{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T04:08:54Z","timestamp":1759205334019},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,6,29]],"date-time":"2010-06-29T00:00:00Z","timestamp":1277769600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2010,12]]},"DOI":"10.1186\/1752-0509-4-93","type":"journal-article","created":{"date-parts":[[2010,6,30]],"date-time":"2010-06-30T06:13:46Z","timestamp":1277878426000},"source":"Crossref","is-referenced-by-count":10,"title":["The role of noise and positive feedback in the onset of autosomal dominant diseases"],"prefix":"10.1186","volume":"4","author":[{"given":"William J","family":"Bosl","sequence":"first","affiliation":[]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,6,29]]},"reference":[{"key":"482_CR1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/35101031","volume":"1","author":"AG Knudson","year":"2001","unstructured":"Knudson AG: Two genetic hits (more or less) to cancer. Nat Rev Cancer. 2001, 1: 157-162. 10.1038\/35101031","journal-title":"Nat Rev Cancer"},{"key":"482_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/BF01366952","volume":"122","author":"AG Knudson","year":"1996","unstructured":"Knudson AG: Hereditary cancer: two hits revisited. J Cancer Res Clin Oncol. 1996, 122: 135-140. 10.1007\/BF01366952","journal-title":"J Cancer Res Clin Oncol"},{"key":"482_CR3","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1073\/pnas.68.4.820","volume":"68","author":"AG Knudson Jr","year":"1971","unstructured":"Knudson AG: Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971, 68: 820-823. 10.1073\/pnas.68.4.820","journal-title":"Proc Natl Acad Sci USA"},{"key":"482_CR4","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1002\/bies.20087","volume":"26","author":"AM Soto","year":"2004","unstructured":"Soto AM, Sonnenschein C: The somatic mutation theory of cancer: growing problems with the paradigm?. Bioessays. 2004, 26: 1097-1107. 10.1002\/bies.20087","journal-title":"Bioessays"},{"key":"482_CR5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/1098-2744(200012)29:4<205::AID-MC1002>3.0.CO;2-W","volume":"29","author":"C Sonnenschein","year":"2000","unstructured":"Sonnenschein C, Soto AM: Somatic mutation theory of carcinogenesis: why it should be dropped and replaced. Mol Carcinog. 2000, 29: 205-211. 10.1002\/1098-2744(200012)29:4<205::AID-MC1002>3.0.CO;2-W","journal-title":"Mol Carcinog"},{"key":"482_CR6","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/bies.10023","volume":"24","author":"RA Veitia","year":"2002","unstructured":"Veitia RA: Exploring the etiology of haploinsufficiency. Bioessays. 2002, 24: 175-184. 10.1002\/bies.10023","journal-title":"Bioessays"},{"key":"482_CR7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s10897-006-9040-9","volume":"16","author":"S Ogino","year":"2007","unstructured":"Ogino S, Wilson RB, Gold B, Flodman P: Bayesian risk assessment in genetic testing for autosomal dominant disorders with age-dependent penetrance. J Genet Couns. 2007, 16: 29-39. 10.1007\/s10897-006-9040-9","journal-title":"J Genet Couns"},{"key":"482_CR8","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nature05316","volume":"444","author":"A Sigal","year":"2006","unstructured":"Sigal A, Milo R, Cohen A, Geva-Zatorsky N, Klein Y, Liron Y, Rosenfeld N, Danon T, Perzov N, Alon U: Variability and memory of protein levels in human cells. Nature. 2006, 444: 643-646. 10.1038\/nature05316","journal-title":"Nature"},{"key":"482_CR9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1196\/annals.1339.018","volume":"1059","author":"SA Abdulkadir","year":"2005","unstructured":"Abdulkadir SA: Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1. Ann N Y Acad Sci. 2005, 1059: 33-40. 10.1196\/annals.1339.018","journal-title":"Ann N Y Acad Sci"},{"key":"482_CR10","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S1535-6108(03)00047-3","volume":"3","author":"JA Magee","year":"2003","unstructured":"Magee JA, Abdulkadir SA, Milbrandt J: Haploinsufficiency at the Nkx3.1 locus. A paradigm for stochastic, dosage-sensitive gene regulation during tumor initiation. Cancer Cell. 2003, 3: 273-283. 10.1016\/S1535-6108(03)00047-3","journal-title":"Cancer Cell"},{"key":"482_CR11","doi-asserted-by":"publisher","first-page":"13783","DOI":"10.1073\/pnas.212386999","volume":"99","author":"R Kemkemer","year":"2002","unstructured":"Kemkemer R, Schrank S, Vogel W, Gruler H, Kaufmann D: Increased noise as an effect of haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1 in vitro. Proc Natl Acad Sci USA. 2002, 99: 13783-13788. 10.1073\/pnas.212386999","journal-title":"Proc Natl Acad Sci USA"},{"key":"482_CR12","doi-asserted-by":"publisher","first-page":"15641","DOI":"10.1073\/pnas.95.26.15641","volume":"95","author":"DL Cook","year":"1998","unstructured":"Cook DL, Gerber AN, Tapscott SJ: Modeling stochastic gene expression: implications for haploinsufficiency. Proc Natl Acad Sci USA. 1998, 95: 15641-15646. 10.1073\/pnas.95.26.15641","journal-title":"Proc Natl Acad Sci USA"},{"key":"482_CR13","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1088\/1478-3975\/3\/3\/005","volume":"3","author":"R Karmakar","year":"2006","unstructured":"Karmakar R, Bose I: Stochastic model of transcription factor-regulated gene expression. Phys Biol. 2006, 3: 200-208. 10.1088\/1478-3975\/3\/3\/005","journal-title":"Phys Biol"},{"key":"482_CR14","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1172\/JCI0215043","volume":"109","author":"JG Seidman","year":"2002","unstructured":"Seidman JG, Seidman C: Transcription factor haploinsufficiency: when half a loaf is not enough. J Clin Invest. 2002, 109: 451-455.","journal-title":"J Clin Invest"},{"key":"482_CR15","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1126\/science.1113834","volume":"310","author":"O Brandman","year":"2005","unstructured":"Brandman O, Ferrell JE, Li R, Meyer T: Interlinked fast and slow positive feedback loops drive reliable cell decisions. Science. 2005, 310: 496-498. 10.1126\/science.1113834","journal-title":"Science"},{"key":"482_CR16","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.1371\/journal.pcbi.0040008","volume":"4","author":"G Hornung","year":"2008","unstructured":"Hornung G, Barkai N: Noise propagation and signaling sensitivity in biological networks: a role for positive feedback. PLoS Comput Biol. 2008, 4: e8- 10.1371\/journal.pcbi.0040008","journal-title":"PLoS Comput Biol"},{"key":"482_CR17","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780195301069.001.0001","volume-title":"Rhythms of the brain","author":"G Buzs\u00e1ki","year":"2006","unstructured":"Buzs\u00e1ki G: Rhythms of the brain. 2006, Oxford; New York: Oxford University Press,"},{"key":"482_CR18","doi-asserted-by":"publisher","first-page":"26117","DOI":"10.1063\/1.1886386","volume":"15","author":"MA Zaks","year":"2005","unstructured":"Zaks MA, Sailer X, Schimansky-Geier L, Neiman AB: Noise induced complexity: from subthreshold oscillations to spiking in coupled excitable systems. Chaos. 2005, 15: 26117- 10.1063\/1.1886386","journal-title":"Chaos"},{"key":"482_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/9780470191651","volume-title":"Multiscale analysis of complex time series: integration of chaos and random fractal theory, and beyond","author":"J Gao","year":"2007","unstructured":"Gao J: Multiscale analysis of complex time series: integration of chaos and random fractal theory, and beyond. 2007, Hoboken, N.J.: Wiley-Interscience,"},{"key":"482_CR20","volume-title":"Nonlinear time series analysis","author":"H Kantz","year":"2004","unstructured":"Kantz H, Schreiber T: Nonlinear time series analysis. 2004, Cambridge, UK; New York: Cambridge University Press, 2,","edition":"2"},{"key":"482_CR21","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1126\/science.1105891","volume":"309","author":"JM Raser","year":"2005","unstructured":"Raser JM, O'Shea EK: Noise in gene expression: origins, consequences, and control. Science. 2005, 309: 2010-2013. 10.1126\/science.1105891","journal-title":"Science"},{"key":"482_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.pbiomolbio.2004.11.004","volume":"89","author":"B Laforge","year":"2005","unstructured":"Laforge B, Guez D, Martinez M, Kupiec JJ: Modeling embryogenesis and cancer: an approach based on an equilibrium between the autostabilization of stochastic gene expression and the interdependence of cells for proliferation. Prog Biophys Mol Biol. 2005, 89: 93-120. 10.1016\/j.pbiomolbio.2004.11.004","journal-title":"Prog Biophys Mol Biol"},{"key":"482_CR23","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/nrg1750","volume":"7","author":"AM Arias","year":"2006","unstructured":"Arias AM, Hayward P: Filtering transcriptional noise during development: concepts and mechanisms. Nat Rev Genet. 2006, 7: 34-44. 10.1038\/nrg1750","journal-title":"Nat Rev Genet"},{"key":"482_CR24","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/nature01546","volume":"422","author":"WJ Blake","year":"2003","unstructured":"Blake WJ, M KA, Cantor CR, Collins JJ: Noise in eukaryotic gene expression. Nature. 2003, 422: 633-637. 10.1038\/nature01546","journal-title":"Nature"},{"key":"482_CR25","unstructured":"https:\/\/simtk.org\/home\/bionet"},{"key":"482_CR26","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1752-0509-1-13","volume":"1","author":"WJ Bosl","year":"2007","unstructured":"Bosl WJ: Systems biology by the rules: hybrid intelligent systems for pathway modeling and discovery. BMC Syst Biol. 2007, 1: 13- 10.1186\/1752-0509-1-13","journal-title":"BMC Syst Biol"},{"key":"482_CR27","first-page":"19","volume":"18","author":"PA Gabow","year":"1989","unstructured":"Gabow PA, Schrier RW: Pathophysiology of adult polycystic kidney disease. Adv Nephrol Necker Hosp. 1989, 18: 19-32.","journal-title":"Adv Nephrol Necker Hosp"},{"key":"482_CR28","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/0092-8674(95)90339-9","volume":"81","author":"Anonymous","year":"1995","unstructured":", : Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium. Cell. 1995, 81: 289-298.","journal-title":"Cell"},{"key":"482_CR29","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/ng0695-151","volume":"10","author":"J Hughes","year":"1995","unstructured":"Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millan JL, Gamble V, Harris PC: The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet. 1995, 10: 151-160. 10.1038\/ng0695-151","journal-title":"Nat Genet"},{"key":"482_CR30","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0888-7543(11)80001-7","volume":"18","author":"WJ Kimberling","year":"1993","unstructured":"Kimberling WJ, Kumar S, Gabow PA, Kenyon JB, Connolly CJ, Somlo S: Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics. 1993, 18: 467-472.","journal-title":"Genomics"},{"key":"482_CR31","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1126\/science.272.5266.1339","volume":"272","author":"T Mochizuki","year":"1996","unstructured":"Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, et al.: PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science. 1996, 272: 1339-1342. 10.1126\/science.272.5266.1339","journal-title":"Science"},{"key":"482_CR32","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1006\/bbrc.2001.4554","volume":"282","author":"PM Vassilev","year":"2001","unstructured":"Vassilev PM, Guo L, Chen XZ, Segal Y, Peng JB, Basora N, Babakhanlou H, Cruger G, Kanazirska M, Ye C, et al.: Polycystin-2 is a novel cation channel implicated in defective intracellular Ca(2+) homeostasis in polycystic kidney disease. Biochem Biophys Res Commun. 2001, 282: 341-350. 10.1006\/bbrc.2001.4554","journal-title":"Biochem Biophys Res Commun"},{"key":"482_CR33","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1073\/pnas.98.3.1182","volume":"98","author":"S Gonzalez-Perrett","year":"2001","unstructured":"Gonzalez-Perrett S, Kim K, Ibarra C, Damiano AE, Zotta E, Batelli M, Harris PC, Reisin IL, Arnaout MA, Cantiello HF: Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel. Proc Natl Acad Sci USA. 2001, 98: 1182-1187. 10.1073\/pnas.021456598","journal-title":"Proc Natl Acad Sci USA"},{"key":"482_CR34","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0092-8674(00)81570-6","volume":"93","author":"G Wu","year":"1998","unstructured":"Wu G, D'Agati V, Cai Y, Markowitz G, Park JH, Reynolds DM, Maeda Y, Le TC, Hou H, Kucherlapati R, et al.: Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell. 1998, 93: 177-188. 10.1016\/S0092-8674(00)81570-6","journal-title":"Cell"},{"key":"482_CR35","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/S0092-8674(00)81793-6","volume":"87","author":"F Qian","year":"1996","unstructured":"Qian F, Watnick TJ, Onuchic LF, Germino GG: The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell. 1996, 87: 979-987. 10.1016\/S0092-8674(00)81793-6","journal-title":"Cell"},{"key":"482_CR36","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1172\/JCI22850","volume":"115","author":"S Nishio","year":"2005","unstructured":"Nishio S, Hatano M, Nagata M, Horie S, Koike T, Tokuhisa T, Mochizuki T: Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation. J Clin Invest. 2005, 115: 910-918.","journal-title":"J Clin Invest"},{"key":"482_CR37","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1172\/JCI119090","volume":"98","author":"L Geng","year":"1996","unstructured":"Geng L, Segal Y, Peissel B, Deng N, Pei Y, Carone F, Rennke HG, Glucksmann-Kuis AM, Schneider MC, Ericsson M, et al.: Identification and localization of polycystin, the PKD1 gene product. J Clin Invest. 1996, 98: 2674-2682. 10.1172\/JCI119090","journal-title":"J Clin Invest"},{"key":"482_CR38","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1073\/pnas.93.4.1524","volume":"93","author":"CJ Ward","year":"1996","unstructured":"Ward CJ, Turley H, Ong AC, Comley M, Biddolph S, Chetty R, Ratcliffe PJ, Gattner K, Harris PC: Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc Natl Acad Sci USA. 1996, 93: 1524-1528. 10.1073\/pnas.93.4.1524","journal-title":"Proc Natl Acad Sci USA"},{"key":"482_CR39","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1046\/j.1523-1755.1999.00659.x","volume":"56","author":"AC Ong","year":"1999","unstructured":"Ong AC, Harris PC, Davies DR, Pritchard L, Rossetti S, Biddolph S, Vaux DJ, Migone N, Ward CJ: Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2\/PKD1 cystic tissue. Kidney Int. 1999, 56: 1324-1333. 10.1046\/j.1523-1755.1999.00659.x","journal-title":"Kidney Int"},{"key":"482_CR40","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1093\/ndt\/12.6.1089","volume":"12","author":"PC Harris","year":"1997","unstructured":"Harris PC, Watson ML: Autosomal dominant polycystic kidney disease: neoplasia in disguise?. Nephrol Dial Transplant. 1997, 12: 1089-1090. 10.1093\/ndt\/12.6.1089","journal-title":"Nephrol Dial Transplant"},{"key":"482_CR41","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1038\/nm1783","volume":"14","author":"X Li","year":"2008","unstructured":"Li X, Magenheimer BS, Xia S, Johnson T, Wallace DP, Calvet JP, Li R: A tumor necrosis factor-alpha-mediated pathway promoting autosomal dominant polycystic kidney disease. Nat Med. 2008, 14: 863-868. 10.1038\/nm1783","journal-title":"Nat Med"},{"key":"482_CR42","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1056\/NEJMra002168","volume":"345","author":"SS Fajans","year":"2001","unstructured":"Fajans SS, Bell GI, Polonsky KS: Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med. 2001, 345: 971-980. 10.1056\/NEJMra002168","journal-title":"N Engl J Med"},{"key":"482_CR43","volume-title":"Basic & clinical endocrinology","author":"FS Greenspan","year":"2004","unstructured":"Greenspan FS, Gardner DG: Basic & clinical endocrinology. 2004, New York: McGraw-Hill, 7,","edition":"7"},{"key":"482_CR44","doi-asserted-by":"publisher","DOI":"10.1002\/9781444316728","volume-title":"Brook's clinical pediatric endocrinology","author":"CGD Brook","year":"2009","unstructured":"Brook CGD, Clayton PE, Brown RS: Brook's clinical pediatric endocrinology. 2009, Chichester, West Sussex, UK; Hoboken, NJ: Wiley-Blackwell, 6,","edition":"6"},{"key":"482_CR45","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/ng1097-138","volume":"17","author":"DA Stoffers","year":"1997","unstructured":"Stoffers DA, Ferrer J, Clarke WL, Habener JF: Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet. 1997, 17: 138-139. 10.1038\/ng1097-138","journal-title":"Nat Genet"},{"key":"482_CR46","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.2337\/diabetes.51.8.2355","volume":"51","author":"J Ferrer","year":"2002","unstructured":"Ferrer J: A genetic switch in pancreatic beta-cells: implications for differentiation and haploinsufficiency. Diabetes. 2002, 51: 2355-2362. 10.2337\/diabetes.51.8.2355","journal-title":"Diabetes"},{"key":"482_CR47","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.cell.2005.04.006","volume":"121","author":"WJ Bosl","year":"2005","unstructured":"Bosl WJ, Li R: Mitotic-exit control as an evolved complex system. Cell. 2005, 121: 325-333. 10.1016\/j.cell.2005.04.006","journal-title":"Cell"},{"key":"482_CR48","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.1007\/s00125-007-0833-7","volume":"50","author":"SS Fajans","year":"2007","unstructured":"Fajans SS, Bell GI: Macrosomia and neonatal hypoglycaemia in RW pedigree subjects with a mutation (Q268X) in the gene encoding hepatocyte nuclear factor 4alpha (HNF4A). Diabetologia. 2007, 50: 2600-2601. 10.1007\/s00125-007-0833-7","journal-title":"Diabetologia"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-93.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1752-0509-4-93\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-93.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T02:33:07Z","timestamp":1548210787000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-4-93"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,29]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["482"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-4-93","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,29]]},"article-number":"93"}}