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ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development
- Source :
- 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
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
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.
- Subjects :
- 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]
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....338fd36582bd0300a7b5ab3f8f28de1d
- Full Text :
- https://doi.org/10.1038/srep42170