    ABDEL HAMAD; Fiscal Year: 2010
    ..Our preliminary data strongly support this hypothesis as we found that mice bearing heterozygote gld mutation (NOD-gld/+ mice) are protected from diabetes without developing lymphoproliferation indicating ..
  22. Intestinal Biotin Absorption: Physiological, Cellular and Molecular Aspects
    Hamid M Said; Fiscal Year: 2013
    ..preliminary studies aimed at generating conditional SMVT deficient (knockout) mice, we have already generated heterozygote Slc5a6 loxP mice and are currently using them to generating homozygous Slc5a6 loxP mice that will then use to ..
  23. Manganese Superoxide Dismutase and Renal Ischemia/Reperfusion
    LEE A MACMILLAN-CROW; Fiscal Year: 2013
    ..Conversely, compelling new data show that downregulation of MnSOD (using MnSOD heterozygote (-/+) transgenic mice) results in augmentation of mitochondrial and renal injury...
  24. Exploring Kabuki Syndrome as a Treatable Cause of Intellectual Disability
    Hans Tomas Bjornsson; Fiscal Year: 2013
    ..e. histone H3K4 trimethylation and histone acetylation);(b) exploring whether the double heterozygote state (Mll2+/- and Cbp+/-) increases the severity of the abnormalities found in Mll2 (+/-);(c) testing the ..
  25. Mechanisms of Genetic Seizure Susceptibility in Juvenile Myoclonic Epilepsy
    David A Greenberg; Fiscal Year: 2012
    ..The knockout data show that absence of BRD2 is incompatible with life. In heterozygote knockout mice (Brd2), the neural substrate is altered: there is a deficit of inhibitory neurons in two brain ..
  26. GENETIC BASIS OF DIETARY OBESITY IN MICE
    James M Cheverud; Fiscal Year: 2010
    ..This hypothesis will be tested using a quantitative hybrid complementation test where an AI Line heterozygote for the locus in question is crossed with a strain in which the gene of interest is knocked-out...
  27. Molecular Mechanism of Akirin Function During Myogenesis
    SCOTT JAMES NOWAK; Fiscal Year: 2013
    ..Second, we will use a double heterozygote assay to identify candidate proteins that interact with Akirin during muscle development, and are essential ..
  28. Statistical and Computational Tools for Next-generation ChIP-seq Applications
    Hongkai Ji; Fiscal Year: 2013
    ..transcription factors (TFs), and (3) how to analyze allele-specific events given the small amount of data at heterozygote SNPs which cause low statistical power...
  29. Mechanisms of Homocysteine-Induced Fibrinogen-Amyloid Plaque Formation
    Suresh C Tyagi; Fiscal Year: 2013
    ..complex formation, the studies will be done on pial vessels of wild type (WT), Cystathionine b-Synthase heterozygote (CBS+/-) mice (a model of HHcy), MMP-9 gene knockout (MMP9-/-), CBS and MMP-9 double knockout (CBS+/-/MMP9-/-), ..
  30. Testing mechanisms of parasite-mediated selection on MHC genetic diversity
    JILLIAN TIKKA DETWILER; Fiscal Year: 2013
    ..of these studies have difficulty differentiating between the three hypotheses of parasite-mediated selection: heterozygote advantage, rare-allele advantage, and fluctuating selection...
  31. GENETICS OF NICOTINE TOLERANCE: ROLE OF RECEPTORS
    Michael J Marks; Fiscal Year: 2013
    ..Response of [unreadable]5 and [unreadable]4 null mutant and heterozygote mice will be compared to that of wild-type mice...
  32. Ku70 Binding Protein-5 (KUB5), a Novel Factor in Nonhomologous End Joining
    David A Boothman; Fiscal Year: 2013
    ..Stable loss of Kub5/Hera expression, either by heterozygote knockout or knockdown by siRNA/shRNA expression, leads to elevated basal DSBs, ATM activation, foci formation ..
  33. The role of deregulated protein synthesis control in Myc-induced tumorigenesis
    Davide Ruggero; Fiscal Year: 2013
    ..We utilized ribosomal protein heterozygote mice as a genetic tool to selectively restore accurate protein synthesis control in E[unreadable]-Myc/+ mice ..
  34. Role of COX-2 in UVB-induced beta-catenin signaling in keratinocytes
    Jill C Pelling; Fiscal Year: 2011
    ..studies using primary mouse and human keratinocytes, as well as in mouse epidermis in vivo using COX-2+/- heterozygote mice and EP2-/- knockout mice and in human skin tumor samples...
  35. Alcohol Induced Chronic Pancreatitis
    Craig D Logsdon; Fiscal Year: 2013
    ..Neither of these mutant trypsin molecules induces pancreatitis or any obvious perturbations when expressed as a heterozygote. However, when R122G or Trypon mice are fed an alcohol diet;they develop profound CP...
  36. The role of glucocerebrosidase in Parkinson's disease
    Roy Alcalay; Fiscal Year: 2013
    ..We have identified 24 heterozygote carriers (22 PD, 2 spouses)...
  37. Exploring The Posterior Pituitary-Bone Connection
    Mone Zaidi; Fiscal Year: 2013
    ..b>Heterozygote mice with circulating OT reduced to half that of wild type mice showed no lactation defect, but instead ..
  38. Genesis and Progression of Cerebral Cavernous Malformations
    Douglas A Marchuk; Fiscal Year: 2012
    ..for lesion genesis, we have created mouse models with targeted mutations of either Ccm1 or Ccm2, where heterozygote animals develop CCM lesions only in a genetic background null for the tumor suppressor Trp53 (p53) gene...
  39. A general Bayesian polymorphism discovery tool
    Gabor Marth; Fiscal Year: 2009
    ..We will develop new algorithms for the difficult problem of INDEL detection;integrate heterozygote detection in diploid traces into our software;enhance sensitivity to detect rare alleles;and include a new ..
  40. Regulation of Spine Morphogenesis by NrCAM
    Patricia F Maness; Fiscal Year: 2013
    ..A double heterozygote analysis will be undertaken to investigate the postulated genetic interaction of NrCAM with Npn-2, PlexA3, and ..
  41. Maternal dietary folic acid and risk of medulloblastoma in a mouse model
    JULIE ANN contact ROSS; Fiscal Year: 2010
    ..Statistical differences between dietary groups in the frequencies of heterozygote offspring and brain tumors that develop over nine months will be determined by chi-square tests...
  42. Brain regions contributing to seizures as a function of age and body temperature
    John C Oakley; Fiscal Year: 2013
    ..1 voltage gated sodium channel and in a newly created cortical and hippocampal GABAergic interneuron specific heterozygote Nav1.1 deleted mouse (IS-mSMEI)...
  43. TLR4 and TGF-beta interactions in HCC induced by HCV and alcohol
    Hidekazu Tsukamoto; Fiscal Year: 2010
    ..Defective TGF-2 signaling in 22 spectrin heterozygote (22sp+/-) mice, leads to aberrant IL-6 and Nanog induction and spontaneous HCC development...
  44. Regulation of BMP signaling in kidney
    Herbert Y Lin; Fiscal Year: 2012
    ..Kidneys of BMP4 null heterozygote mice showed slower growth and branching of ureteric buds (Miyazaki 2000, Hartwig 2005)...
  45. Myogenic Potential of Extraocular Muscle Satellite Cells
    Linda K McLoon; Fiscal Year: 2010
    ..examining 1) the rate of myogenic precursor cell turnover in two mouse DMD models, the mdx and mdx/utrophin+/- heterozygote (mdx/utrhet) mice, and 2) whether inhibition of cell division by gamma irradiation of the EOM prevents sparing ..
  46. The role of GIRK3 in ethanol withdrawal-induced changes in learning and memory
    Megan E Tipps; Fiscal Year: 2012
    ..of the G- protein coupled inwardly rectifying potassium (GIRK) channel family, and GIRK3 knockout (KO) and heterozygote (HET) mice show less severe ethanol withdrawal...
  47. Molecular Etiology of Familial Mediterranean Fever
    Deborah Gumucio; Fiscal Year: 2007
    ..Moreover, the high frequency of mutant pyrin alleles in several human ethnic groups supports a heterozygote (selective) advantage for the mutant allele...
  48. FIBRONECTIN RECEPTOR IN CANDIDA TROPICALIS
    MARGARET HOSTETTER; Fiscal Year: 2003
    ..tropicalis. If either the heterozygote or the homozygous deletion mutant proves to be less virulent than the parent strain, we will analyze the role ..
  49. Phase II, IL-1 Trap for Treatment of Familial Mediterranean Fever
    Steven J Spalding; Fiscal Year: 2010
    ..Subjects will be diagnosed by clinical criteria with at least one heterozygote mutation of the MEFV (pyrin) gene...
  50. METABOLIC HOMEOSTASIS IN LIVER REGENERATION
    LINDA GREENBAUM; Fiscal Year: 1999
    ..target genes which are activated by C/EBPalpha during regeneration will be identified in C/EBPalpha deficient heterozygote mice which we hypothesize will manifest subtle changes in the level of expression of C/EBPalpha regulated genes ..
  51. INBORN ERRORS--MOLECULAR ANALYSIS IN CULTURED CELLS
    Leon Rosenberg; Fiscal Year: 1990
    ..arterial disease; and 5) developing molecular tools which will permit early prenatal diagnosis and reliable heterozygote detection for each of these inborn errors of metabolism...
  52. BPH AND PROSTATE CA IN 5A-REDUCTASE-2 DEFICIENT CARRIERS
    Julianne Imperato McGinley; Fiscal Year: 2000
    ..To test the hypothesis, a unique population of heterozygote males with a known single allelic defect in the 5alpha-reductase-2 gene and a consequent mild decrease in DHT ..
  53. Homocysteine's role in the causation of presbyopia
    CHARLES PRINCE; Fiscal Year: 2002
    ..Specific Aim 1. To recruit at least 30 subjects of each MTHFR genotype (homozygous normal, heterozygote, homozygous mutant), aged 20 to 39 years, and measure their accommodative amplitude in one eye...
  54. BONE MARROW TRANSPLANTATION FOR MUCOPOLYSACCHARIDOSIS
    Chester Whitley; Fiscal Year: 1993
    ..enzymatic activity will be used to confirm the diagnosis of a specific MPS disease, to determine the homozygote/heterozygote genotype of sibling donors, and to follow the course of engraftment...
  55. REPRODUCTIVE EFFECTS OF OXYTOCIN DEFICIENCY
    CHRISTINA LUEDKE; Fiscal Year: 2001
    ..Growth will be evaluated by comparison with wild-type littermates from heterozygote matings. Histologic methods will be used to study organogenesis...
  56. Characterization of N-type Ca channels in growth cones
    Maureen McEnery; Fiscal Year: 2005
    ..The alpha1A ko/ko mouse is ataxic, epileptic, and dystonic; however, the alpha1A heterozygote (ko/+) is asymptomatic...
  57. Chemoprevention of Pituitary Corticotroph Tumors
    Anthony Heaney; Fiscal Year: 2006
    ..This project will examine the chemopreventative actions of CDDO-IM in vivo in the Rb heterozygote knock-out mouse that develops spontaneous pituitary corticotroph tumor...
  58. Mechanisms of regulation of excitability in immature CNS
    Joaquin N Lugo; Fiscal Year: 2010
    ..2 knockout compared with heterozygote and wildtype mice. Aim 2: Investigation of the role of Kv4...
  59. RESPONSE REGULATOR GENE (CASSK1) OF CANDIDA ALBICANS
    Richard Calderone; Fiscal Year: 2004
    ..for virulence of the organism, since knock-out strains in each gene were avirulent in comparison to parental, heterozygote and gene-reconstituted strains...
  60. Adaptation to long chain fatty acid oxidation deficiency
    Arnold Strauss; Fiscal Year: 2007
    ..the 20 bp long VLCAD enhancer we have isolated (Aim 2) and by characterizing VLCAD-deficient mice and their heterozygote littermates that exhibit the phenotypes of sudden death, late-onset obesity, development of tumors, and ..
  61. MOUSE MODEL OF IGA DEFICIENCY USING GENE TARGETING
    Gregory Harriman; Fiscal Year: 1993
    ..b>Heterozygote offspring will be bred to obtain homozygous mice lacking the Igh IgA locus...
  62. Development of Novel Fluorescent Dyes for DNA Sequencing
    MATTHEW MAHINDARATNE; Fiscal Year: 2003
    ..Variation in peak heights is particularly problematic when attempting to quantitate different base mixtures for heterozygote analyses of single nucleotide polymorphisms (SNPs)...
  63. HOMOLOGOUS PREPUBERTAL CANINE GONAD TRANSPLANTATION
    JENNIFER PULLIUM; Fiscal Year: 2007
    ..These high costs and low levels of production are a major hindrance to research when large numbers of heterozygote breeders are required to produce the necessary number of homozygote pups...
  64. The Risk of Cancer in Fanconi Anemia Heterozygotes
    Marianne Berwick; Fiscal Year: 2005
    ..There is evidence that heterozygote carriers of homozygous recessive familial cancer syndromes, such as Fanconi anemia, ataxia telangiectasia and ..