penetrance

Summary

Summary: The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)

Top Publications

  1. pmc Variability in gene expression underlies incomplete penetrance
    Arjun Raj
    Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 463:913-8. 2010
  2. pmc Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study
    Daniel G Healy
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Lancet Neurol 7:583-90. 2008
  3. pmc Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium
    Annegien Broeks
    Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Hum Mol Genet 20:3289-303. 2011
  4. ncbi Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases
    Irene Catucci
    IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
    Hum Mutat 31:E1052-7. 2010
  5. pmc Meta-analysis of BRCA1 and BRCA2 penetrance
    Sining Chen
    Departments of Environmental Health Sciences and Biostatistics, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    J Clin Oncol 25:1329-33. 2007
  6. ncbi Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10
    Karin Frank-Raue
    Endocrine Practice and Molecular Laboratory, Heidelberg, Germany
    Hum Mutat 32:51-8. 2011
  7. pmc Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Am J Hum Genet 91:97-108. 2012
  8. pmc Systematic search for enhancer elements and somatic allelic imbalance at seven low-penetrance colorectal cancer predisposition loci
    Iina Niittymäki
    Department of Medical Genetics, Genome Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    BMC Med Genet 12:23. 2011
  9. pmc Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression
    Alireza Baradaran-Heravi
    Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Hum Mol Genet 21:2572-87. 2012
  10. ncbi A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population
    Aiko Sueta
    Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1 1, Kanokoden, Chikusa ku, Nagoya 464 8681, Japan
    Breast Cancer Res Treat 132:711-21. 2012

Research Grants

Detail Information

Publications323 found, 100 shown here

  1. pmc Variability in gene expression underlies incomplete penetrance
    Arjun Raj
    Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 463:913-8. 2010
    ..Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation...
  2. pmc Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study
    Daniel G Healy
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Lancet Neurol 7:583-90. 2008
    ..LRRK2-associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2?..
  3. pmc Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium
    Annegien Broeks
    Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Hum Mol Genet 20:3289-303. 2011
    ..This may eventually result in further improvements in prevention, early detection and treatment...
  4. ncbi Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases
    Irene Catucci
    IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
    Hum Mutat 31:E1052-7. 2010
    ..None of the performed analyses showed statistically significant results. In conclusion, our data suggested lack of association between SNPs rs2910164, rs11614913 and rs3746444 and breast cancer risk, or age at breast cancer onset...
  5. pmc Meta-analysis of BRCA1 and BRCA2 penetrance
    Sining Chen
    Departments of Environmental Health Sciences and Biostatistics, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    J Clin Oncol 25:1329-33. 2007
    ..Risk prediction provided by the counselor requires reliable estimates of the mutation penetrance. Such penetrance has been investigated by studies worldwide. The reported estimates vary...
  6. ncbi Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10
    Karin Frank-Raue
    Endocrine Practice and Molecular Laboratory, Heidelberg, Germany
    Hum Mutat 32:51-8. 2011
    ..Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were ..
  7. pmc Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Am J Hum Genet 91:97-108. 2012
    ..performed exome sequencing on 572 ClinSeq participants, and in 37 genes, we interpreted variants that cause high-penetrance cancer syndromes by using an algorithm that filtered results on the basis of mutation type, quality, and ..
  8. pmc Systematic search for enhancer elements and somatic allelic imbalance at seven low-penetrance colorectal cancer predisposition loci
    Iina Niittymäki
    Department of Medical Genetics, Genome Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    BMC Med Genet 12:23. 2011
    ..In this study, we aimed to gain insight into the molecular basis of seven low-penetrance CRC loci tagged by rs4779584 at 15q13, rs10795668 at 10p14, rs3802842 at 11q23, rs4444235 at 14q22, rs9929218 at ..
  9. pmc Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression
    Alireza Baradaran-Heravi
    Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Hum Mol Genet 21:2572-87. 2012
    ..We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.
  10. ncbi A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population
    Aiko Sueta
    Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1 1, Kanokoden, Chikusa ku, Nagoya 464 8681, Japan
    Breast Cancer Res Treat 132:711-21. 2012
    ..Risk models which include a genetic risk score are possibly useful in distinguishing women at high risk of breast cancer from those at low risk, particularly in the context of targeted prevention...
  11. pmc TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers
    N Finch
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neurology 76:467-74. 2011
    ....
  12. ncbi A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length
    D R Langbehn
    Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA, USA
    Clin Genet 65:267-77. 2004
    ..This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.
  13. pmc Exome sequencing identifies a missense mutation in Isl1 associated with low penetrance otitis media in dearisch mice
    Jennifer M Hilton
    Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
    Genome Biol 12:R90. 2011
    ..Genetic studies suggest an inherited component, but few of the genes that contribute to this condition are known. Mouse mutants have contributed significantly to the identification of genes predisposing to otitis media..
  14. pmc Gene-environment interactions in Leber hereditary optic neuropathy
    Matthew Anthony Kirkman
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, UK
    Brain 132:2317-26. 2009
    ..Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to confirm this to be the case...
  15. ncbi Isoleucyl-tRNA synthetase levels modulate the penetrance of a homoplasmic m.4277T>C mitochondrial tRNA(Ile) mutation causing hypertrophic cardiomyopathy
    Elena Perli
    Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Roma, Italy
    Hum Mol Genet 21:85-100. 2012
    The genetic and epigenetic factors underlying the variable penetrance of homoplasmic mitochondrial DNA mutations are poorly understood. We investigated a 16-year-old patient with hypertrophic cardiomyopathy harboring a homoplasmic m...
  16. pmc CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance
    Giulia Venturini
    Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
    PLoS Genet 8:e1003040. 2012
    ..In some cases, such mutations display incomplete penetrance, implying that certain carriers develop retinal degeneration while others have no symptoms at all...
  17. pmc A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function
    Lubka T Roumenina
    Cordeliers Research Center, INSERM Unité Mixte de Recherche en Santé, Paris, France
    Blood 119:4182-91. 2012
    ..These genetic background differences could explain the R139W-aHUS incomplete penetrance. These results demonstrate that this C3 mutation, especially when associated with an at-risk FH and/or MCP ..
  18. ncbi Factors influencing disease phenotype and penetrance in HFE haemochromatosis
    J Rochette
    Universite de Picardie Jules Verne, UFR de Medecine, INSERM UMR, Amiens, France
    Hum Genet 128:233-48. 2010
    ..We discuss penetrance, explaining that this concept normally does not apply to autosomal recessive disorders, and discuss the ..
  19. pmc Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype
    Elena Bresin
    Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Ranica, Bergamo, Italy
    J Am Soc Nephrol 24:475-86. 2013
    ..in complement genes reportedly contribute to atypical hemolytic uremic syndrome (aHUS), but incomplete penetrance suggests that additional factors are necessary for the disease to manifest...
  20. ncbi Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutation
    Ioana N Milos
    Section of Preventive Medicine, Department of Nephrology, University of Freiburg Medical Centre, Freiburg im Breisgau, Germany
    Endocr Relat Cancer 15:1035-41. 2008
    ..By international efforts, we ascertained all available carriers of the RET C634W mutation. Age at diagnosis, penetrance, and clinical complications were analyzed for medullary thyroid carcinoma (MTC), pheochromocytoma, and ..
  21. pmc Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background
    Gavin Hudson
    Mitochondrial Research Group, Department of Ophthalmology and Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Am J Hum Genet 81:228-33. 2007
    ..LHON) is due primarily to one of three common point mutations of mitochondrial DNA (mtDNA), but the incomplete penetrance implicates additional genetic or environmental factors in the pathophysiology of the disorder...
  22. ncbi Novel A14841G mutation is associated with high penetrance of LHON/C4171A family
    Juhua Yang
    Biomedical Engineering Center, Fujian Medical University, Fuzhou, Fujian, China
    Biochem Biophys Res Commun 386:693-6. 2009
    ..This family has high penetrance of visual impairment and extremely low frequency of vision recovery, which is in marked contrast to previously ..
  23. ncbi Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes
    Mika Asai-Coakwell
    Department of Ophthalmology, University of Alberta, Edmonton, Canada
    Hum Mol Genet 18:1110-21. 2009
    ..evident between patients and animal models included pleiotropic effects, variable expressivity and incomplete penetrance. These data establish the important role of this determinant in ocular and vertebral development, demonstrate ..
  24. ncbi The variable expressivity and incomplete penetrance of the twist-null heterozygous mouse phenotype resemble those of human Saethre-Chotzen syndrome
    P Bourgeois
    Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS INSERM U184, Institut de Chimie Biologique, Strasbourg Cedex, France
    Hum Mol Genet 7:945-57. 1998
    ..The twist -null mutant mouse model, combined with other mutant mouse strains, might also help in an understanding of the etiology of morphological abnormalities that appear in human patients affected by other syndromes...
  25. ncbi Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland
    Anu Puomila
    Department of Medical Genetics, University of Turku, Turku, Finland
    Eur J Hum Genet 15:1079-89. 2007
    We have performed an entire-population-based survey of the epidemiology and penetrance of Leber hereditary optic neuropathy (LHON) in Finland - a country that is among the best-studied genetic isolates in the world...
  26. ncbi Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles
    Sheila Seal
    Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Nat Genet 38:1239-41. 2006
    ..Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers...
  27. ncbi High penetrance of pheochromocytoma associated with the novel C634Y/Y791F double germline mutation in the RET protooncogene
    Rodrigo A Toledo
    Faculdade de Medicina da Universidade de Sao Paulo, Avenida Dr Arnaldo, 455, 5 degrees andar, Cerqueira Cesar, 012406 903, Sao Paulo, Brazil
    J Clin Endocrinol Metab 95:1318-27. 2010
    ..Previous studies have shown that double RET mutations may be associated with unusual multiple endocrine neoplasia type 2 (MEN 2) phenotypes...
  28. ncbi A mechanism for gene-environment interaction in the etiology of congenital scoliosis
    Duncan B Sparrow
    Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia
    Cell 149:295-306. 2012
    ..genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects...
  29. pmc Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity
    C Vaisse
    Centre National de la Recherche Scientifique, UPRES A 8090, Institute of Biology of Lille, Lille, France
    J Clin Invest 106:253-62. 2000
    ..Taken together, these results demonstrate that MC4-R mutations are a frequent but heterogeneous genetic cause of morbid obesity...
  30. ncbi Genotype/phenotype and penetrance studies in melanoma families with germline CDKN2A mutations
    J A Bishop
    ICRF Genetic Epidemiology Laboratory, Leeds, UK
    J Invest Dermatol 114:28-33. 2000
    ..Until formal gene testing is available, all members of families with an excessive number of melanoma cases should be treated as potential mutation carriers at increased risk of melanoma...
  31. ncbi Haploinsufficiency in mouse models of DNA repair deficiency: modifiers of penetrance
    Diane C Cabelof
    Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48201, USA
    Cell Mol Life Sci 69:727-40. 2012
    ..In light of a better understanding that the role of DNA repair haploinsufficiency may play in penetrance of other oncogenic or disease causing factors, it may be in the interest of human health and disease prevention ..
  32. ncbi Incomplete penetrance and variable expressivity: is there a microRNA connection?
    Jasmine K Ahluwalia
    Dr B R Ambedkar Centre for Biomedical Research, Delhi University, Delhi, India
    Bioessays 31:981-92. 2009
    Incomplete penetrance and variable expressivity are non-Mendelian phenomena resulting in the lack of correlation between genotype and phenotype...
  33. pmc Quantile-specific penetrance of genes affecting lipoproteins, adiposity and height
    Paul T Williams
    Lawrence Berkeley National Laboratory, Berkeley, California, United States of America
    PLoS ONE 7:e28764. 2012
    Quantile-dependent penetrance is proposed to occur when the phenotypic expression of a SNP depends upon the population percentile of the phenotype...
  34. ncbi Modelling the effects of penetrance and family size on rates of sporadic and familial disease
    Ammar Al-Chalabi
    Department of Clinical Neuroscience, Medical Research Council Centre for Neurodegeneration Research, London, UK
    Hum Hered 71:281-8. 2011
    ..We therefore explored the role of two key parameters that influence ascertainment, penetrance and family size, in rates of observed familiality.
  35. ncbi Cardiac myosin binding protein-C mutations in families with hypertrophic cardiomyopathy: disease expression in relation to age, gender, and long term outcome
    Stephen P Page
    Inherited Cardiovascular Disease Unit, The Heart Hospital, London, United Kingdom
    Circ Cardiovasc Genet 5:156-66. 2012
    ..The aim of this study was to test this hypothesis in a large series of families with HCM associated with MYBPC3 mutations...
  36. ncbi Polygenes, risk prediction, and targeted prevention of breast cancer
    Paul D P Pharoah
    Department of Oncology, University of Cambridge, United Kingdom
    N Engl J Med 358:2796-803. 2008
    ..New developments in the search for susceptibility alleles in complex disorders provide support for the possibility of a polygenic approach to the prevention and treatment of common diseases...
  37. ncbi Pheochromocytoma penetrance varies by RET mutation in MEN 2A
    Frank J Quayle
    Washington University School of Medicine, St Louis, MO 63110, USA
    Surgery 142:800-5; discussion 805.e1. 2007
    ..The occurrence of pheochromocytoma in multiple endocrine neoplasia type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC expression for specific MEN 2A RET mutations...
  38. pmc Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice
    Harini Sampath
    Center for Research on Occupational and Environmental Toxicology, Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, USA
    Am J Physiol Endocrinol Metab 300:E724-34. 2011
    ..Collectively, these data indicate that NEIL1 deficiency results in an increased susceptibility to obesity and related complications potentially by lowering the threshold for tolerance of cellular oxidative stress in neil1(-/-) mice...
  39. ncbi Phenotypic characterization of Bbs4 null mice reveals age-dependent penetrance and variable expressivity
    Erica R Eichers
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza Room 604B, Houston, TX 77030, USA
    Hum Genet 120:211-26. 2006
    ..Evaluations of these null mice have uncovered phenotypic features with age-dependent penetrance and variable expressivity, partially recapitulating the human BBS phenotype.
  40. ncbi M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance
    Agnieszka Pollak
    Institute of Physiology and Pathology of Hearing, Warsaw, Poland
    Am J Med Genet A 143:2534-43. 2007
    ..was to test a hypothesis that M34T and V37I are pathogenic but have distinct features resulting in a reduced penetrance. We screened for known GJB2/GJB6 mutations 233 Polish consecutive unrelated subjects with non-syndromic, ..
  41. ncbi Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force
    Evelyn P Whitlock
    Oregon Evidence Based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon 97227 1110, USA
    Ann Intern Med 145:209-23. 2006
    ..The U.S. Preventive Services Task Force (USPSTF) has not previously considered screening for hereditary hemochromatosis for a recommendation as a clinical preventive service for primary care clinicians...
  42. ncbi Epistatic interactions with a common hypomorphic RET allele in syndromic Hirschsprung disease
    L De Pontual
    université Paris René Descartes, Faculte de Medecine, INSERM U 781, AP HP, Hopital Necker Enfant Malades, Paris, France
    Hum Mutat 28:790-6. 2007
    ..According to the HSCR syndrome, the penetrance of HSCR trait varies from 5 to 70%. Trisomy 21 (T21) also predisposes to HSCR...
  43. ncbi Low penetrance breast cancer predisposition SNPs are site specific
    Niall Mcinerney
    Department of Surgery, Clinical Science Institute, University College Hospital, Galway, Ireland
    Breast Cancer Res Treat 117:151-9. 2009
    Large scale association studies have identified low penetrance susceptibility alleles that predispose to breast cancer. A locus on chromosome 8q24...
  44. ncbi High-penetrance mouse model of acute promyelocytic leukemia with very low levels of PML-RARalpha expression
    Peter Westervelt
    Washington University, Division of Oncology, 660 S Euclid Ave, Campus Box 8007, St Louis, MO 63110 1093, USA
    Blood 102:1857-65. 2003
    ..in the cathepsin G locus and that a knock-in model might yield much higher expression levels and higher penetrance of disease...
  45. 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
    ..and R92Q among patients with periodic fever, as well as functional studies of TNFRSF1A, argue that these are low-penetrance mutations rather than benign polymorphisms. The c...
  46. ncbi Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice heterozygous for the gene encoding the nucleolar protein Treacle
    Jill Dixon
    School of Biological Sciences and Department of Dental Medicine and Surgery, University of Manchester, Manchester, United Kingdom
    Dev Dyn 229:907-14. 2004
    ..Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects...
  47. ncbi Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A
    Hua Wei Wang
    Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
    Mutat Res 643:48-53. 2008
    The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex...
  48. ncbi Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability
    Jacques S Beckmann
    Department of Medical Genetics, University of Lausanne and Centre Hospitalier Universitaire Vaudois, 2 Avenue Pierre Decker, 1011 Lausanne, Switzerland
    Nat Rev Genet 8:639-46. 2007
    ..structural changes constitute a major source of inter-individual genetic variation that could explain variable penetrance of inherited (Mendelian and polygenic) diseases and variation in the phenotypic expression of aneuploidies and ..
  49. pmc Low-penetrance susceptibility variants in familial colorectal cancer
    Iina Niittymäki
    Department of Medical Genetics, Genome Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    Cancer Epidemiol Biomarkers Prev 19:1478-83. 2010
    Genomewide association studies have identified 10 low-penetrance loci that confer modestly increased risk for colorectal cancer (CRC)...
  50. ncbi Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age
    Dorina M Van Der Kolk
    Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Breast Cancer Res Treat 124:643-51. 2010
    ..We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the ..
  51. pmc RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
    José R Valverde
    Servicio de Informática, Centro Nacional de Biotecnologia, CSIC, Campus de Cantoblanco, Madrid, Spain
    BMC Genet 6:53. 2005
    ..The molecular scanning of RB1 in search of germ line mutations lead to the publication of more than 900 mutations whose knowledge is important for genetic counselling and the characterization of phenotypic-genotypic relationships...
  52. ncbi Variable expressivity and high penetrance of CYP1B1 mutations associated with primary congenital glaucoma
    Fatemeh Suri
    School of Biology, University College of Science, University of Tehran, Tehran, Iran
    Ophthalmology 116:2101-9. 2009
    To investigate penetrance and expressivity of CYP1B1 genotypes associated with primary congenital glaucoma (PCG).
  53. ncbi Toll-like receptor 4 gene polymorphism modulates phenotypic expression in patients with hereditary hemochromatosis
    Pierre Alexandre Krayenbuehl
    Division of Internal Medicine, Medical Clinic and Policlinic, University Hospital of Zurich, Zurich, Switzerland
    Eur J Gastroenterol Hepatol 22:835-41. 2010
    Clinical penetrance of hereditary hemochromatosis is highly variable...
  54. ncbi Penetrance and expressivity in the molecular age
    Joel Zlotogora
    Department of Community Genetics, Public Health Services, Ministry of Health, Israel
    Genet Med 5:347-52. 2003
    b>Penetrance and expressivity have been defined through clinical experience. Although penetrance is often seen as the end of the spectrum of expressivity, penetrance and expressivity are considered as distinct phenomena...
  55. ncbi Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000
    Laufey Tryggvadottir
    Icelandic Cancer Registry, Skógarhlío 8, Reykjavik, Iceland
    J Natl Cancer Inst 98:116-22. 2006
    ..Recent results suggest that penetrance has increased in recent birth cohorts...
  56. pmc Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family
    D Gareth Evans
    Academic Unit of Medical Genetics and Regional Genetics Service, St Mary s Hospital Manchester M13 0JH, UK
    BMC Cancer 8:155. 2008
    ..However, considerable controversy exists regarding the cancer risks in women who test positive for the family mutation...
  57. pmc Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population
    Urban Hellman
    Medical and Clinical Genetics, Umea University, Umea, Sweden
    Amyloid 15:181-6. 2008
    ..The present study aims to estimate the penetrance in TTR Val30Met Swedish families...
  58. ncbi Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian families
    M A C Saporta
    Department of Neurology, University Hospital, Federal University of Rio de Janeiro, Brazil
    Eur J Neurol 16:337-41. 2009
    ..Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families.
  59. ncbi The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening
    C Thauvin-Robinet
    Centre de Genetique, Hôpital d Enfants, 10, Bd Maréchal de Lattre de Tassigny, BP 77 908, 21079 Dijon Cedex, France
    J Med Genet 46:752-8. 2009
    ..The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice.
  60. ncbi Inheritance of most X-linked traits is not dominant or recessive, just X-linked
    William B Dobyns
    Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA
    Am J Med Genet A 129:136-43. 2004
    ..We reviewed the literature on 32 X-linked disorders and recorded information on penetrance and expressivity in both sexes...
  61. pmc Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease
    David N Cooper
    Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK
    Hum Genet 132:1077-130. 2013
    ..most if not all features of the disease in question, a phenomenon that is known as 'reduced (or incomplete) penetrance'...
  62. ncbi A novel mutation in CACNA1S gene associated with hypokalemic periodic paralysis which has a gender difference in the penetrance
    Fei Feng Li
    Genomics Research Center, Harbin Medical University, Harbin, China
    J Mol Neurosci 46:378-83. 2012
    ..Clinical analysis demonstrated that the penetrance of the mutation was complete in male carriers, but we did not find evident clinical features in female carriers...
  63. pmc Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes
    John R Giudicessi
    Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN, USA
    Transl Res 161:1-14. 2013
    ..Similar to many Mendelian disorders, the cardiac "channelopathies" exhibit incomplete penetrance, variable expressivity, and phenotypic overlap, whereby genotype-positive individuals within the same genetic ..
  64. pmc Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222
    V Enciso-Mora
    Division of Genetics and Epidemiology, Institute of Cancer Research, 15 Cotswold Road, Surrey SM2 5NG, UK
    Br J Cancer 108:2178-85. 2013
    ..In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma...
  65. pmc The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment
    Jennifer E Cropley
    Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia
    Proc Biol Sci 279:2347-53. 2012
    ..Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype...
  66. ncbi Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis
    Kotaro Ogaki
    Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    Neurobiol Aging 33:2527.e11-6. 2012
    ..The existence of a 76-year-old asymptomatic carrier supported the notion of incomplete penetrance. The C9orf72 mutation should be analyzed in sporadic ALS patients after determining their family histories not ..
  67. 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.
  68. ncbi Prevalence of glucocerebrosidase mutations in the Israeli Ashkenazi Jewish population
    M Horowitz
    Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, Israel
    Hum Mutat 12:240-4. 1998
    ..genotype is much lower than that expected according to the frequency of the N370S mutation, suggesting a low penetrance of this mutation...
  69. ncbi A high-penetrance form of late-onset torsion dystonia maps to a novel locus (DYT21) on chromosome 2q14.3-q21.3
    Nina Norgren
    Unit for Medicine, Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden
    Neurogenetics 12:137-43. 2011
    ..Four pure autosomal dominant dystonia loci have been mapped to date, DYT1, 6, 7, and 13, with varying penetrance. We report the mapping of a novel locus for a late-onset form of pure torsion dystonia in a family from northern ..
  70. ncbi Using reference databases of genetic variation to evaluate the potential pathogenicity of candidate disease variants
    Kevin P Kenna
    Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
    Hum Mutat 34:836-41. 2013
    ..with mutations implicated in amyotrophic lateral sclerosis were higher than what could be accounted for by high-penetrance disease models...
  71. ncbi Gender differences in penetrance and phenotype in hypokalemic periodic paralysis
    Qing Ke
    Department of Neurology, First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
    Muscle Nerve 47:41-5. 2013
    ..Different sex hormones have different effects on ion channels. A comparison of the penetrance and phenotype between males and females with HypoPP mutations should aid in proving that sex hormones play ..
  72. ncbi X-linked transposition of the great arteries and incomplete penetrance among males with a nonsense mutation in ZIC3
    A Megarbane
    Unite de Genetique Medicale, Faculte de Medecine, Université Saint Joseph, Beirut
    Eur J Hum Genet 8:704-8. 2000
    ..To our knowledge, this is the first instance of incomplete penetrance in a male for a mutation in a chromosome X gene.
  73. pmc Estimates of penetrance for recurrent pathogenic copy-number variations
    Jill A Rosenfeld
    Signature Genomic Laboratories, PerkinElmer, Inc, Spokane, Washington, USA
    Genet Med 15:478-81. 2013
    ..of copy-number variations are being identified as susceptibility loci for a variety of pediatric diseases, the penetrance of these copy-number variations remains mostly unknown...
  74. ncbi Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia
    M Walter
    Department of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Tuebingen, Germany
    Neurobiol Dis 38:192-200. 2010
    ..Due to the reduced penetrance of approximately 30-40%, the determination of the mutation in a subject is of limited use with regard to actual ..
  75. ncbi Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory, at the clinic and in the population
    J Sequeiros
    UnIGENe, IBMC Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal
    Clin Genet 78:381-7. 2010
    ..We estimated the frequency of large normal alleles (27-35 CAGs) and of reduced penetrance alleles (36-39 CAGs), as well as the frequency of genotypes carrying them, in (i) a diagnostic laboratory, (ii) ..
  76. ncbi High- and low-penetrance cutaneous melanoma susceptibility genes
    Maria Concetta Fargnoli
    Department of Dermatology, University of L Aquila, Coppito 2, 67100 L Aquila, Italy
    Expert Rev Anticancer Ther 6:657-70. 2006
    ..To date, two high-penetrance melanoma susceptibility genes, cyclin-dependent kinas inhibitor (CDKN)2A on chromosome 9p21 and cyclin-dependent ..
  77. ncbi Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers
    M Anheim
    INSERM, U975, Paris, France
    Neurology 78:417-20. 2012
    Glucocerebrosidase (GBA) gene mutations represent a strong risk factor for Parkinson disease (PD). PD penetrance in GBA mutation carriers, which represents a key issue for genetic counseling, especially for relatives of patients with ..
  78. ncbi A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance
    J A Moolman
    Department of Experimental Cardiology, Max Planck Institute for Physiological and Clinical Research, Bad Nauheim, Germany
    Circulation 101:1396-402. 2000
    ..We report a mutation in the myosin-binding protein-C (MyBP-C) gene, its clinical consequences in a large family, and myocardial tissue findings that may provide insight into the mechanism of disease...
  79. ncbi The RET mutation E768D confers a late-onset familial medullary thyroid carcinoma -- only phenotype with incomplete penetrance: implications for screening and management of carrier status
    Tabib Dabir
    Department of Medical Genetics, Belfast City Hospital Trust, BT9 7AB, Belfast, UK
    Fam Cancer 5:201-4. 2006
    ..This mutation has been described in very few families worldwide and the spectrum of disease and natural history is unclear...
  80. pmc A method for estimating penetrance from families sampled for linkage analysis
    Yuanjia Wang
    Department of Statistics, Columbia University, New York, New York 10027, USA
    Biometrics 62:1081-8. 2006
    ..The purpose here is to present an approach to adjusting for the potential bias while using the families from linkage analysis to estimate the risk...
  81. pmc Age-dependent penetrance of different germline mutations in the BRCA1 gene
    F Al-Mulla
    Department of Pathology, Safat, Kuwait
    J Clin Pathol 62:350-6. 2009
    ..This study addresses whether different exon mutations have variable expressivity especially in relation to the age of onset of breast cancer...
  82. ncbi Do haplogroups H and U act to increase the penetrance of Alzheimer's disease?
    Farzaneh Fesahat
    Khatam University, Tehran, Iran
    Cell Mol Neurobiol 27:329-34. 2007
    ..016 for haplogroup H and P = 0.0003 for haplogroup U), Thus, these two haplogroups might act synergistically to increase the penetrance of AD disease.
  83. ncbi Disease penetrance and risk stratification for sudden cardiac death in asymptomatic hypertrophic cardiomyopathy mutation carriers
    Michelle Michels
    Department of Cardiology, Thoraxcenter, Erasmus MC Rotterdam, The Netherlands
    Eur Heart J 30:2593-8. 2009
    ..To investigate the outcome of cardiac evaluation and the risk stratification for sudden cardiac death (SCD) in asymptomatic hypertrophic cardiomyopathy (HCM) mutation carriers...
  84. pmc Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study
    Oliver W J Quarrell
    J Med Genet 44:e68. 2007
    To obtain penetrance data for Huntington's disease when DNA results are in the range of 36-39 CAG repeats and assess the consistency of reporting the upper allele from two reference centres.
  85. ncbi A new sequence variant in mitochondrial DNA associated with high penetrance of Russian Leber hereditary optic neuropathy
    Nataliya Povalko
    Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi Machi, Kurume, Fukuoka 830 0011, Japan
    Mitochondrion 5:194-9. 2005
    ..in 15 Russian LHON patients and found the new mtDNA sequence variant in one family (2 patients) who showed 100% penetrance of the disease in men...
  86. ncbi Synergistic heterozygosity for TGFbeta1 SNPs and BMPR2 mutations modulates the age at diagnosis and penetrance of familial pulmonary arterial hypertension
    John A Phillips
    Divisions of Medical Genetics, Vanderbilt University School of Medicine, Nashville, Tennessee 27232 2578, USA
    Genet Med 10:359-65. 2008
    ..that functional TGFbeta1 SNPs increase TGFbeta/BMP signaling imbalance in BMPR2 mutation heterozygotes to accelerate the age at diagnosis, increase the penetrance and SMAD2 expression in familial pulmonary arterial hypertension.
  87. ncbi Colorectal cancer susceptibility quantitative trait loci in mice as a novel approach to detect low-penetrance variants in humans: a two-stage case-control study
    Ceres Fernández-Rozadilla
    Galician Public Foundation of Genomic Medicine FPGMX, CIBERER, Genomics Medicine Group, Hospital Clinico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain
    Cancer Epidemiol Biomarkers Prev 19:619-23. 2010
    ..The rest of the susceptibility could be explained by a number of low-penetrance variants following a polygenic model of inheritance...
  88. ncbi Very low penetrance of hearing loss in seven Han Chinese pedigrees carrying the deafness-associated 12S rRNA A1555G mutation
    Xiaowen Tang
    Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China
    Gene 393:11-9. 2007
    ..The penetrance of hearing loss in these pedigrees ranged from 3% to 29%, with an average of 13...
  89. pmc Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model
    Anne Laure Leoni
    INSERM, UMR915, l institut du thorax, Nantes, France
    PLoS ONE 5:e9298. 2010
    ..with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects...
  90. ncbi Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: implication for early detection and prevention of deafness
    Pu Dai
    Department of Otolaryngology, Chinese PLA General Hospital, Beijing, China
    Biochem Biophys Res Commun 340:194-9. 2006
    ..Strikingly, these Chinese pedigrees exhibited extremely low penetrance of hearing loss, ranging from 4% to 18%, with an average of 8%...
  91. ncbi Penetrance analysis of the PALB2 c.1592delT founder mutation
    Hannele Erkko
    Laboratory of Cancer Genetics, Oulu University Hospital, Finland
    Clin Cancer Res 14:4667-71. 2008
    ..In the present study, we wanted to assess in more detail the increased risk (hazard ratio, HR) and the age-specific cumulative risk (penetrance) of c.1592delT with regard to susceptibility to breast and other forms of cancer.
  92. ncbi Molecular basis of low-penetrance retinoblastoma
    J W Harbour
    Washington University, Campus Box 8069, 660 S Euclid Ave, St Louis, MO 63110, USA
    Arch Ophthalmol 119:1699-704. 2001
    ..Most families with hereditary retinoblastoma demonstrate autosomal dominant inheritance with almost complete penetrance and high expressivity...
  93. pmc Overcoming the winner's curse: estimating penetrance parameters from case-control data
    Sebastian Zollner
    Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
    Am J Hum Genet 80:605-15. 2007
    ..After detection of significant association, estimates of penetrance and allele-frequency parameters for the associated variant indicate the importance of that variant and ..
  94. pmc Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees
    Fanny Stutzmann
    Centre National de la Recherche Scientifique 8090, Institute of Biology, Pasteur Institute, Lille, France
    Diabetes 57:2511-8. 2008
    ..However, there is uncertainty regarding the degree of penetrance of this condition, and the putative impact of the environment on the development of obesity in MC4R mutation ..
  95. ncbi Co-occurrence of A1555G and G11778A in a Chinese family with high penetrance of Leber's hereditary optic neuropathy
    A Mei Zhang
    Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Jiaochang Donglu 32, Kunming, Yunnan 650223, China
    Biochem Biophys Res Commun 376:221-4. 2008
    ..Here we reported one three-generation Chinese family with a high penetrance of LHON (78.6%)...
  96. pmc Leber hereditary optic neuropathy
    P Y W Man
    Department of Neurology, School of Neurosciences and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK
    J Med Genet 39:162-9. 2002
    ..This marked incomplete penetrance and gender bias imply that additional mitochondrial and/or nuclear genetic factors must be modulating the ..
  97. pmc A mechanism for low penetrance in an ALS family with a novel SOD1 deletion
    L Zinman
    Centre for Neurodegenerative Diseases, Department of Medicine, University of Toronto, 6 Queen s Park Crescent West, Toronto, Ontario, Canada, M5S 3H2
    Neurology 72:1153-9. 2009
    ..However, due to reduced mutation penetrance, the disease may present in a recessive or sporadic manner.
  98. ncbi Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease
    Koen M A Dreijerink
    Department of Endocrinology, University Medical Centre Utrecht, PO Box 85 500, 3508 GA, Utrecht, The Netherlands
    Eur J Endocrinol 153:741-6. 2005
    ..The penetrance of MEN1 among gene carriers is reported to be high; 82-99% at age 50...
  99. pmc Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population
    I Aksentijevich
    Genetics Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892 1820, USA
    Am J Hum Genet 64:949-62. 1999
    ..Several lines of evidence indicate reduced penetrance among Ashkenazi Jews, especially for E148Q, P369S, and K695R...
  100. pmc Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike
    Jiong Yan
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Am J Hum Genet 80:518-25. 2007
    ..and Df(11)17-1/+, which have 2-Mb and 590-kb deletions, respectively, and Rai1(-/+)--revealed that the penetrance of the craniofacial phenotype appears to be influenced by deletion size and genetic background...
  101. pmc Prevalence and novelty of PRPF31 mutations in French autosomal dominant rod-cone dystrophy patients and a review of published reports
    Isabelle Audo
    INSERM, UMRS968, Paris, F 75012, France
    BMC Med Genet 11:145. 2010
    ....

Research Grants72

  1. Exome re-sequencing candidate loci for familial essential tremor
    Barry E Kosofsky; Fiscal Year: 2012
    ..ET is inherited as a dominant trait with incomplete penetrance in most familial cases but complex multi-genic transmission is possible...
  2. Characterization of epsilon-sarcoglycan interacting proteins in mouse brain
    Yuqing Li; Fiscal Year: 2012
    ..or hereditary (alcohol-responsive) myoclonic dystonia, is an autosomal dominant dystonia with incomplete penetrance. Zimprich and colleagues first identified loss-of-function mutations in a gene coding for ?-sarcoglycan (?-SG;..
  3. Nanomedicine and NeuroAIDS
    Howard E Gendelman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Drug toxicities, patient compliance and limited penetrance into viral reservoirs (notably the central nervous system (CNS), gut and lymphatic organs) have diminished long-term antiretroviral therapy (..
  4. Molecular Studies of Bone Marrow Failure
    Monica Bessler; Fiscal Year: 2013
    ..During our last funding period we investigated the frequency, heritability, penetrance, and expressivity of mutations in TERC and in the telomerase catalytic subunit TERT in patients diagnosed with ..
  5. Determinants of Disease Expression in Arrhythmogenic Cardiomyopathy
    Jeffrey E Saffitz; Fiscal Year: 2010
    ..to other familial non-ischemic cardiomyopathies, ARVC is characterized by far greater variability in genetic penetrance and disease manifestation1...
  6. Pharmacology of Antiretroviral Nanoparticle Micelles
    Christopher J Destache; Fiscal Year: 2010
    ..The nanoformulations will be used as a drug delivery system to improve tissue penetrance of ART into the reticuloendothelial system (RES;spleen, liver, lymph nodes) in mice...
  7. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2013
    ..Strain-dependence of murine phenotypes mimics the variable penetrance and disease expression characteristic of human monogenic epilepsies including those caused by mutant NaV ..
  8. Mitochondrial Inborn Errors in Metabolism
    Douglas C Wallace; Fiscal Year: 2013
    ..degeneration with males being 2 to 5 times more likely to be affected than females and with a highly variable penetrance. Because of the unique tissue specificity of LHON, an animal model is required to investigate the neuronal, RGC ..
  9. Mitochondrial Roles of the SUV3 in Premature Aging and Cancer
    Wen Hwa Lee; Fiscal Year: 2012
    ..characterized by a shortened life span and predisposition to a broad spectrum of tumors with 90% penetrance, suggesting that SUV3 is a novel tumor suppressor...
  10. Mouse Models to Characterize the Role of Lrp6 in Metabolic Syndrome
    Bart O Williams; Fiscal Year: 2010
    ..This will direct expression specifically and with high penetrance to the liver...
  11. Mechanisms linking RAS signals to disordered hematopoiesis and myeloid neoplasia
    BENJAMIN BRAUN; Fiscal Year: 2013
    ..This is characterized by profound myelomonocytic proliferation, severe anemia, early death and complete penetrance. Pathogenic bone marrow progenitors in KrasD12 mice demonstrate: (1) biased differentiation that favors the ..
  12. Cthrc1 function as a novel TGF-beta antagonist in the vasculature
    Volkhard Lindner; Fiscal Year: 2013
    ..Thus Cthrc1 is an essential molecule with partial penetrance of lethal haploinsufficiency...
  13. Murine Models for Mantle Cell Lymphoma: The role of tumor initiating cells (TIC)
    Richard J Ford; Fiscal Year: 2010
    ..DTG mice stochastically develop NHL-B resembling aggressive MCL-BV by 3-4 months (100% penetrance), allowing for sequential and defined patho-physiologic characterization of molecular and genotypic alterations ..
  14. BRCA1 and progesterone receptors in breast cancer
    Eva Y Lee; Fiscal Year: 2013
    ..The short latency, complete penetrance and similarity with human breast etiology make this mouse model very valuable...
  15. Genetic contributors to diabetes and dyslipidemia in African Americans
    Michele M Sale; Fiscal Year: 2010
    ..We postulate that this unique combination of ancestral and environmental factors results in a more consistent penetrance of diabetes risk alleles, as well as enrichment of risk alleles of African origin...
  16. Glypican-1 in gliomagenesis
    Andreas Friedl; Fiscal Year: 2013
    ..express activated ras oncogene in a astrocyte-specific manner and which develop high-grade gliomas with high penetrance and short latency. These experiments will reveal whether GPC1-deficient animals are protected from gliomagenesis...
  17. Structure/Function of Steroid Transforming AKR's
    Trevor M Penning; Fiscal Year: 2011
    ..Non-synonymous high penetrance SNPs will be introduced into AKR1C4 to determine whether these allelic variants affect enzyme function or ..
  18. Inhibition of HIV-Induced Synaptodentritic Damage
    Val S Goodfellow; Fiscal Year: 2013
    ..penetrant antiviral drugs may be counter-productive, since it has been shown that antiretrovirals with good CNS penetrance are associated with impaired neurocognitive function...
  19. Epidemiologic Study of Hepatocellular Carcinoma in the US
    Herbert Yu; Fiscal Year: 2013
    ..Evidence also indicates significant host susceptibility to HCC reflected by low penetrance single nucleotide polymorphisms involved in regulation of cell proliferation, apoptosis, immune response to ..
  20. Plasminogen activator inhibitor-1 in tumor progression and metastasis
    Yves A DeClerck; Fiscal Year: 2013
    ..of PAI-1 suppression on tumor initiation in PAI-1 null mice crossed with transgenic NB-Tag mice that have a 100% penetrance in neuroblastoma tumor formation...
  21. Hemochromatosis - Epidemiology and Molecular Mechanisms
    Pauline L Lee; Fiscal Year: 2010
    ..the regulation of iron absorption is inherited epigenetically, this finding would not only explain the variable penetrance of hemochromatosis, but would greatly alter our perception of how natural selection functions over the span of ..
  22. GENETIC STUDIES OF ODDD
    Ethylin Wang Jabs; Fiscal Year: 2010
    Oculodentodigital dysplasia (ODDD) is a syndrome with an autosomal dominant pattern of inheritance, high penetrance, and variable expressivity. The phenotype includes dental, craniofacial, ocular, hand, and foot abnormalities...
  23. Trajectories and Markers of Neurodegeneration in Fragile X Premutation Carriers
    Susan M Rivera; Fiscal Year: 2013
    ..The disease has a variable and age-related penetrance, affecting 75% of male premutation carriers by the eighth decade of life...
  24. Epi)Genomic drivers of primary and metastatic pancreatic islet cell carcinoma
    DOMINIC JAMES SMIRAGLIA; Fiscal Year: 2013
    ..The predominant neoplasia observed is an islet cell carcinoma, expressing glucagon, which arises with high penetrance and exhibits symptoms and profound metastatic spread to sites representative of the human disease, resulting in ..
  25. Serum Biomarkers Associated With Phenotypic Expression of Hemochromatosis.
    Kris Kowdley; Fiscal Year: 2013
    ..However, there is only partial penetrance of this mutation and many C282Y homozygotes are asymptomatic...
  26. Monoallelic expression in neurons derived from induced pluripotent stem cells
    Herbert M Lachman; Fiscal Year: 2013
    ..epidemiological features of neuropsychiatric disorders, such as discordance in monozygotic twins and reduced penetrance. Two experimental tools have emerged that provide the means to evaluate the role of monoallelic (also known as ..
  27. Identification and Characterization of the Mouse PPCD1 Gene
    Christopher A Bradfield; Fiscal Year: 2013
    ..The mouse PPCD1 phenotype exhibits an autosomal dominant pattern of inheritance, with complete penetrance on the sensitive DBA/2J background and significantly decreased penetrance on the C57BL/6J background...
  28. Disease Mechanisms in ARVC
    Jeffrey E Saffitz; Fiscal Year: 2013
    ..mechanisms that are likely to apply to more common forms of heart disease;and it's highly variable genetic penetrance indicates the presence of powerful modifiers of the risk of sudden death...
  29. Sex-specific genetic architecture of irritable bowel syndrome
    Lisa A Kilpatrick; Fiscal Year: 2013
    ..have largely overlooked sex of the subject as an important variable despite the fact that sex can modify both penetrance and expressivity of a wide variety of complex traits...
  30. Second-hit and sexual dimorphism effects in PAH
    Pravin B Sehgal; Fiscal Year: 2013
    ..However, disease development, even in FPAH with known mutations in BMPRII, has low (10-15%) penetrance leading to searches for candidate "second-hit" genes that might be involved...
  31. Molecular Mechanisms of Histone Acetyltransferases
    John M Denu; Fiscal Year: 2012
    ..epigenetic process can explain how genetically equivalent stem cells differentiate into diverse cell types, how penetrance of disease is modulated by nutrition and environment, and how organogenesis, tissue formation, and aging occur...
  32. B7-based, CD28 or CTLA-4-specific agonists and antagonists for tolerance inductio
    Roland K Strong; Fiscal Year: 2013
    ..biological half-lives to reduce immune related adverse events and minimal molecular weights to maximize tissue penetrance. The immediate goal of the exploratory/developmental phase of this project (this R21 application) is to ..
  33. Genetics and biology of a viable mutant mouse with dystonic movements
    Kathleen J Sweadner; Fiscal Year: 2013
    ..The mouse has the unusual properties for a neurological mutation of showing dominant inheritance with high penetrance;adult-onset;a lack of incapacitating deficits;lifespan of at least 18 months so far;and easy breeding...
  34. Pax genes in cardiac development
    ZACHARY PAUL NEEB; Fiscal Year: 2012
    ..our preliminary data reveal that Pax7 systemic mutants on a Pax3Hypo background (Pax7-/-;Pax3Hypo) develop 100% penetrance of PTA and VSD...
  35. Second-site genetic modifiers of CTG/CAG microsatellite stability
    Michael Leffak; Fiscal Year: 2013
    ..of CTG/CAG expansion is linked to increased disease severity and earlier age of onset of symptoms, but the penetrance of DM1 varies widely...
  36. Replication Licensing in Genome Stability, Cancer and Aging
    Steven C Pruitt; Fiscal Year: 2013
    ..These mice are remarkably cancer prone and exhibit complete penetrance of thymic lymphoblastic lymphoma on the 129Sv genetic background on which it was constructed...
  37. Role of Gender-associated Microbiota in Organ-specific Autoimmunity
    Martin A Kriegel; Fiscal Year: 2013
    ..However, the absence of microbiota under germ-free conditions leads to 100% penetrance of the phenotype in both genders...
  38. Sodium Channels and Cardiac Arrhythmias
    Isabelle Deschenes; Fiscal Year: 2013
    ..Syndrome (BrS) which are autosomal dominant diseases, these more common arrhythmias also display variable penetrance. There are several prevailing hypotheses that have attempted to explain why a particular gene expression pattern ..
  39. Synaptic target selection in Drosophila
    KAI G ZINN; Fiscal Year: 2013
    ..We found 30 genes whose expression on all muscles causes high-penetrance axonal mistargeting phenotypes but does not perturb muscle structure...
  40. Genetic Complexity and Modifiers of Hirschsprung Disease
    E Michelle Southard-Smith; Fiscal Year: 2011
    ..Family members carrying identical gene mutations often exhibit differences in penetrance and length of gut lacking enteric neurons...
  41. MOLECULAR ETIOLOGY OF EARLY ONSET TORSION DYSTONIA
    XANDRA OWENS BREAKEFIELD; Fiscal Year: 2013
    ..Specifically Dr. Ozelius (Project 1) will focus on identifying genes responsible for penetrance in DYT1 and additional genes underlying non-DYT1 early onset dystonia, as well as variations in these early ..
  42. Modeling TAR Microdeletion Syndrome in Mouse
    Christa Lese Martin; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Copy number variation (CNV) syndromes with low penetrance represent a new challenge to understanding and predicting disease manifestation...
  43. RECEPTOR DIVERSITY IN RECOGNITION OF INFLUENZA HA
    Andrew J Caton; Fiscal Year: 2012
    ..Moreover, the penetrance of arthritis could be modulated by varying the reactivity of CD4+ T cells for the HA, since the majority of mice ..
  44. Discover and functionally characterize full-penetrance causes of nephrosis/FSGS
    Friedhelm Hildebrandt; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Discover and functionally characterize full-penetrance causes of nephrosis/FSGS...
  45. APOL1 variants: Understanding the basis of disparities in rates of kidney disease
    Martin R Pollak; Fiscal Year: 2013
    ..We will define structural variants that may alter APOL1 gene expression, and test their effects on the penetrance of the two disease-causing alleles...
  46. Genetic Mouse Models of Glioma
    Luis F Parada; Fiscal Year: 2013
    ..mutant mice develop tumors that histologically and molecularly resemble human astrocytomas with 100% penetrance. In the present application, we propose experiments designed to investigate the cell(s) of tumor origin and to ..
  47. Role of the PDGF signaling pathway in pulmonary artery hypertension
    Akiko Hata; Fiscal Year: 2013
    ..encoding the bone morphogenetic protein (BMP) type II receptor (BMPRII) are associated with PAH(4-6), however a penetrance of BMPRII mutations is limited to ~20%, indicating that there are other factors contribute to the development of ..
  48. Genetic Predisposition To Thoracic Aortic Aneurysms/Dissections
    Dianna M Milewicz; Fiscal Year: 2013
    ..TAAD is inherited in an autosomal dominant manner with variable expression and decreased penetrance in up to 20% of TAAD patients (Familial TAAD)...
  49. Induced Pluripotent Stem Cells for the Study of Long QT Syndrome
    ERIC DAVID ADLER; Fiscal Year: 2013
    ..Many mutations have been identified that cause inherited long QT syndrome, but genotypes demonstrate incomplete penetrance. Hence, genetic testing lacks prognostic value...
  50. Impact of Presenilin 2 Mutation and Deficiency on Microglial Function
    Suman Jayadev; Fiscal Year: 2010
    ..Presenilin 1 (PS1) and Presenilin 2 (PS2), in which mutations lead to autosomal dominant AD with nearly complete penetrance. Recent literature and our preliminary studies suggest that the presenilins and the ?-secretase complex play a ..
  51. THE GENETIC ARCHITECTURE OF CONGENITAL HEART DISEASE
    Patrick Y Jay; Fiscal Year: 2013
    ..Our long term goal hence is to dissect the basis of incomplete penetrance and phenotypic pleiotropy...
  52. Molecular Epidemiology of NHL and CLL
    James R Cerhan; Fiscal Year: 2012
    ..for several candidate susceptibility genes in the etiology of NHL, supporting a polygenic model based on low-penetrance alleles in line with the common-variant, common- disease hypothesis...
  53. Novel SIV Model of HAND
    Joseph L Mankowski; Fiscal Year: 2013
    ..very similar to HAART in HIV-infected individuals, combining classes of antiretroviral drugs that have low CNS penetrance. The value of this model is: 1) Both CD4+ T cells and monocyte/macrophages are infected, 2) tissues including ..
  54. Modeling Neurodegeneration and Adrenoleukodystrophy in Drosophila
    Anthea Letsou; Fiscal Year: 2010
    ..X-ALD is a clinically heterogeneous disorder, exhibiting incomplete penetrance and variable expressivity...
  55. HISTONE H3 METHYLATION AND EPIGENOMICS IN ACUTE LEUKEMIA
    Lukas D Wartman; Fiscal Year: 2013
    ..growth, differentiation, and self renewal, and we will determine whether Kdm6a deficiency alters APL latency, penetrance, or phenotype in a tumor watch study...
  56. EPIDEMIOLOGY OF SURFACTANT PROTEIN-B DEFICIENCY
    FRANCIS SESSIONS COLE; Fiscal Year: 2013
    ..and ABCA3), and natural selection against variants that disrupt neonatal lung function suggest that rare, high penetrance alleles of independent origin in multiple candidate genes and gene pathways account for missing disease ..
  57. Combined Approach to Genetic Modifiers of Inherited Epilepsy
    Jennifer A Kearney; Fiscal Year: 2013
    ..Within these genetic epilepsies, there is variable penetrance and expressivity of the clinical phenotype, suggesting a role for genetic modifiers...
  58. Understanding the role of TREX1 in the innate immunity and autoimmune diseases
    Nan Yan; Fiscal Year: 2012
    ..High penetrance causes of lupus are rare and therefore important to study because they have the potential to provide immediate ..
  59. Role of SFTPC in Pathogenesis of Interstitial Lung Disease
    TIMOTHY EDWARD WEAVER; Fiscal Year: 2013
    ..for less than 5% of total IPF cases and are characterized by autosomal dominant inheritance with variable penetrance related to the influence of both genetic modifiers and environmental factors...
  60. Mice Harboring Human DISC1-Boymaw Fusion Transcripts
    XIANJIN ZHOU; Fiscal Year: 2010
    ..However, there are a few well defined functional mutations identified with high penetrance in schizophrenia families...
  61. Integrated Care Clinics for IDUs in India: a cluster randomized trial
    Shruti H Mehta; Fiscal Year: 2013
    ..1 million injection drug users (IDUs). Data from our group and others show poor penetrance of voluntary counseling and testing (VCT) and risk-reduction services among IDUs, as well as late HIV diagnosis, ..
  62. Single Centriole-Mediated Gynogenesis in the Zebrafish
    Francisco J Pelegri; Fiscal Year: 2012
    ..In Aim 1 we will test the effect of various genetic backgrounds on the penetrance of the paternal cea phenotype...
  63. GENETIC PREDISPOSITION TESTING IN COLORECTAL CANCER
    Deborah Schrag; Fiscal Year: 2003
    ..A recently described low-penetrance germline mutation in codon I1307K of the APC gene that appears to increase colorectal cancer risk among ..
  64. Do estrogen receptors in B cells and DC mediate sex bias in murine lupus?
    Susan Kovats; Fiscal Year: 2009
    ..The Sle1 and Sle3 lupus susceptibility loci present in NZM2410 mice direct increased penetrance of disease in females, which is consistent with studies showing that elevation of systemic estradiol or exposure ..
  65. Nuclear modifier genes for maternally inherited deafness
    Min Xin Guan; Fiscal Year: 2010
    ..Mitochondrial 12S rRNA A1555G mutation has been found in many families of various ethnic origins with variable penetrance and expressivity of aminoglycoside-induced and non-syndromic hearing loss...
  66. Molecular Foundations of the Myoclonus-Dystonia Syndrome
    Mark leDoux; Fiscal Year: 2006
    ..Rarely, dystonia may be the only phenotypic manifestation of the disease in an affected family member. Penetrance is incomplete and expressivity is variable both within and among families...
  67. Genetic modifiers of hemochromatosis phenotype
    Dorota Gertig; Fiscal Year: 2006
    ..b>Penetrance is age-dependent and it is estimated that only about half of all C282Y homozygotes will express clinical disease...
  68. APPLYING GENOME MISMATCH SCANNING TO THE HUMAN GENOME
    Patrick Brown; Fiscal Year: 1999
    ..that are relatively common in the population, heterogeneous in etiology,or that result from alleles with low penetrance, represents a principal challenge at the frontier of human genetics...
  69. Antioxidant Therapy for Ataxia Telangiectasia
    ROBERT SCHIESTL; Fiscal Year: 2009
    ATM (ataxia telangiectasia mutated) heterozygosity seems to be a risk factor for cancer. Even though the penetrance seems to be low, because of the high prevalence of 1-5% in the human population, the population risk is higher than for ..
  70. PULMONARY HYPERTENSION--MECHANISMS AND FAMILY REGISTRY
    James Loyd; Fiscal Year: 2003
    ..of 72 families, FPPH has been shown to be inherited as an autosomal dominant disorder, with incomplete penetrance and genetic anticipation...
  71. Ocular Dysgenesis in Agrin Transgenic Mice
    Robert Burgess; Fiscal Year: 2007
    ..The phenotype is also strain dependent, occurring only in a C57BL/6 genetic background, but with complete penetrance in that strain...
  72. FAMILIAL PULMONARY FIBROSIS
    David Riley; Fiscal Year: 1992
    ..The mode of inheritance is compatible with that of an autosomal dominant gene with variable penetrance. The overall goal of this proposal is to study the molecular genetics of familial pulmonary fibrosis...