The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Penetrance


Psychiatry related information on Penetrance


High impact information on Penetrance

  • The NOD allele at Idd1 does not behave as a recessive diabetes susceptibility gene, as it was originally thought to be, but instead it acts as a dominant gene with varying degrees of penetrance for the phenotypes of insulitis, a prediabetic inflammatory lesion, and spontaneous diabetes [11].
  • Because all 38 FOX proteins and all 8 STOX1 homologs have either tyrosine or phenylalanine at position 153, the predominant Y153H variation is highly mutagenic by conservation criteria but subject to incomplete penetrance [12].
  • Inheritance seems to be oligogenic, with genotype at BAAT modifying penetrance in individuals homozygous with respect to the mutation in TJP2 [13].
  • The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality [14].
  • Familial PPH (FPPH) segregates as an autosomal dominant disorder with reduced penetrance and has been mapped to a locus designated PPH1 on 2q33, with no evidence of heterogeneity [15].

Chemical compound and disease context of Penetrance

  • RESULTS: Depending on the assumed penetrance of the BRCA mutation, compared with surveillance alone, 30-year-old early-stage breast cancer patients with BRCA mutations gain in LE 0.4 to 1.3 years from tamoxifen therapy, 0.2 to 1.8 years from PO, and 0.6 to 2.1 years from PCM [16].
  • We suggest that specific mutations in cysteine codons 618 and 620 result in MEN 2A or FMTC, but can also predispose to HSCR with low penetrance [17].
  • Although the degree of pleocytosis correlated poorly with penetrance, ventricular fluid glucose levels correlated inversely with penetrance of nafcillin (r = -0.7275, P less than 0.001) [18].
  • Segregation analysis of these families leads to the conclusion that coronal synostosis is transmitted as a dominant disorder with 0.60 penetrance and 61% of sporadic cases [19].
  • Results from DNA-marker studies were combined with information from clinical, ophthalmological and electromyographic examinations, with age-dependent penetrance and a recombinant frequency of 4% between the genes for myotonic dystrophy and apolipoprotein C2 being taken into account [20].

Biological context of Penetrance

  • Identification of specific genetic loci that contribute to susceptibility to rheumatoid arthritis (RA) in humans has been hampered by several factors, including: i) multiple interacting genetic loci contributing to susceptibility; ii) complex interactions of environmental and genetic factors; iii) genetic heterogeneity; and iv) low penetrance [21].
  • The penetrance of the multivulva phenotype caused by loss-of-function mutations in lin-15, and gain-of-function mutations in let-23 or let-60 ras, was reduced by ptp-2(op194) [22].
  • However, the penetrance of heterozygous germline mutations in PMS2 is considerably lower than that of mutations in other MMR genes [23].
  • Epigenetic mechanisms are probably involved in many MHC-associated phenomena, including autoimmunity, and appear to be the best explanation for incomplete penetrance [24].
  • Using multipoint linkage analysis between schizophrenia and a genetic map that includes the DRD2 locus and assuming a dominant mode of inheritance, we were able to exclude the DRD2 locus with a lod score of -4.14 for the penetrance of 0.72 and with a lod score of -3.05 for the lower bound penetrance of 0.56 [25].

Anatomical context of Penetrance


Associations of Penetrance with chemical compounds

  • We used the pedigree information to estimate penetrance using the MENDEL program [31].
  • Our findings point to incomplete penetrance of the Rhmod mutation, in the form of "leaky" translation, leading to some posttranslational defects affecting the structure, interaction, and processing of Rh50 glycoprotein [32].
  • This study suggests an important role for uracil misincorporation and resultant chromosomal damage in the pathogenesis of ALL, and that genetic interactions involving low penetrance polymorphisms in folate-metabolizing genes may increase ALL risk [33].
  • Some remarkable clinical features were observed in a large hypoPP family carrying an SCN4A mutation: a complete penetrance in men and women, an early age at onset, postcritic myalgias and an increased number and severity of attacks induced by acetazolamide [34].
  • This polymorphism (valine to methionine at codon 158) has been previously reported to influence the activity of COMT by three to four-fold and has recently been reported to be associated with OCD.1 We tested for linkage using an autosomal dominant model with reduced penetrance and non-parametric methods [35].

Gene context of Penetrance

  • However, the lack of genotype-phenotype correlation, the low penetrance and the sex-dependent effect of RET mutations supported the existence of one or more modifier gene(s) in familial HSCR [36].
  • While these defects are partially penetrant in embryos lacking either fz or Dfz2, the penetrance is significantly enhanced in embryos lacking both [37].
  • However, mouse models of MB, regardless of their initiating lesions, generally depend upon p53 inactivation for rapid onset and high penetrance [38].
  • Coinactivation of Ink4c and p53 provided cultured GNPs with an additive proliferative advantage, either in the presence or absence of Shh, and induced MB with low penetrance but with greatly increased incidence following postnatal irradiation [38].
  • Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population [39].

Analytical, diagnostic and therapeutic context of Penetrance


  1. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Roa, B.B., Boyd, A.A., Volcik, K., Richards, C.S. Nat. Genet. (1996) [Pubmed]
  2. Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus. Phelan, C.M., Rebbeck, T.R., Weber, B.L., Devilee, P., Ruttledge, M.H., Lynch, H.T., Lenoir, G.M., Stratton, M.R., Easton, D.F., Ponder, B.A., Cannon-Albright, L., Larsson, C., Goldgar, D.E., Narod, S.A. Nat. Genet. (1996) [Pubmed]
  3. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Gouya, L., Puy, H., Robreau, A.M., Bourgeois, M., Lamoril, J., Da Silva, V., Grandchamp, B., Deybach, J.C. Nat. Genet. (2002) [Pubmed]
  4. The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Sibilia, M., Fleischmann, A., Behrens, A., Stingl, L., Carroll, J., Watt, F.M., Schlessinger, J., Wagner, E.F. Cell (2000) [Pubmed]
  5. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Chin, L., Pomerantz, J., Polsky, D., Jacobson, M., Cohen, C., Cordon-Cardo, C., Horner, J.W., DePinho, R.A. Genes Dev. (1997) [Pubmed]
  6. The ETS factor TEL2 is a hematopoietic oncoprotein. Carella, C., Potter, M., Bonten, J., Rehg, J.E., Neale, G., Grosveld, G.C. Blood (2006) [Pubmed]
  7. Genomic imprinting: a possible mechanism for the parental origin effect in Huntington's chorea. Reik, W. J. Med. Genet. (1988) [Pubmed]
  8. Spontaneous pneumothorax associated with tuberous sclerosis. Babcock, T.L., Snyder, B.A. J. Thorac. Cardiovasc. Surg. (1982) [Pubmed]
  9. Leber hereditary optic neuropathy. Man, P.Y., Turnbull, D.M., Chinnery, P.F. J. Med. Genet. (2002) [Pubmed]
  10. Caring for the carers: quality of life in Huntington's disease. Aubeeluck, A. British journal of nursing (Mark Allen Publishing) (2005) [Pubmed]
  11. Genetic control of autoimmune diabetes in the NOD mouse. Wicker, L.S., Todd, J.A., Peterson, L.B. Annu. Rev. Immunol. (1995) [Pubmed]
  12. Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family. van Dijk, M., Mulders, J., Poutsma, A., Könst, A.A., Lachmeijer, A.M., Dekker, G.A., Blankenstein, M.A., Oudejans, C.B. Nat. Genet. (2005) [Pubmed]
  13. Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Carlton, V.E., Harris, B.Z., Puffenberger, E.G., Batta, A.K., Knisely, A.S., Robinson, D.L., Strauss, K.A., Shneider, B.L., Lim, W.A., Salen, G., Morton, D.H., Bull, L.N. Nat. Genet. (2003) [Pubmed]
  14. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Chen, B., Bronson, R.T., Klaman, L.D., Hampton, T.G., Wang, J.F., Green, P.J., Magnuson, T., Douglas, P.S., Morgan, J.P., Neel, B.G. Nat. Genet. (2000) [Pubmed]
  15. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Lane, K.B., Machado, R.D., Pauciulo, M.W., Thomson, J.R., Phillips, J.A., Loyd, J.E., Nichols, W.C., Trembath, R.C. Nat. Genet. (2000) [Pubmed]
  16. Life expectancy gains from cancer prevention strategies for women with breast cancer and BRCA1 or BRCA2 mutations. Schrag, D., Kuntz, K.M., Garber, J.E., Weeks, J.C. JAMA (2000) [Pubmed]
  17. Diverse phenotypes associated with exon 10 mutations of the RET proto-oncogene. Mulligan, L.M., Eng, C., Attié, T., Lyonnet, S., Marsh, D.J., Hyland, V.J., Robinson, B.G., Frilling, A., Verellen-Dumoulin, C., Safar, A. Hum. Mol. Genet. (1994) [Pubmed]
  18. Penetrance of nafcillin into human ventricular fluid: correlation with ventricular pleocytosis and glucose levels. Yogev, R., Schultz, W.E., Rosenman, S.B. Antimicrob. Agents Chemother. (1981) [Pubmed]
  19. Genetic study of nonsyndromic coronal craniosynostosis. Lajeunie, E., Le Merrer, M., Bonaïti-Pellie, C., Marchac, D., Renier, D. Am. J. Med. Genet. (1995) [Pubmed]
  20. Presymptomatic testing for myotonic dystrophy by means of the linked DNA marker APOC2. Haan, E.A., Mulley, J.C., Gedeon, A.K., Sheffield, L.J., Sutherland, G.R. Med. J. Aust. (1988) [Pubmed]
  21. A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats. Remmers, E.F., Longman, R.E., Du, Y., O'Hare, A., Cannon, G.W., Griffiths, M.M., Wilder, R.L. Nat. Genet. (1996) [Pubmed]
  22. The Caenorhabditis elegans SH2 domain-containing protein tyrosine phosphatase PTP-2 participates in signal transduction during oogenesis and vulval development. Gutch, M.J., Flint, A.J., Keller, J., Tonks, N.K., Hengartner, M.O. Genes Dev. (1998) [Pubmed]
  23. Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Truninger, K., Menigatti, M., Luz, J., Russell, A., Haider, R., Gebbers, J.O., Bannwart, F., Yurtsever, H., Neuweiler, J., Riehle, H.M., Cattaruzza, M.S., Heinimann, K., Schär, P., Jiricny, J., Marra, G. Gastroenterology (2005) [Pubmed]
  24. The genetics of HLA-associated disease. Larsen, C.E., Alper, C.A. Curr. Opin. Immunol. (2004) [Pubmed]
  25. No linkage between D2 dopamine receptor gene region and schizophrenia. Moises, H.W., Gelernter, J., Giuffra, L.A., Zarcone, V., Wetterberg, L., Civelli, O., Kidd, K.K., Cavalli-Sforza, L.L., Grandy, D.K., Kennedy, J.L. Arch. Gen. Psychiatry (1991) [Pubmed]
  26. Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements. Lee, M.P., Hu, R.J., Johnson, L.A., Feinberg, A.P. Nat. Genet. (1997) [Pubmed]
  27. Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. Cuppens, H., Lin, W., Jaspers, M., Costes, B., Teng, H., Vankeerberghen, A., Jorissen, M., Droogmans, G., Reynaert, I., Goossens, M., Nilius, B., Cassiman, J.J. J. Clin. Invest. (1998) [Pubmed]
  28. Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice. Cheung, W.C., Kim, J.S., Linden, M., Peng, L., Van Ness, B., Polakiewicz, R.D., Janz, S. J. Clin. Invest. (2004) [Pubmed]
  29. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. Yang, F.C., Ingram, D.A., Chen, S., Hingtgen, C.M., Ratner, N., Monk, K.R., Clegg, T., White, H., Mead, L., Wenning, M.J., Williams, D.A., Kapur, R., Atkinson, S.J., Clapp, D.W. J. Clin. Invest. (2003) [Pubmed]
  30. Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Girelli, D., Bozzini, C., Roetto, A., Alberti, F., Daraio, F., Colombari, R., Olivieri, O., Corrocher, R., Camaschella, C. Gastroenterology (2002) [Pubmed]
  31. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Pharoah, P.D., Guilford, P., Caldas, C. Gastroenterology (2001) [Pubmed]
  32. Rhmod syndrome: a family study of the translation-initiator mutation in the Rh50 glycoprotein gene. Huang, C., Cheng, G.J., Reid, M.E., Chen, Y. Am. J. Hum. Genet. (1999) [Pubmed]
  33. Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia. Skibola, C.F., Smith, M.T., Hubbard, A., Shane, B., Roberts, A.C., Law, G.R., Rollinson, S., Roman, E., Cartwright, R.A., Morgan, G.J. Blood (2002) [Pubmed]
  34. Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Sternberg, D., Maisonobe, T., Jurkat-Rott, K., Nicole, S., Launay, E., Chauveau, D., Tabti, N., Lehmann-Horn, F., Hainque, B., Fontaine, B. Brain (2001) [Pubmed]
  35. Catechol-O-methyltransferase and Gilles de la Tourette syndrome. Barr, C.L., Wigg, K.G., Sandor, P. Mol. Psychiatry (1999) [Pubmed]
  36. Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease. Salomon, R., Attié, T., Pelet, A., Bidaud, C., Eng, C., Amiel, J., Sarnacki, S., Goulet, O., Ricour, C., Nihoul-Fékété, C., Munnich, A., Lyonnet, S. Nat. Genet. (1996) [Pubmed]
  37. frizzled and frizzled 2 play a partially redundant role in wingless signaling and have similar requirements to wingless in neurogenesis. Bhat, K.M. Cell (1998) [Pubmed]
  38. The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation. Uziel, T., Zindy, F., Xie, S., Lee, Y., Forget, A., Magdaleno, S., Rehg, J.E., Calabrese, C., Solecki, D., Eberhart, C.G., Sherr, S.E., Plimmer, S., Clifford, S.C., Hatten, M.E., McKinnon, P.J., Gilbertson, R.J., Curran, T., Sherr, C.J., Roussel, M.F. Genes Dev. (2005) [Pubmed]
  39. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. Boyd, J., Sonoda, Y., Federici, M.G., Bogomolniy, F., Rhei, E., Maresco, D.L., Saigo, P.E., Almadrones, L.A., Barakat, R.R., Brown, C.L., Chi, D.S., Curtin, J.P., Poynor, E.A., Hoskins, W.J. JAMA (2000) [Pubmed]
  40. Hoxb8 is required for normal grooming behavior in mice. Greer, J.M., Capecchi, M.R. Neuron (2002) [Pubmed]
  41. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Ford, D., Easton, D.F., Peto, J. Am. J. Hum. Genet. (1995) [Pubmed]
  42. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. Kramer, J.L., Velazquez, I.A., Chen, B.E., Rosenberg, P.S., Struewing, J.P., Greene, M.H. J. Clin. Oncol. (2005) [Pubmed]
  43. Elevated expression of p63 protein in human esophageal squamous cell carcinomas. Hu, H., Xia, S.H., Li, A.D., Xu, X., Cai, Y., Han, Y.L., Wei, F., Chen, B.S., Huang, X.P., Han, Y.S., Zhang, J.W., Zhang, X., Wu, M., Wang, M.R. Int. J. Cancer (2002) [Pubmed]
  44. Familial partial epilepsy with variable foci in a Dutch family: clinical characteristics and confirmation of linkage to chromosome 22q. Callenbach, P.M., van den Maagdenberg, A.M., Hottenga, J.J., van den Boogerd, E.H., de Coo, R.F., Lindhout, D., Frants, R.R., Sandkuijl, L.A., Brouwer, O.F. Epilepsia (2003) [Pubmed]
WikiGenes - Universities