PUBLICATION

Rapid identification of kidney cyst mutations by whole exome sequencing in zebrafish

Authors
Ryan, S., Willer, J., Marjoram, L., Bagwell, J., Mankiewicz, J., Leshchiner, I., Goessling, W., Bagnat, M., and Katsanis, N.
ID
ZDB-PUB-131119-2
Date
2013
Source
Development (Cambridge, England)   140(21): 4445-4451 (Journal)
Registered Authors
Bagnat, Michel, Goessling, Wolfram, Katsanis, Nicholas, Willer, Jason
Keywords
kidney cyst, exome sequencing, cilia
MeSH Terms
  • Animals
  • Cysts/genetics*
  • DNA Mutational Analysis/methods*
  • Exome/genetics*
  • Genetic Linkage
  • Kidney/pathology*
  • Microscopy, Confocal
  • Mutagenesis/genetics*
  • Oligonucleotides/genetics
  • Zebrafish/genetics*
PubMed
24130329 Full text @ Development
Abstract

Forward genetic approaches in zebrafish have provided invaluable information about developmental processes. However, the relative difficulty of mapping and isolating mutations has limited the number of new genetic screens. Recent improvements in the annotation of the zebrafish genome coupled to a reduction in sequencing costs prompted the development of whole genome and RNA sequencing approaches for gene discovery. Here we describe a whole exome sequencing (WES) approach that allows rapid and cost-effective identification of mutations. We used our WES methodology to isolate four mutations that cause kidney cysts; we identified novel alleles in two ciliary genes as well as two novel mutants. The WES approach described here does not require specialized infrastructure or training and is therefore widely accessible. This methodology should thus help facilitate genetic screens and expedite the identification of mutants that can inform basic biological processes and the causality of genetic disorders in humans.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping