PUBLICATION

Genetic Screen for Postembryonic Development in the Zebrafish (Danio rerio): Dominant Mutations Affecting Adult Form.

Authors
Henke, K., Daane, J.M., Hawkins, M.B., Dooley, C.M., Busch-Nentwich, E.M., Stemple, D.L., Harris, M.P.
ID
ZDB-PUB-170825-12
Date
2017
Source
Genetics   207(2): 609-623 (Journal)
Registered Authors
Busch-Nentwich, Elisabeth, Dooley, Christopher, Harris, Matthew, Henke, Katrin, Stemple, Derek L.
Keywords
dominant screen, mapping, pigment, post-embryonic, skeletogenesis, zebrafish
MeSH Terms
  • Animals
  • Bone Development/genetics*
  • Genes, Dominant*
  • Haplotypes
  • Mutagenesis*
  • Phenotype
  • Skin Pigmentation/genetics*
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics
(all 10)
PubMed
28835471 Full text @ Genetics
Abstract
Large-scale forward genetic screens have been instrumental for identifying genes that regulate development, homeostasis, and regeneration, as well as the mechanisms of disease. The zebrafish, Danio rerio, is an established genetic and developmental model used in genetic screens to uncover genes necessary for early development. However, the regulation of postembryonic development has received less attention as these screens are more labor intensive and require extensive resources. The lack of systematic interrogation of late development leaves large aspects of the genetic regulation of adult form and physiology unresolved. To understand the genetic control of postembryonic development, we performed a dominant screen for phenotypes affecting the adult zebrafish. In our screen, we identified 72 adult viable mutants showing changes in the shape of the skeleton as well as defects in pigmentation. For efficient mapping of these mutants and mutation identification, we devised a new mapping strategy based on identification of mutant-specific haplotypes. Using this method in combination with a candidate gene approach, we were able to identify linked mutations for 22 out of 25 mutants analyzed. Broadly, our mutational analysis suggests that there are key genes and pathways associated with late development. Many of these pathways are shared with humans and are affected in various disease conditions, suggesting constraint in the genetic pathways that can lead to change in adult form. Taken together, these results show that dominant screens are a feasible and productive means to identify mutations that can further our understanding of gene function during postembryonic development and in disease.
Genes / Markers
Marker Marker Type Name
cmnGENEcalymmin
col1a1aGENEcollagen, type I, alpha 1a
col1a1bGENEcollagen, type I, alpha 1b
col1a2GENEcollagen, type I, alpha 2
col2a1aGENEcollagen, type II, alpha 1a
dll4GENEdelta-like 4 (Drosophila)
edarGENEectodysplasin A receptor
gja1bGENEgap junction protein alpha 1b
gja5bGENEgap junction protein, alpha 5b
itpr3GENEinositol 1,4,5-trisphosphate receptor, type 3
1 - 10 of 18
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Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
dmh1
    Point Mutation
    dmh3
      Point Mutation
      dmh4
        Point Mutation
        dmh7
          Point Mutation
          dmh8
            Point Mutation
            dmh9
              Point Mutation
              dmh11
                Unknown
                dmh13
                  Point Mutation
                  dmh14
                    Point Mutation
                    dmh15
                      Point Mutation
                      1 - 10 of 25
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                      Human Disease / Model
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      Antibodies
                      Orthology
                      Engineered Foreign Genes
                      No data available
                      Mapping