title: A large-scale zebrafish gene knockout resource for the genome-wide study of gene function.
abstract: With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way. The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation. Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome. We also report the first 6144 mutagenized and archived F1's predicted to carry up to 3776 mutations in annotated genes. Using in vitro fertilization, we have rescued and characterized ~0.5% of the predicted mutations, showing mutation efficacy and a variety of phenotypes relevant to both developmental processes and human genetic diseases. Mutagenized fish lines are being made freely available to the public through the Zebrafish International Resource Center. These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome.
authors: Developmental Genomics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Gaurav K
authors: GK
authors: Varshney
authors: Jing
authors: J
authors: Lu
authors: Derek E
authors: DE
authors: Gildea
authors: Haigen
authors: H
authors: Huang
authors: Wuhong
authors: W
authors: Pei
authors: Zhongan
authors: Z
authors: Yang
authors: Sunny C
authors: SC
authors: Huang
authors: David
authors: D
authors: Schoenfeld
authors: Nam H
authors: NH
authors: Pho
authors: David
authors: D
authors: Casero
authors: Takashi
authors: T
authors: Hirase
authors: Deborah
authors: D
authors: Mosbrook-Davis
authors: Suiyuan
authors: S
authors: Zhang
authors: Li-En
authors: LE
authors: Jao
authors: Bo
authors: B
authors: Zhang
authors: Ian G
authors: IG
authors: Woods
authors: Steven
authors: S
authors: Zimmerman
authors: Alexander F
authors: AF
authors: Schier
authors: Tyra G
authors: TG
authors: Wolfsberg
authors: Matteo
authors: M
authors: Pellegrini
authors: Shawn M
authors: SM
authors: Burgess
authors: Shuo
authors: S
authors: Lin
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods; D017988:Gammaretrovirus / Q000502:physiology; D055786:Gene Knockout Techniques; D055106:Genome-Wide Association Study; D023281:Genomics; D058977:Molecular Sequence Annotation; D016254:Mutagenesis, Insertional; D009154:Mutation; D010641:Phenotype; D016662:Virus Integration; D015027:Zebrafish / Q000235:genetics*
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