genetic heterogeneity

Summary

Summary: The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)

Top Publications

  1. ncbi Genetic heterogeneity in human disease
    Jon McClellan
    Department of Psychiatry, University of Washington, Seattle, WA 98195 7720, USA
    Cell 141:210-7. 2010
  2. ncbi The causes and consequences of genetic heterogeneity in cancer evolution
    REBECCA A BURRELL
    Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Nature 501:338-45. 2013
  3. ncbi Genetic heterogeneity and cancer drug resistance
    Nicholas C Turner
    Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
    Lancet Oncol 13:e178-85. 2012
  4. 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
  5. ncbi Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp
    Yoshiaki Nagai
    Department of Respiratory Medicine, Saitama Medical School, Moroyama machi, Iruma gun, Saitama, Japan
    Cancer Res 65:7276-82. 2005
  6. pmc Genetic heterogeneity of diffuse large B-cell lymphoma
    Jenny Zhang
    Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 110:1398-403. 2013
  7. pmc How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine
    M Gerlinger
    Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Br J Cancer 103:1139-43. 2010
  8. pmc Tumor heterogeneity: causes and consequences
    Andriy Marusyk
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Biochim Biophys Acta 1805:105-17. 2010
  9. pmc Beyond genome-wide association studies: genetic heterogeneity and individual predisposition to cancer
    Antonella Galvan
    Department of Predictive and for Prevention Medicine, Fondazione IRCCS, Istituto Nazionale Tumori, Via G Venezian 1, 20133 Milan, Italy
    Trends Genet 26:132-41. 2010
  10. ncbi Genetic heterogeneity at the beta-giardin locus among human and animal isolates of Giardiaduodenalis and identification of potentially zoonotic subgenotypes
    Marco Lalle
    Division of Gastroenteric and Tissue Parasitic Diseases, Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161 Rome, Italy
    Int J Parasitol 35:207-13. 2005

Detail Information

Publications287 found, 100 shown here

  1. ncbi Genetic heterogeneity in human disease
    Jon McClellan
    Department of Psychiatry, University of Washington, Seattle, WA 98195 7720, USA
    Cell 141:210-7. 2010
    ..Evolutionary forces generate vast genetic heterogeneity in human illness by introducing many new variants in each generation...
  2. ncbi The causes and consequences of genetic heterogeneity in cancer evolution
    REBECCA A BURRELL
    Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Nature 501:338-45. 2013
    ..A major cause of genetic heterogeneity in cancer is genomic instability...
  3. ncbi Genetic heterogeneity and cancer drug resistance
    Nicholas C Turner
    Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
    Lancet Oncol 13:e178-85. 2012
    ..Although cancers are traditionally thought to be clonal, there is now evidence of intra-tumour genetic heterogeneity in most cancers...
  4. 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...
  5. ncbi Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp
    Yoshiaki Nagai
    Department of Respiratory Medicine, Saitama Medical School, Moroyama machi, Iruma gun, Saitama, Japan
    Cancer Res 65:7276-82. 2005
    ..b>Genetic heterogeneity of EGFR suggests that the EGFR gene is unstable in established cancers and the heterogeneity may explain ..
  6. pmc Genetic heterogeneity of diffuse large B-cell lymphoma
    Jenny Zhang
    Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 110:1398-403. 2013
    ..Thus, our study reveals the tremendous genetic heterogeneity that underlies lymphomas and highlights the need for personalized medicine approaches to treating these ..
  7. pmc How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine
    M Gerlinger
    Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Br J Cancer 103:1139-43. 2010
    ..drugs according to Darwinian models and highlights the roles of genomic instability and high intra-tumour genetic heterogeneity as major accelerators of this evolutionary process...
  8. pmc Tumor heterogeneity: causes and consequences
    Andriy Marusyk
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Biochim Biophys Acta 1805:105-17. 2010
    ..In this perspective, we summarize the sources of intra-tumor phenotypic heterogeneity with emphasis on genetic heterogeneity. We review experimental evidence for the existence of both intra-tumor clonal heterogeneity as well as ..
  9. pmc Beyond genome-wide association studies: genetic heterogeneity and individual predisposition to cancer
    Antonella Galvan
    Department of Predictive and for Prevention Medicine, Fondazione IRCCS, Istituto Nazionale Tumori, Via G Venezian 1, 20133 Milan, Italy
    Trends Genet 26:132-41. 2010
    ..Many of these reasons converge towards the concept of genetic heterogeneity that might implicate hundreds of genetic variants in regulating cancer risk...
  10. ncbi Genetic heterogeneity at the beta-giardin locus among human and animal isolates of Giardiaduodenalis and identification of potentially zoonotic subgenotypes
    Marco Lalle
    Division of Gastroenteric and Tissue Parasitic Diseases, Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161 Rome, Italy
    Int J Parasitol 35:207-13. 2005
    ..Five of these subgenotypes, namely A1, A2, A3, A4 and B3, were found to be associated with infections of humans, of dogs and of calves; these data, therefore, supported the role of these animals as a source of infection for humans...
  11. pmc Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy
    Jens G Lohr
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02412, USA Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA
    Cancer Cell 25:91-101. 2014
    ..These results emphasize the importance of heterogeneity analysis for treatment decisions...
  12. pmc Non-genetic heterogeneity of cells in development: more than just noise
    Sui Huang
    Institute for Biocomplexity and Informatics, Biological Sciences Bldg, Room 539D, University of Calgary, Calgary, AB T3A 0Y1, Canada
    Development 136:3853-62. 2009
    ..of the cell populations that serve as starting material for experimental analysis, attention to such non-genetic heterogeneity has been scant...
  13. ncbi Targeted next-generation sequencing for the molecular genetic diagnostics of cardiomyopathies
    Benjamin Meder
    Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany
    Circ Cardiovasc Genet 4:110-22. 2011
    ..However, because of the genetic heterogeneity and limitations in throughput and scalability of current diagnostic tools up until now, it is hardly ..
  14. ncbi Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases
    Lurdes Torres
    Department of Genetics, Portuguese Oncology Institute, Rua Dr Antonio Bernardino de Almeida, Porto, Portugal
    Breast Cancer Res Treat 102:143-55. 2007
    ..The median intratumor genetic heterogeneity score (HS) was 17...
  15. pmc HomozygosityMapper--an interactive approach to homozygosity mapping
    Dominik Seelow
    Department of Neuropaediatrics, Charite Universitatsmedizin Berlin, Augustenburger Platz 1, D 13353 Berlin, Germany
    Nucleic Acids Res 37:W593-9. 2009
    ..They can at any point restrict access to their data or make it public, allowing HomozygosityMapper to be used as a data repository for homozygosity-mapping studies. HomozygosityMapper is available at http://www.homozygositymapper.org/...
  16. pmc High-throughput sequencing to decipher the genetic heterogeneity of deafness
    Zippora Brownstein
    Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Genome Biol 13:245. 2012
    ..We describe the impact that high-throughput sequencing approaches are having in discovery of genes related to hearing loss and the implications for clinical diagnosis...
  17. pmc We are all individuals: causes and consequences of non-genetic heterogeneity in mammalian cells
    Alexander Loewer
    Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, Berlin Buch, Germany
    Curr Opin Genet Dev 21:753-8. 2011
    ....
  18. pmc IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production
    Lisa M Maier
    Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Genet 5:e1000322. 2009
    ..We demonstrate that multiple variants independently correlate with sIL-2RA levels...
  19. ncbi Breast cancer intratumor genetic heterogeneity: causes and implications
    Charlotte K Y Ng
    Molecular Pathology Team, Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, SW3 6JB, UK
    Expert Rev Anticancer Ther 12:1021-32. 2012
    ..In this review, the evidence of intratumor heterogeneity in breast cancer, its potential causes and implications for the clinical management of breast cancer patients are discussed...
  20. ncbi Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer
    Christoph A Klein
    Institut fur Immunologie, Ludwig Maximilians Universitat Munchen, D 80336 MUnchen, Germany
    Lancet 360:683-9. 2002
    ..Disseminated tumour cells can be detected by epithelial markers in mesenchymal tissues and represent targets for adjuvant therapies...
  21. ncbi Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity?
    Erwin Oechslin
    Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, University Health Network Toronto General Hospital, Toronto, Ontario, Canada
    Eur Heart J 32:1446-56. 2011
    ..Thus, genetic heterogeneity, with an overlap of different phenotypes, and the variability of hereditary patterns, raise the questions ..
  22. ncbi Genetic heterogeneity in the species Leishmania tropica revealed by different PCR-based methods
    G Schonian
    Institut für Mikrobiologie und Hygiene, Charite Campus Mitte, Humboldt Universitat zu Berlin, Dorotheenstr 96, D 10117 Berlin, Germany
    Trans R Soc Trop Med Hyg 95:217-24. 2001
    ..killicki. All techniques revealed a high degree of genetic heterogeneity among the strains of L. tropica...
  23. ncbi Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome
    Laurence Faivre
    Département de Génétique et INSERM U393, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    Am J Med Genet A 123:204-7. 2003
    ..1) was found in one AD WMS family. In order to answer the question of whether or not genetic heterogeneity could be related to a clinical heterogeneity, we reviewed 128 WMS patients from the literature (including ..
  24. pmc Are rare variants responsible for susceptibility to complex diseases?
    J K Pritchard
    Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, United Kingdom
    Am J Hum Genet 69:124-37. 2001
    ..I discuss some practical implications of these results for gene mapping efforts...
  25. pmc Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease
    Jeroen H Roelfsema
    Center for Human and Clinical Genetics, Leiden University Medical Center, Sylvius Laboratory, Leiden, The Netherlands
    Am J Hum Genet 76:572-80. 2005
    ..We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder. These are the first mutations identified in EP300 for a congenital disorder...
  26. pmc Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum
    D Campion
    INSERM EPI 9906, Faculte de Medecine, 76183 Rouen, France
    Am J Hum Genet 65:664-70. 1999
    ..These results show that (1) PSEN1 and APP mutations account for 71% of ADEOAD families and (2) nonpenetrance at age <61 years is probably infrequent for PSEN1 or APP mutations...
  27. pmc Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma
    S L Cooke
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Center, Cambridge, UK
    Oncogene 29:4905-13. 2010
    ..These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment...
  28. ncbi Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines
    Gail H Vance
    Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Arch Pathol Lab Med 133:611-2. 2009
    ..The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%...
  29. pmc Genetic heterogeneity and recombination in canine noroviruses
    Vito Martella
    Department of Veterinary Public Health, University of Bari, Valenzano, Bari, Italy
    J Virol 83:11391-6. 2009
    ..9% nucleotide identity and 98.9% amino acid identity) identified from oysters in Japan, indicating that similar viruses may be common environmental contaminants...
  30. ncbi HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype
    Robert Winchester
    Columbia University, New York, New York 10032, USA
    Arthritis Rheum 64:1134-44. 2012
    ....
  31. pmc Implications of genetic heterogeneity in cancer
    Michael W Schmitt
    Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle, Washington, USA
    Ann N Y Acad Sci 1267:110-6. 2012
    ..The extensive heterogeneity in DNA sequence and continual tumor evolution that would occur in the context of a mutator phenotype have important implications for cancer diagnosis and therapy...
  32. ncbi The inherited ataxias: genetic heterogeneity, mutation databases, and future directions in research and clinical diagnostics
    Joshua Hersheson
    Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom
    Hum Mutat 33:1324-32. 2012
    ..Developing these resources will facilitate a better understanding of the complex genotype-phenotype relationships in these disorders and assist interpretation of gene variants as testing for rarer ataxia genes becomes commonplace...
  33. ncbi Genetic intra-tumour heterogeneity in epithelial ovarian cancer and its implications for molecular diagnosis of tumours
    L Khalique
    Translational Research Laboratory, Department of Gynaecological Oncology, Institute for Women s Health, University College London, UK
    J Pathol 211:286-95. 2007
    ..The basis of genetic ITH and the possible implications for molecular approaches to clinical diagnosis of ovarian cancers may apply to other tumour types...
  34. pmc Genetic heterogeneity of small ruminant lentiviruses involves immunodominant epitope of capsid antigen and affects sensitivity of single-strain-based immunoassay
    Elena Grego
    Dipartimento di Produzioni Animali, Epidemiologia ed Ecologia, Facolta di Medicina Veterinaria, Universita di Torino, 10095 Grugliasco, Italy
    Clin Diagn Lab Immunol 9:828-32. 2002
    ..Additionally, these results support the hypothesis of cross-species transmission based on the phylogenetic analysis described above. This has implications for the control and eradication of small ruminant lentivirus infections...
  35. ncbi Estimation of the frequency of occult mutations for an autosomal recessive disease in the presence of genetic heterogeneity: application to genetic hearing loss disorders
    William J Kimberling
    Center for the Study and Treatment of Usher Syndrome, Boys Town National Research Hospital and the Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68131, USA
    Hum Mutat 26:462-70. 2005
    ..It is especially valuable when the phenotype shows genetic heterogeneity, and its importance will grow as treatments become genotype specific...
  36. pmc Genetic heterogeneity of residual variance - estimation of variance components using double hierarchical generalized linear models
    Lars Rönnegård
    Statistics Unit, Dalarna University, SE 781 70 Borlänge, Sweden
    Genet Sel Evol 42:8. 2010
    ..Here, linear mixed models with genetic effects in the residual variance part of the model can be used. Such models have previously been fitted using EM and MCMC algorithms...
  37. ncbi Clinical and genetic heterogeneity in laminopathies
    Anne T Bertrand
    INSERM, U974, Paris, France
    Biochem Soc Trans 39:1687-92. 2011
    ..Associated with this wide clinical variability, there is also a large genetic heterogeneity, with 408 different mutations being reported to date...
  38. ncbi Familial isolated pituitary adenoma: evidence for genetic heterogeneity
    Rodrigo A Toledo
    Endocrine Genetics Unit LIM 25, Endocrinology, Hospital das Clinicas, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil
    Front Horm Res 38:77-86. 2010
    ..A better knowledge of these susceptibility loci may disclose modifier genes that are likely to play exacerbating or protective roles in the phenotypic diversity of AIP-mutated families...
  39. ncbi Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity
    Karen A Orfali
    Department of Cellular and Molecular Medicine Haematology, St George s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK
    Br J Haematol 125:243-52. 2004
    ..These results have important implications for genetic counselling, and for the selection of potential sibling bone marrow donors...
  40. ncbi Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions
    Frederic G Barr
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 62:4704-10. 2002
    ....
  41. ncbi Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma
    Matija Snuderl
    Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Cancer Cell 20:810-7. 2011
    ..We present an example of genetic heterogeneity in human malignant brain tumors in which multiple closely related driver genes are amplified and activated ..
  42. ncbi Intratumoral heterogeneity of HER2/neu in breast cancer--a rare event
    Wedad Hanna
    Department of Pathology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
    Breast J 13:122-9. 2007
    ....
  43. ncbi Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity
    Marylyn D Ritchie
    Program in Human Genetics and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232 0700, USA
    Genet Epidemiol 24:150-7. 2003
    ..power for some models in the presence of 50% phenocopy, and very limited power in the presence of 50% genetic heterogeneity. Extending MDR to address genetic heterogeneity should be a priority for the continued methodological ..
  44. pmc The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers
    I Aksentijevich
    Section of Genetics, Arthritis and Rheumatism Branch, National Institutes of Health, Bethesda, MD 20892, USA
    Am J Hum Genet 69:301-14. 2001
    ..presented with a compatible clinical history, we have not identified any TNFRSF1A mutation, despite comprehensive genomic sequencing of all of the exons, therefore suggesting further genetic heterogeneity of the periodic-fever syndromes.
  45. ncbi Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation
    A Rodriguez
    Molecular Pathology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    Leukemia 21:1984-91. 2007
    ..There is a molecular heterogeneity in CLL, dependent on the expression of genes defining BCR and MAPK/NF-kappaB clusters, which can be used to predict time to treatment in early clinical stages...
  46. pmc Genetic heterogeneity of hepatitis C virus in association with antiviral therapy determined by ultra-deep sequencing
    Akihiro Nasu
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    PLoS ONE 6:e24907. 2011
    ..Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail.
  47. ncbi XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis
    B Wei
    Department of Urology, Affiliated Wuxi People s Hospital of Nanjing Medical University, Wuxi, China
    Prostate Cancer Prostatic Dis 14:225-31. 2011
    ..However, in subgroup analysis we found a suggestion that XRCC1 399Gln allele might be a low-penetrent risk factor for PCa only in Asian men...
  48. pmc Genetic heterogeneity of self-reported ancestry groups in an admixed Brazilian population
    Tulio C Lins
    Programa de Pós Graduação em Ciências Genômicas e Biotecnologia, Universidade Catolica de Brasilia, DF, Brazil
    J Epidemiol 21:240-5. 2011
    ..The aim of this study was to evaluate the relation of self-reported with genetic ancestry and the statistical risk of grouping an admixed sample based on self-reported ancestry...
  49. ncbi Evidence of genetic heterogeneity for hereditary gingival fibromatosis
    T C Hart
    Division of Oral Biology, University of Pittsburgh School of Dental Medicine, PA 15261, USA
    J Dent Res 79:1758-64. 2000
    ..The apparently different modes of Mendelian inheritance of HGF suggest genetic heterogeneity. A gene locus for HGF has been localized to a 37-cM genetic interval on chromosome 2p21-p22 (D2S1352, Zmax ..
  50. ncbi Assessment of cumulative evidence on genetic associations: interim guidelines
    John P A Ioannidis
    Clinical and Molecular Epidemiology Unit, University of Ioannina School of Medicine, Ioannina 45110, Greece
    Int J Epidemiol 37:120-32. 2008
    ..Future empirical research and consensus development are needed to develop an integrated model for combining epidemiological and biological evidence in the rapidly evolving field of investigation of genetic factors...
  51. pmc Meta-analysis of sex-specific genome-wide association studies
    Reedik Magi
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Genet Epidemiol 34:846-53. 2010
    ....
  52. ncbi EGFR genetic heterogeneity of nonsmall cell lung cancers contributing to acquired gefitinib resistance
    Shi Xu Jiang
    Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan
    Int J Cancer 123:2480-6. 2008
    ..Thus, our results suggest that multiple mechanisms underlie acquired gefitinib resistance, and selection on a background of EGFR genetic heterogeneity also contributes to acquisition of resistance in a proportion of NSCLCs.
  53. ncbi Clinical and genetic heterogeneity in nemaline myopathy--a disease of skeletal muscle thin filaments
    D Sanoudou
    Division of Genetics, Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA
    Trends Mol Med 7:362-8. 2001
    ..These findings are starting to alter the approach that neurologists and geneticists take to diagnosing and counseling patients with NM, and could lead to insights into specific directed therapies in the future...
  54. ncbi Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase
    S H Huang
    Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Boston, Massachusetts, USA
    Nat Genet 11:468-71. 1995
    ..PDEA is the seventh RP gene identified, highlighting the extensive genetic heterogeneity of the disorder and encouraging further investigation into the role of other members of the ..
  55. pmc Confronting complexity in late-onset Alzheimer disease: application of two-stage analysis approach addressing heterogeneity and epistasis
    Tricia A Thornton-Wells
    Biobehavioral Intervention Training Program, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University Institute for Imaging Science, Vanderbilt University, Nashville, Tennessee 37203, USA
    Genet Epidemiol 32:187-203. 2008
    ..Further studies are needed to replicate these statistical findings and to elucidate possible biological interaction mechanisms between LRRTM3 and these genes...
  56. ncbi Clinical and genetic heterogeneity of amyotrophic lateral sclerosis
    M Sabatelli
    Istituto di Neurologia, Universita Cattolica del Sacro Cuore, Rome, Italy
    Clin Genet 83:408-16. 2013
    ..Over the last few years contribution of large- and low-effect genes to sporadic ALS is increasingly recognized...
  57. ncbi Variance component and breeding value estimation for genetic heterogeneity of residual variance in Swedish Holstein dairy cattle
    L Rönnegård
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, PO Box 7023, 750 07 Uppsala, Sweden
    J Dairy Sci 96:2627-36. 2013
    ..The possibility to select for uniformity in Holstein dairy cattle based on these estimates is discussed...
  58. ncbi Dopa-responsive dystonia in British patients: new mutations of the GTP-cyclohydrolase I gene and evidence for genetic heterogeneity
    O Bandmann
    University Department of Clinical Neurology, Institute of Neurology, London, UK
    Hum Mol Genet 5:403-6. 1996
    ..None of these mutations were detected more than once and none of the mutations previously described were found in our patients. No mutations were identified in four families and in two sporadic cases...
  59. pmc Clinical and genetic heterogeneity, overlap with other tumor syndromes, and atypical glucocorticoid hormone secretion in adrenocorticotropin-independent macronodular adrenal hyperplasia compared with other adrenocortical tumors
    Hui Pin Hsiao
    Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Clin Endocrinol Metab 94:2930-7. 2009
    ..We characterized a large series of patients of AIMAH and compared them with patients with other adrenocortical tumors...
  60. pmc Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients
    Sarbashis Das
    School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India
    BMC Genomics 14:404. 2013
    ..Genomic analysis of M. tuberculosis isolates from extra pulmonary patients has not been explored...
  61. pmc High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma
    Edmund A Mroz
    Center for Cancer Research and Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
    Cancer 119:3034-42. 2013
    Although the presence of genetic heterogeneity within the tumors of individual patients is established, it is unclear whether greater heterogeneity predicts a worse outcome...
  62. ncbi Genetic heterogeneity of inflammatory response and skin tumorigenesis in phenotypically selected mouse lines
    Antonella Galvan
    Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
    Cancer Lett 295:54-8. 2010
    ..These findings point to the complex link between skin tumor susceptibility and inflammatory response in mice...
  63. ncbi Genetic heterogeneity by comparative genomic hybridization in BRCAx breast cancers
    Anita Mangia
    Clinical Experimental Oncology Laboratory, National Cancer Institute, Hahneman n 10, 70126, Bari, Italy
    Cancer Genet Cytogenet 182:75-83. 2008
    ..Further studies focusing on specific genes and sequences with more sensitive approaches, such as array-CGH, are warranted to confirm these findings...
  64. ncbi Genetic heterogeneity in uveal melanoma assessed by multiplex ligation-dependent probe amplification
    Justyna Dopierala
    Department of Pathology, School of Cancer Studies, University of Liverpool, Liverpool, UK
    Invest Ophthalmol Vis Sci 51:4898-905. 2010
    To determine intratumor genetic heterogeneity in uveal melanoma (UM) by multiplex ligation-dependent probe amplification (MLPA) in formalin-fixed, paraffin-embedded (FFPE) tumor tissues.
  65. ncbi NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence
    Stefanie Weber
    Inserm U574, Necker Enfants Malades Hospital, Paris 5 University, Paris, France
    Kidney Int 66:571-9. 2004
    ..Mutations of NPHS2 are causative in familial autosomal-recessive (AR) and sporadic steroid-resistant nephrotic syndrome (SRNS). This study aimed to determine the spectrum of NPHS2 mutations and to establish genotype-phenotype correlations...
  66. ncbi Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy
    Anil K Agarwal
    Department of Internal Medicine, Division of Nutrition and Metabolic Diseases and Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Endocrinol Metab 88:4840-7. 2003
    ..We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.
  67. ncbi Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases
    Rohit Mehra
    Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Cancer Res 67:7991-5. 2007
    ..Understanding this molecular heterogeneity is critical to the future development and utility of diagnostic and prognostic PCA biomarkers...
  68. ncbi Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene
    Debora Romeo Bertola
    Department of Pediatrics, Instituto da Criança, HC, University of Sao Paulo, Av Dr Eneas Carvalho de Aguiar, 647, Cerqueira Cesar, 05403 900, Sao Paulo, SP, Brazil
    J Hum Genet 52:521-6. 2007
    ..This description emphasizes that a subset of patients with Costello syndrome could harbor mutations in other genes involved in the RAS-MAPK signaling...
  69. pmc NIPBL mutations and genetic heterogeneity in Cornelia de Lange syndrome
    G Borck
    INSERM U393 and Département de Génétique Médicale, Hopital Necker Enfants Malades, Paris, France
    J Med Genet 41:e128. 2004
  70. ncbi Determining trait locus position from multipoint analysis: accuracy and power of three different statistics
    D A Greenberg
    Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Genet Epidemiol 21:299-314. 2001
    ..For finding linkage to one locus of several contributing to disease expression, assuming the dominant and recessive models with reduced penetrance is a good approximation of the mode of inheritance at that locus...
  71. ncbi A novel DCC mutation and genetic heterogeneity in congenital mirror movements
    C Depienne
    INSERM, UMRS 975, and CNRS 7225 CRICM, Pitie Salpetriere Hospital, Paris, France
    Neurology 76:260-4. 2011
    ..The objective was to study clinical and genetic characteristics of 3 European families with MM and to test whether this disorder is genetically homogeneous...
  72. ncbi Non-genetic heterogeneity and cell fate choice in Dictyostelium discoideum
    Alex Chattwood
    Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
    Dev Growth Differ 53:558-66. 2011
    ..this cell-cell variability does not derive from physical differences in the genetic code it is termed non-genetic heterogeneity. Non-genetic heterogeneity endows cell populations with useful capabilities they could never achieve if ..
  73. ncbi Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity
    Elena Andreucci
    Department of Clinical Pathophysiology, University of Florence, Italy
    Pediatr Nephrol 24:2147-53. 2009
    ..The pathophysiology of SNHL and EVA are still to be defined...
  74. ncbi Genetic heterogeneity in schizophrenia II: conditional analyses of affected schizophrenia sibling pairs provide evidence for an interaction between markers on chromosome 8p and 14q
    Y F Chiu
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA
    Mol Psychiatry 7:658-64. 2002
    ..Thus the analysis of allele sharing at a putative schizophrenia susceptibility locus conditioned on allele sharing at other loci provides another important method for dealing with heterogeneity...
  75. pmc Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300
    Deborah Bartholdi
    J Med Genet 44:327-33. 2007
    ..Recently, it was shown that mutations in EP300, coding for the p300 protein, also cause RSTS. CBP and EP300 are highly homologous genes, which play important roles as global transcriptional coactivators...
  76. ncbi Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl syndrome family cohort
    Haifa Hichri
    Laboratoire de Diagnostic Génétique, Hopitaux Universitaires de Strasbourg, Strasbourg, France
    Eur J Hum Genet 13:607-16. 2005
    ..The significant genetic heterogeneity of this condition is supported by the identification, to date, of eight genes (BBS1-8) implied with cilia ..
  77. ncbi Chromosome 22 array-CGH profiling of breast cancer delimited minimal common regions of genomic imbalances and revealed frequent intra-tumoral genetic heterogeneity
    Magdalena Benetkiewicz
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden
    Int J Oncol 29:935-45. 2006
    ..Our results open up several avenues for continued genetic research of breast cancer...
  78. pmc Mutation analysis in Bardet-Biedl syndrome by DNA pooling and massively parallel resequencing in 105 individuals
    Sabine Janssen
    Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI 48109 5446, USA
    Hum Genet 129:79-90. 2011
    ..Thus, DNA pooling combined with MPR offers a valuable strategy for mutation analysis of large patient cohorts, especially in genetically heterogeneous diseases such as BBS...
  79. pmc New disease gene location and high genetic heterogeneity in idiopathic scoliosis
    Patrick Edery
    Hospices Civils de Lyon, Service de Cytogénétique Constitutionnelle, Bron, France
    Eur J Hum Genet 19:865-9. 2011
    ..In two of these families, our results suggested intra-familial genetic heterogeneity, whereas, in the other, we observed a perfect marker disease co-segregation in two regions at 3q12...
  80. ncbi Genetic heterogeneity among bovine leukemia viruses in Japan and their relationship to leukemogenicity
    Emi Inoue
    Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari Tobetsu, Hokkaido, 061 0293, Japan
    Arch Virol 156:1137-41. 2011
    ..5% of Japanese Black and Holstein cattle, respectively, with EBL. These findings indicate that genetically distinct BLV was associated with EBL in Japan and that the genetic profile may influence the leukemogenicity of the virus...
  81. ncbi Genetic heterogeneity in internal transcribed spacer genes of Balantidium coli (Litostomatea, Ciliophora)
    Francisco Ponce-Gordo
    Departamento de Parasitologia, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramon y Cajal s n, 28040 Madrid, Spain
    Protist 162:774-94. 2011
    ..coli which could be present in the same cell and they are common to the mammal and avian hosts studied. These data do not support B. suis and B. struthionis as distinct species...
  82. ncbi Prevalence and genetic heterogeneity of Borrelia burgdorferi sensu lato in Ixodes ticks in Belgium
    T Kesteman
    Microbiology Department, Université Cathololique de Louvain, Brussels, Belgium
    Acta Clin Belg 65:319-22. 2010
    ..Co-infections were present in 8% of ticks. We emphasize the need for clinical studies to assess the prevalence of specific genospecies-related clinical manifestations of Lyme borreliosis in Belgium...
  83. ncbi Genetic diagnosis of neuroacanthocytosis disorders using exome sequencing
    Ruth H Walker
    Department of Neurology, James J Peters Veterans Affairs Medical Center, Bronx, New York 10468, USA
    Mov Disord 27:539-43. 2012
    Neuroacanthocytoses are neurodegenerative disorders marked by phenotypic and genetic heterogeneity. There are several associated genetic loci, and many defects, including gene deletions and insertions, and missense, nonsense, and ..
  84. ncbi HER2 genetic heterogeneity in breast carcinoma
    Christian Ohlschlegel
    Institute of Pathology, Kantonsspital St Gallen, St Gallen, Switzerland
    J Clin Pathol 64:1112-6. 2011
    To determine the frequency of HER2 genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify ..
  85. pmc Genetic heterogeneity of Myc-induced mammary tumors reflecting diverse phenotypes including metastatic potential
    Eran R Andrechek
    Duke Institute for Genome Sciences and Policy, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 106:16387-92. 2009
    ....
  86. pmc A large-scale mutation search reveals genetic heterogeneity in 3M syndrome
    Celine Huber
    Universite Paris Descartes, AP HP, INSERM, Department of Genetics and INSERM U781, Hopital Necker Enfants Malades, Paris, France
    Eur J Hum Genet 17:395-400. 2009
    ..Lack of mutations in 10/33 cases and exclusion of the CUL7 locus on chromosome 6p21.1 in six consanguineous families strongly support the genetic heterogeneity of the 3M syndrome.
  87. pmc Characterizing heterogeneous cellular responses to perturbations
    Michael D Slack
    Department of Pharmacology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 105:19306-11. 2008
    ....
  88. pmc The genetics of colored sequence synesthesia: suggestive evidence of linkage to 16q and genetic heterogeneity for the condition
    Steffie N Tomson
    Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA
    Behav Brain Res 223:48-52. 2011
    ..Our results implicate a 23 MB region at 16q12.2-23.1, providing the first step in understanding the molecular basis of CSS...
  89. ncbi What can we learn from genetic studies of systemic lupus erythematosus? Implications of genetic heterogeneity among populations in SLE
    H S Lee
    Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
    Lupus 19:1452-9. 2010
    ..that show consistently discrepancy between populations such as PTPN22 and possibly ITGAM, PXK, and LYN (genetic heterogeneity)...
  90. ncbi The breakage-fusion-bridge (BFB) cycle as a mechanism for generating genetic heterogeneity in osteosarcoma
    Shamini Selvarajah
    Department of Pathology and Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada
    Chromosoma 115:459-67. 2006
    ....
  91. pmc Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies
    Matteo Bovolenta
    Department of Experimental and Diagnostic Medicine Section of Medical Genetics, University of Ferrara, Ferrara, Italy
    BMC Med Genet 11:44. 2010
    ....
  92. pmc Genetic heterogeneity of residual variance in broiler chickens
    Suzanne J Rowe
    Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK
    Genet Sel Evol 38:617-35. 2006
    Aims were to estimate the extent of genetic heterogeneity in environmental variance. Data comprised 99 535 records of 35-day body weights from broiler chickens reared in a controlled environment...
  93. ncbi 5-HTTLPR Genotype-Specific Phenotype in Children and Adolescents With Autism
    Camille W Brune
    Institute for Juvenile Research, Department of Psychiatry M C 747, University of Illinois at Chicago, 1747 West Roosevelt Rd, Rm 155, Chicago, IL 60608, USA
    Am J Psychiatry 163:2148-56. 2006
    ..The heterogeneity in these reports may be due to clinical heterogeneity. The authors hypothesized that 5-HTTLPR genotypes would be related to variation in specific symptoms in children with autism...
  94. pmc Genetic heterogeneity and clonal evolution in neuroblastoma
    J Mora
    Departments of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Br J Cancer 85:182-9. 2001
    ..sites during the same surgery or at sequential surgeries without intervening chemotherapy to evaluate genetic heterogeneity. Paired samples from 10 patients (group 2) were used to evaluate clonal selection before and after ..
  95. ncbi Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV)
    C Bruno
    Neuromuscular Disease Unit, Department of Pediatrics, University of Genova, Istituto Giannina Gaslini, Largo G Gaslini 5, I 16147 Genova, Italy
    Neurology 63:1053-8. 2004
    ..The typical presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular form of GSD-IV varies in onset (perinatal, congenital, juvenile, or adult) and severity...
  96. pmc Intra-tumour genetic heterogeneity and poor chemoradiotherapy response in cervical cancer
    S L Cooke
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB20RE, UK
    Br J Cancer 104:361-8. 2011
    Intra-tumour genetic heterogeneity has been reported in both leukaemias and solid tumours and is implicated in the development of drug resistance in CML and AML...
  97. ncbi Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia: clinical and molecular findings in three families supporting genetic heterogeneity in Smith-McCort dysplasia
    Luitgard M Neumann
    Institute of Human Genetics, Charite University Medicine Berlin, Berlin, Germany
    Am J Med Genet A 140:421-6. 2006
    ..No mutation was identified in the SMC family, possibly suggesting genetic heterogeneity of this disorder.
  98. ncbi Genetic heterogeneity and functional properties of intestinal bifidobacteria
    J Mättö
    VTT Biotechnology, Espoo, Finland
    J Appl Microbiol 97:459-70. 2004
    ..several molecular methods for the identification and genotyping of bifidobacteria, and further to investigate genetic heterogeneity and functional properties of bifidobacterial isolates from intestinal samples of Finnish adult subjects.
  99. ncbi MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia
    Mojca Jongen-Lavrencic
    Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
    Blood 111:5078-85. 2008
    ..MicroRNA expression apparently bears specific relationships to the heterogeneous pathobiology of AML. Distinctive microRNA signatures appear of potential value in the clinical diagnosis of AML...
  100. ncbi Familial transthyretin-type amyloid polyneuropathy in Japan: clinical and genetic heterogeneity
    Shu Ichi Ikeda
    Third Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan
    Neurology 58:1001-7. 2002
    ..Less invasive treatments for this disease are required...
  101. pmc Exploring the performance of Multifactor Dimensionality Reduction in large scale SNP studies and in the presence of genetic heterogeneity among epistatic disease models
    Todd L Edwards
    Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tenn, USA
    Hum Hered 67:183-92. 2009
    ..Previously unknown aspects of MDR performance were the power to detect interactive effects given large numbers of non-model loci or varying degrees of heterogeneity among multiple epistatic disease models...

Research Grants78

  1. Identification of Genetic and Epigenetic Alterations in Spondyloarthritis
    Tibor T Glant; Fiscal Year: 2013
    ..However, progress in AS-related genomic research has been hampered by the extreme genetic heterogeneity of the human population, and the fact that human individuals cannot be genetically manipulated...
  2. The Relationship Between STK39, Salt Sensitivity, and HCTZ-induced BP Response
    YEN PEI CHRISTY CHANG; Fiscal Year: 2010
    ..from this work may eventually help to expand our understanding of essential HTN, allowing us to reduce its genetic heterogeneity and convert its management into cost-effective personalized medicine through the identification of ..
  3. Mutational Cloning in Familial Dementia and Alzheimers Disease
    Wendy H Raskind; Fiscal Year: 2010
    ..Second, the genetic heterogeneity of FD of unknown cause will be diminished as families are assigned to subgroups on the basis of mutations ..
  4. Human Stem Cell Model of Niemann Pick Type C
    Lawrence S Goldstein; Fiscal Year: 2010
    ..By conducting parallel analysis of hESC and hIPSC lines we will also address the genetic heterogeneity of NPC, and confirm that pathologic phenotypes found in these cells are specifically due to lack of normal ..
  5. Genome-wide SNP association in psoriasis
    ANNE MARY BOWCOCK; Fiscal Year: 2012
    ..By targeting cases or families with both Ps and PsA we hope to reduce possible genetic heterogeneity. Genes will be prioritized for follow up on the basis of known biological roles/pathway altered in Ps/PsA ..
  6. Mouse models for the functional analysis of asthma-associated human polymorphisms
    Donata Vercelli; Fiscal Year: 2009
    ..with allergic inflammation, but their impact on the phenotype is far from understood because the genetic heterogeneity and complexity existing within outbred populations prevent association studies from revealing which ..
  7. CLONING GENES INVOLVED IN HEARING
    CYNTHIA CASSON MORTON; Fiscal Year: 2012
    ..Unparalleled genetic heterogeneity is a hallmark of genetic deafness, and over 70 genes have been identified largely within the last decade...
  8. Genetic Predisposition To Thoracic Aortic Aneurysms/Dissections
    Dianna M Milewicz; Fiscal Year: 2013
    ..We hypothesize that there are multiple genes responsible for familial TAAD, and this genetic heterogeneity underlies the significant clinical heterogeneity observed in FTAAD...
  9. Combinational Immunotherapy Targeting the Melanoma-Associated Vasculature
    Walter J Storkus; Fiscal Year: 2013
    ..A major reason for disease recurrence and the development of treatment-refractory disease reflects the genetic heterogeneity of tumor cells in a given lesion and the ability of subsets of tumor cells to select for compensatory ..
  10. Non-Viral Gene Therapy for Retinal Degeneration
    Rajendra Kumar-Singh; Fiscal Year: 2013
    ..The high level of genetic heterogeneity observed in retinal degeneration hampers the timely availability of therapies for patients as each gene ..
  11. Genetic Diversity of Sickle Cell Anemia
    Martin H Steinberg; Fiscal Year: 2010
    ..However, finding genetic variation alone is insufficient;as we capture the genetic heterogeneity associated with selected sub-phenotypes of this disease, we will develop predictive network models that ..
  12. Genetic analysis of loci associated with naive airway hyperresponsiveness
    EMILY NONE COZZI; Fiscal Year: 2010
    ..Therefore, murine models with less genetic heterogeneity can be employed...
  13. Mechanistic basis and potential therapies for myosin storage myopathy
    Sanford I Bernstein; Fiscal Year: 2013
    ..of interactions between wild- type and mutant myosin molecules to disease pathology and will obviate genetic heterogeneity that leads to phenotypic variability in the human disease...
  14. Osteosarcoma Genetics Using an Animal Model
    JENNIE L ROWELL; Fiscal Year: 2011
    ..However, further progress is complicated by the high genetic heterogeneity of human populations...
  15. Modifiers of Beta-Amyloid Metabolism and Deposition
    Bruce T Lamb; Fiscal Year: 2013
    ..Due to the inherent variability and genetic heterogeneity in late-onset neurodegenerative disorders, the identification of the remainder of the genetic and ..
  16. Identification of a Novel Gene for Parkinson Disease
    Han Xiang Deng; Fiscal Year: 2012
    ..e. large families with both normal and affected members, especially when great genetic heterogeneity exists...
  17. Gene Dosage Imbalance in Neurodevelopmental Disorders
    David H Ledbetter; Fiscal Year: 2013
    ..Recent evidence has revealed remarkable genetic heterogeneity in these disorders, with a major role for rare, de novo copy number variations (CNVs) or mutations in ..
  18. BIOCHEMISTRY AND MORPHOLOGY OF CONNECTIVE TISSUE
    Jouni Uitto; Fiscal Year: 2013
    ..pathomechanisms of PXE, with emphasis on expansion of the ABCC6 mutation database and exploration of the genetic heterogeneity with respect to vitamin K-dependent genes GGCX and VKORC...
  19. Genotypic Interactions in Brain Cancer Heterogeneity
    Frank B Furnari; Fiscal Year: 2013
    ..By modeling this type of genetic heterogeneity in vivo, we have determined that an IL-6 paracrine mechanism driven by ?EGFR can recruit wtEGFR-expressing ..
  20. Genetic Hotspots for Disease Risk
    MARTIN G contact REESE; Fiscal Year: 2010
    ..This genetic heterogeneity is known to exist for familial diseases, and is anticipated for complex disorders...
  21. IDENTIFICATION OF VUR GENES BY COMBINED LINKAGE ANALYSIS AND EXOME SEQUENCING
    RASHEED ADEBAYO GBADEGESIN; Fiscal Year: 2013
    ..Reasons for this include: variable expression of the disease, difficulty with case ascertainment, genetic heterogeneity and lack of large pedigrees that can facilitate locus identification...
  22. Discovering Human Birth Defect Genes from Chromosomal Rearrangements
    Richard L Maas; Fiscal Year: 2013
    ..Because of phenotypic and genetic heterogeneity, the role of environmental factors, and the rarity of extended pedigrees and well-stratified cohorts, ..
  23. Population genomic analysis of gut microbial colonization in premature infants
    David A Relman; Fiscal Year: 2013
    ..will allow us to track species membership, community structure, metabolic potential, and population-level genetic heterogeneity. We will use these data to test the extent to which initial consortia predict succeeding community ..
  24. VMAT1 in bipolar disorder and schizophrenia
    Falk W Lohoff; Fiscal Year: 2012
    ..e. neuregulin 1), suggest genetic heterogeneity and the existence of additional susceptibility genes in the 8p21 region...
  25. Determining Epigenetic Targets of Milk Thistle Extract in Prostate
    Maureen K Bunger; Fiscal Year: 2010
    ..In the first screen, alleles that show high expression variation in the absence of genetic heterogeneity are determined by examining protein expression in normal human prostate tissue from unrelated individuals ..
  26. Genetic Susceptibility of Estrogen Induced Mammary Cancer
    James D Shull; Fiscal Year: 2012
    ..Development of each congenic strain will be directed by preliminary data that are indicative of genetic heterogeneity across Emca8...
  27. ADPKD: Disease Spectrum &Genotype-Phenotype Correlations
    Peter C Harris; Fiscal Year: 2013
    ..including potential miRNA binding sites;cryptic splicing;mosaicism;gene conversion to PKD1;and further genetic heterogeneity. A group of ~170 families without detected conventional PKD1 or PKD2 mutations will be available, as well ..
  28. Immunogenetic Studies in Multiple Sclerosis
    Jorge R Oksenberg; Fiscal Year: 2013
    ..Based on the hypothesis that genetic heterogeneity is inherent to MS, and the understanding that patterns of genomic disequilibrium are shaped by the history ..
  29. Shared Genomic Segments in Multiplex Families with Gastroschisis
    MARCIA LYNN FELDKAMP; Fiscal Year: 2013
    ..of these 30 high-risk families may have a different gene(s) that confers gastroschisis susceptibility (genetic heterogeneity). At each locus, the responsible allele(s) may vary between families (allelic heterogeneity)...
  30. AIDS INTERNATIONAL TRAINING AND RESEARCH PROGRAM
    Lee H Harrison; Fiscal Year: 2013
    ..In India, ongoing projects include studies of genetic heterogeneity of Indian HIV strains, CDS suppression of HIV, HIV incidence studies to identify high- risk populations, ..
  31. NOVEL GLOBIN GENE MODULATORS
    SUSAN PARK PERRINE; Fiscal Year: 2013
    ..A challenge to successful application of HbF inducers in the beta-thalassemias has been the genetic heterogeneity, which produces variable baseline fetal globin levels (and as yet unpredictable) responsiveness to HbF-..
  32. A comprehensive approach to breast cancer susceptibility across the risk spectrum
    SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2013
    ..to research questions in genetic susceptibility, for which linkage analysis is confounded by extensive genetic heterogeneity and candidate gene studies technologically limited to small numbers of genes...
  33. Mouse models of human cerebellar malformations
    KATHLEEN JOYCE MILLEN; Fiscal Year: 2010
    ..of this clinically important birth defect remain largely undefined, there is evidence for considerable genetic heterogeneity and complex inheritance...
  34. Localization of nonsyndromic hearing impairment genes
    SUZANNE MARGARET LEAL; Fiscal Year: 2013
    ..However, the vast majority of NSHI genes have neither been localized nor identified. The extreme genetic heterogeneity of NSHI is due to the different processes which can malfunction within the inner ear and cause the hearing ..
  35. DICER1 and the Pleuropulmonary Blastoma Family Cancer Syndrome
    Dana Ashley Hill; Fiscal Year: 2013
    ..These experiments will shed light on the genetic heterogeneity of PPB and will allow us to measure the penetrance and expressivity of DICER1 mutations...
  36. Molecular Targets in T Lineage Leukemia
    Monique Dail; Fiscal Year: 2012
    ..I have generated a cohort of 70 primary transplantable T-ALLs that display remarkable biochemical and genetic heterogeneity thereby recapitulating the diversity observed in human cancer...
  37. The germline variation in immune and epigenetic pathways and melanoma prognosis
    Tomas Kirchhoff; Fiscal Year: 2013
    ..The selection of AJ ancestry will significantly improve the design by reducing the genetic heterogeneity and enhancing the analytical power by identification of founder alleles associated with survival, that are ..
  38. Genetic Determinants of Uterine Fibroids in African-American and Caucasian Women
    Brahim Aissani; Fiscal Year: 2013
    ..of ULs in susceptible individuals: 1) the absence of FH genotype-phenotype correlations, 2) the marked genetic heterogeneity in ULs, and 3) the failure to observe ULs or multiple leiomyomatosis in siblings or parents of cases with ..
  39. A Novel single-tier Lyme disease assay using Borrelia burgdorferi Protein Arrays.
    Benjamin J Luft; Fiscal Year: 2012
    ..However, serodiagnosis of the disease is particularly difficult due to the high level of genetic heterogeneity of B. burgdorferi isolates, even among those collected from a single location...
  40. Growth Control in Multiple Myeloma
    Bart Barlogie; Fiscal Year: 2013
    ..clinical scientists is aimed at further overcoming the tremendous obstacles posed by MM's extensive genetic heterogeneity. We hypothesize that MM subjugates various ME components, perhaps in a MM subtypespecific manner, and that ..
  41. Referral Center-Animal models of human genetic disease
    Mark E Haskins; Fiscal Year: 2013
    ..of such diseases is present in existing dog and cat breeds that are relatively inbred but that retain genetic heterogeneity similar to that present in the Old Order Amish and Ashkenazi Jewish populations...
  42. High-Throughput Single-Cell-PCR Technique for Tissue Analysis of Genetic Heteroge
    Emil P Kartalov; Fiscal Year: 2013
    ..by applicant): We propose a novel single-cell high-sensitivity high-throughput technique for analysis of genetic heterogeneity across tissue samples...
  43. Pancreas cancer combination therapy based on stromal modulators and nano-carriers
    Robert M Straubinger; Fiscal Year: 2013
    ..A number of factors contribute to the challenges in the treatment. One is the disease's genetic heterogeneity such that "one size fit all" approach to treatment development has yielded limited progress and ..
  44. Identification of Autosomal Recessive Nonsyndromic Hearing Impairment Genes
    SUZANNE MARGARET LEAL; Fiscal Year: 2013
    ..However, the vast majority of NSHI genes have neither been localized nor identified. The extreme genetic heterogeneity of NSHI is due to the different processes which can malfunction within the inner ear and cause the hearing ..
  45. An adenoviral/piggyBac hybrid system to accelerate cancer gene validation(PQ #9)
    Adam J Dupuy; Fiscal Year: 2013
    ..With this degree of genetic heterogeneity, distinguishing rare driver mutations from the more abundant passenger events is a daunting task...
  46. Novel prostate cancer oncogenes identified by transposon mutagenesis
    Paul C Marker; Fiscal Year: 2013
    ..The primary screen utilized transposon-based insertional mutagenesis in mice to model genetic heterogeneity in prostate cancer and conduct a genome-wide screen for new oncogenes and tumor suppressor genes...
  47. Massively Parallel Sequencing for Familial Colon Cancer Genes
    SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2013
    ..to research questions in genetic susceptibility for which linkage analysis is confounded by extensive genetic heterogeneity. Taking advantage of unparalleled familial cancer genetics resources available through the Utah Population ..
  48. A Novel Essential Gene for Human Cognitive Function
    MICHAEL EDWARD COULTER; Fiscal Year: 2013
    ..ID and ASD are highly heritable, but because of genetic heterogeneity only about 15% of ASD patients and 50% of ID patients have a specific genetic diagnosis...
  49. Organismal and Genetic Networks in Drug Reward and Reinforcement
    Lisa M Tarantino; Fiscal Year: 2013
    ..human populations have met with some success but are complicated by lack of environmental control, genetic heterogeneity, the need for large sample sizes and ethical concerns...
  50. PROXIMAL DETERMINANTS OF NEPHRITOGENIC AUTOIMMUNITY
    Mary H Foster; Fiscal Year: 2012
    ..Collectively, these strains model the genetic heterogeneity of human lupus, and their study should ultimately provide insight into regulatory and disease mechanisms ..
  51. Role of polycystin-1 in centrosome duplication and cell cycle control
    GABRIELE LUCA GUSELLA; Fiscal Year: 2010
    To date, the molecular mechanisms responsible for the remarkable genetic heterogeneity found in ADPKD cysts remain unknown. Similar karyotypic alterations have been described consequently to genomic instability...
  52. Modeling heterogeneity for safe cancer prevention and detection
    David W Threadgill; Fiscal Year: 2013
    ..new mouse population called the Collaborative Cross that accurately models both germline and somatic genetic heterogeneity present within patient populations...
  53. Identification of a naturally occurring model for EBV-associated lymphomagenesis
    Nicola J Mason; Fiscal Year: 2013
    ..The limited genetic heterogeneity within the breed provides a unique opportunity to identify viral factors and genes that predispose to ..
  54. Alzheimer's Disease Genetics Consortium
    GERARD DAVID SCHELLENBERG; Fiscal Year: 2013
    ..The sample needed to detect a given effect size depends on genetic heterogeneity, which is difficult to predict for AD...
  55. Evaluation of NF1 as a Major Breast Cancer Driver
    John C Schimenti; Fiscal Year: 2013
    ..This approach is complicated by the genetic heterogeneity of patients and variety of tumor types...
  56. EPIDEMIOLOGY OF PBC: A GENOME-WIDE ASSOCIATION STUDY
    MERRILL E GERSHWIN; Fiscal Year: 2011
    ..The use of our Italian population will minimize genetic heterogeneity and every case of PBC will be verified using international criteria...
  57. Malaria Transmission and the Impact of Control Efforts in Southern Africa
    Peter C Agre; Fiscal Year: 2013
    ..Population genetic studies of the vector and parasite will allow characterization of the genetic heterogeneity associated with natural and imposed bottle necks and the changing frequency of insecticide resistance and ..
  58. ENHANCEMENT OF THE CPRC-SPF RHESUS MONKEY PROGRAM
    Carlos A Sariol; Fiscal Year: 2013
    ..U24 SPF and SPF-A colonies and to optimize the structure of breeding groups, maximizing the level of their genetic heterogeneity. At the end of this four year grant, the SPF-A colony will be closed...
  59. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    Sophia Y Cleland; Fiscal Year: 2010
    ..Because significant genetic heterogeneity in disease alleles has been shown to exist among ethnic groups, this study hypothesizes that cytokine ..
  60. Signal processing for accurate detection of copy number variants in cancer
    Rebecca A Betensky; Fiscal Year: 2013
    ..Copy number variations (CNVs) represent a significant part of human genetic heterogeneity and have also been associated with a wide range of diseases and disorders...
  61. Dissection of HDL function using mouse models
    Aldons Jake Lusis; Fiscal Year: 2013
    ..Studies of HDL function in humans are complicated by genetic heterogeneity and environmental factors...
  62. DEVELOPING A NORTH AMERICAN MITOCHONDRIAL DISEASE CONSORTIUM (NAMDC)
    Russell P Saneto; Fiscal Year: 2010
    ..Together with their rarity, the clinical and genetic heterogeneity of mitochondrial diseases has hindered natural history studies and rigorous clinical trials...
  63. NEW AMINO ACID DISORDERS IN CEREBRAL DISEASE
    Vivian Shih; Fiscal Year: 1999
    ..In homocystinuria (HCS) due to cystathionine beta-synthase deficiency, DNA mutations and genetic heterogeneity will be investigated in patients with both the B6 responsive and nonresponsive forms and in those from ..
  64. Tracking Cancer Stem Cell Evolution
    John Welsh; Fiscal Year: 2009
    ..We propose to track the evolution of intratumoral genetic heterogeneity in single tumors, and use this data to model tumor development by means of oncogenetic trees...
  65. CLEFT LIP AND PALATE IN LOS ANGELES HISPANICS
    M Spence; Fiscal Year: 1990
    ..Given this new evidence for genetic heterogeneity and the fact that our sample from RLAH is twice the size we predicted, our renewal focuses on the genetic ..
  66. GENETIC HETEROGENEITY IN HUMAN DISEASE
    Aravinda Chakravarti; Fiscal Year: 1992
    ..By analyzing beta-globin, PKU, cystic fibrosis and LDL-receptor gene mutations and linked DNA polymorphisms we wish to delineate allelic heterogeneity and determine probable mechanisms of origin and maintenance of specific mutations...
  67. GENETIC LINKAGE BETWEEN UC AND THE HLA CLASS II LOCI
    Richard Duerr; Fiscal Year: 1999
    ..for UC susceptibility genes is complicated by complex genetics, including incomplete penetrance, probable genetic heterogeneity, and probable multilocus inheritance...
  68. Determinants of HbF Response to Hydroxyurea
    Martin Steinberg; Fiscal Year: 2005
    ..To define this genetic heterogeneity, we will use high throughput screening by mass spectrometry to: discover single nucleotide polymorphisms (..
  69. GENETIC EPIDEMIOLOGY OF ESSENTIAL TREMOR
    Elan Louis; Fiscal Year: 1999
    ..on whether the degree of familial aggregation of ET is greater for certain subtypes of ET than for others (genetic heterogeneity)...
  70. Genetic Heterogeneity and Protein Function in DBA
    Colin Sieff; Fiscal Year: 2003
    ..and other pedigrees do not show evidence for linkage to either chromosome 8p or 19q, indicating further genetic heterogeneity. The long term objective of this proposal is to identify and isolate the DBA2 gene...
  71. X-LINKED CHARCOT-MARIE TOOTH DISEASE
    Thaddeus Kelly; Fiscal Year: 1990
    ..a phenotype which is then investigated for familial aggregation and pattern of inheritance; evidence for genetic heterogeneity is sought. Markers and protein studies attempt to move closer to the gene product...
  72. GENETIC CONTROL OF NEUROMUSCULAR DEGENERATION IN MICE
    Gregory Cox; Fiscal Year: 2002
    ..The vast genetic heterogeneity observed in familial cases of ALS and the high proportion of sporadic cases (approximately 90% of patients)..
  73. Mutational Analysis of Peroxisome Biogenesis Disorders
    Joseph Hacia; Fiscal Year: 2006
    ..biogenesis disorders (PBDs) are inborn errors of metabolism with considerable clinical, biochemical, and genetic heterogeneity. The rational design of effective treatments for these disorders requires the precise identification of ..
  74. PULMONARY HYPERTENSION--MECHANISMS AND FAMILY REGISTRY
    James Loyd; Fiscal Year: 2003
    ..marker studies in six families have identified linkage to chromosome 2q31 without evidence of genetic heterogeneity. The current application will expand the Registry in order to obtain enough PPH families to localize and ..
  75. GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY
    Virginia Kimonis; Fiscal Year: 2003
    ..In addition to clinical heterogeneity within the LGMD category, genetic heterogeneity is indicated by the existence of dominant and recessive forms...
  76. GENETIC HETEROGENEITY IN HOMOCYSTEINE REMETHYLATION
    Barry Shane; Fiscal Year: 2000
    ..The long term goals of the project are to delineate the role of genetic heterogeneity in the development of hyperhomocysteinemia and to understand the mechanisms by which homocysteine ..
  77. The role of selection and genetic diversity in cancer progression
    LAUREN MERLO; Fiscal Year: 2009
    ..our objectives are to develop new cell culture models for measuring fitness, and to examine the role of genetic heterogeneity in neoplastic progression and therapeutic resistance...
  78. Molecular Analysis in Classical Ehlers-Danlos Syndrome
    Anna Mitchell; Fiscal Year: 2009
    ..It exhibits genetic heterogeneity, with alterations in the COL5A1, COL5A2 (components of type V collagen), COL1A1, COL1A2 (components of ..