Journal article
A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans
Genetics (Austin), Vol.207(1), pp.215-228
09/2017
DOI: 10.1534/genetics.117.1125
PMCID: PMC5586373
PMID: 28739660
Abstract
Renal agenesis (RA) is one of the more extreme examples of congenital anomalies of the kidney and urinary tract (CAKUT). Bilateral renal agenesis is almost invariably fatal at birth, and unilateral renal agenesis can lead to future health issues including end-stage renal disease. Genetic investigations have identified several gene variants that cause RA, including
,
, and
However, whereas compound null mutations of genes encoding α and γ retinoic acid receptors (RARs) cause RA in mice, to date there have been no reports of variants in RAR genes causing RA in humans. In this study, we carried out whole exome sequence analysis of two families showing inheritance of an RA phenotype, and in both identified a single candidate gene,
Analysis of a zebrafish
loss-of-function mutant revealed defects in the pronephric kidney just prior to death, and F0 CRISPR/Cas9 mutagenesis of
in the mouse revealed kidney agenesis phenotypes, implicating
in this disorder. GREB1L resides in a chromatin complex with RAR members, and our data implicate GREB1L as a coactivator for RARs. This study is the first to associate a component of the RAR pathway with renal agenesis in humans.
Details
- Title: Subtitle
- A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans
- Creators
- Patrick D Brophy - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242Maria Rasmussen - Department of Clinical Genetics, Aarhus University Hospital, Skejby, Denmark 8200Mrutyunjaya Parida - Department of Biology, University of Iowa, Iowa City, Iowa 52242Greg Bonde - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242Benjamin W Darbro - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242Xiaojing Hong - Department of Biology, University of Iowa, Iowa City, Iowa 52242Jason C Clarke - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242Kevin A Peterson - Genetics and Genomics, The Jackson Laboratory, Bar Harbor, Maine 04609James Denegre - Genetics and Genomics, The Jackson Laboratory, Bar Harbor, Maine 04609Michael Schneider - Medical Genetics, Carle Foundation Hospital and Physician Group, Urbana, Illinois 61801Caroline R Sussman - Department of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota 55905Lone Sunde - Department of Clinical Genetics, Aarhus University Hospital, Skejby, Denmark 8200Dorte L Lildballe - Department of Clinical Genetics, Aarhus University Hospital, Skejby, Denmark 8200Jens Michael Hertz - Department of Clinical Genetics, Odense University Hospital, Odense, Denmark 5000Robert A Cornell - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242Stephen A Murray - Genetics and Genomics, The Jackson Laboratory, Bar Harbor, Maine 04609J Robert Manak - 459 Biology Bldg., Department of Biology, University of Iowa, 129 E. Jefferson St., Iowa City, IA 52242. john-manak@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Genetics (Austin), Vol.207(1), pp.215-228
- DOI
- 10.1534/genetics.117.1125
- PMID
- 28739660
- PMCID
- PMC5586373
- NLM abbreviation
- Genetics
- ISSN
- 0016-6731
- eISSN
- 1943-2631
- Publisher
- United States
- Grant note
- UM1 OD023222 / NIH HHS RC4 DK090937 / NIDDK NIH HHS P30 DK090728 / NIDDK NIH HHS R01 DE021071 / NIDCR NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Medical Genetics and Genomics; Biology; Craniofacial Anomalies Research Center; Biochemistry and Molecular Biology; Dental Research
- Record Identifier
- 9983992100302771
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