ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development
| Autor: | Fabio Sirchia, Adrian S. Woolf, Jonas Winkler, Chiea Chuen Khor, Simon Wilkins, Benjamin Odermatt, Johanna M. Schmidt, Wolfgang Rösch, Johannes Schumacher, Ekkehart Jenetzky, Öznur Yilmaz, Heiko Reutter, Christina Clementson Kockum, Michael Ludwig, Simeon A. Boyadjiev, Gillian Barker, David Keene, Federico Martinón-Torres, Anne K. Ebert, Jia Cao, Daiki Kajioka, William G. Newman, Rong Zhang, Sandra Barth, Jörg Ellinger, Nadine Zwink, Michael Knapp, John P. Gearhart, Michael Pleschka, Carlo Marcelis, Glenda M. Beaman, Stefanie Heilmann-Heimbach, Kentaro Suzuki, Gen Yamada, Agneta Nordenskjöld, Wout F.J. Feitz, Alfredo Brusco, Gundela Holmdahl, Raimondo M. Cervellione, Wei Cheng, Massimo Di Grazia, Martin L. Hibberd |
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| Přispěvatelé: | Zhang, Rong, Knapp, Michael, Suzuki, Kentaro, Kajioka, Daiki, Schmidt, Johanna M., Winkler, Jona, Yilmaz, Öznur, Pleschka, Michael, Cao, Jia, Kockum, Christina Clementson, Barker, Gillian, Holmdahl, Gundela, Beaman, Glenda, Keene, David, Woolf, Adrian S., Cervellione, Raimondo M., Cheng, Wei, Wilkins, Simon, Gearhart, John P., Sirchia, Fabio, DI GRAZIA, Massimo, Ebert, Anne Karolin, Rösch, Wolfgang, Ellinger, Jörg, Jenetzky, Ekkehart, Zwink, Nadine, Feitz, Wout F., Marcelis, Carlo, Schumacher, Johanne, Martinón Torres, Federico, Hibberd, Martin Lloyd, Khor, Chiea Chuen, Heilmann Heimbach, Stefanie, Barth, Sandra, Boyadjiev, Simeon A., Brusco, Alfredo, Ludwig, Michael, Newman, William, Nordenskjöld, Agneta, Yamada, Gen, Odermatt, Benjamin, Reutter, Heiko |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Pathology Mesenchyme Urinary system Organogenesis LIM-Homeodomain Proteins Locus (genetics) 030105 genetics & heredity Biology Polymorphism Single Nucleotide bladder extrophy Article Pronephros Mesoderm 03 medical and health sciences Mice BEEC bladder extrophy urinary tract development ISL1 Genotype medicine Animals Humans Protein Isoforms Genetic Predisposition to Disease BEEC Urinary Tract Gene Zebrafish Genetics Multidisciplinary Bladder Exstrophy Gene Expression Regulation Developmental ISL1 medicine.disease Embryo Mammalian urinary tract development Bladder exstrophy 030104 developmental biology medicine.anatomical_structure Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] Larva Medical genetics Female Transcription Factors Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] |
| Zdroj: | Scientific Reports, 7 Scientific Reports Woolf, A S & Newman, W 2017, ' ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development. ', Scientific Reports . https://doi.org/10.1038/srep42170 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep42170 |
| Popis: | Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10−08). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 × 10−19. Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development. |
| Databáze: | OpenAIRE |
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