Large-scale mapping of mutations affecting zebrafish development.
BACKGROUND
Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers.


RESULTS
We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM.


CONCLUSIONS
By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations.
Geisler
Robert
R
Department 3--Genetics, Max-Planck-Institut für Entwicklungsbiologie, Spemannstr, 35/III, 72076 Tübingen, Germany. robert.geisler@tuebingen.mpg.de
Rauch
Gerd-Jörg
GJ
Geiger-Rudolph
Silke
S
Albrecht
Andrea
A
van Bebber
Frauke
F
Berger
Andrea
A
Busch-Nentwich
Elisabeth
E
Dahm
Ralf
R
Dekens
Marcus P S
MP
Dooley
Christopher
C
Elli
Alexandra F
AF
Gehring
Ines
I
Geiger
Horst
H
Geisler
Maria
M
Glaser
Stefanie
S
Holley
Scott
S
Huber
Matthias
M
Kerr
Andy
A
Kirn
Anette
A
Knirsch
Martina
M
Konantz
Martina
M
Küchler
Axel M
AM
Maderspacher
Florian
F
Neuhauss
Stephan C
SC
Nicolson
Teresa
T
Ober
Elke A
EA
Praeg
Elke
E
Ray
Russell
R
Rentzsch
Brit
B
Rick
Jens M
JM
Rief
Eva
E
Schauerte
Heike E
HE
Schepp
Carsten P
CP
Schönberger
Ulrike
U
Schonthaler
Helia B
HB
Seiler
Christoph
C
Sidi
Samuel
S
Söllner
Christian
C
Wehner
Anja
A
Weiler
Christian
C
Nüsslein-Volhard
Christiane
C
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D016678:Genome; D008297:Male; D018895:Microsatellite Repeats; D016296:Mutagenesis; D009154:Mutation; D010641:Phenotype; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*