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ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.


ABSTRACT: 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.

SUBMITTER: Zhang R 

PROVIDER: S-EPMC5296905 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.

Zhang Rong R   Knapp Michael M   Suzuki Kentaro K   Kajioka Daiki D   Schmidt Johanna M JM   Winkler Jonas J   Yilmaz Öznur Ö   Pleschka Michael M   Cao Jia J   Kockum Christina Clementson CC   Barker Gillian G   Holmdahl Gundela G   Beaman Glenda G   Keene David D   Woolf Adrian S AS   Cervellione Raimondo M RM   Cheng Wei W   Wilkins Simon S   Gearhart John P JP   Sirchia Fabio F   Di Grazia Massimo M   Ebert Anne-Karolin AK   Rösch Wolfgang W   Ellinger Jörg J   Jenetzky Ekkehart E   Zwink Nadine N   Feitz Wout F WF   Marcelis Carlo C   Schumacher Johannes J   Martinón-Torres Federico F   Hibberd Martin Lloyd ML   Khor Chiea Chuen CC   Heilmann-Heimbach Stefanie S   Barth Sandra S   Boyadjiev Simeon A SA   Brusco Alfredo A   Ludwig Michael M   Newman William W   Nordenskjöld Agneta A   Yamada Gen G   Odermatt Benjamin B   Reutter Heiko H  

Scientific reports 20170208


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 9  ...[more]

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