Functional characterization of the zebrafish genes requires accurate knowledge of the gene structure and gene expression. In proposal we combine high-throughput sequencing techniques (Ribosome profile and RNA-seq) and bioinformatics to improve the current annotation of coding and non-coding genes, by determining the translation start and stop sites in each coding gene (Aim 2), define the transcription start site, 5'and 3'UTRs (Aim 1), annotate putative alternatively spliced exons in the zebrafish genes (Aim 1), and develop a gene expression atlas during embryogenesis and organogenesis (Aim 1) The experiments outlined in this proposal have the ultimate goal of improving functional genomics in zebrafish and will provide two fundamental tools to the community: i) improved annotation of the zebrafish genes including coding potential, translation start site and transcript structure and ii) community defined, open access zebrafish expression atlas across embryonic/ larval stages and organogenesis. In the future, the results derived from this project will facilitate the functional characterization of the zebrafish genes and will establsh a frame work to understand the structure and the function of vertebrate genes.

Public Health Relevance

The genome of vertebrate animals is very similar to that of humans. By studying the secrets underlying in the genetic code of the vertebrate model system zebrafish, we aim to characterize the elements of the genome to provide better tools to zebrafish researchers to understand vertebrate development and human disease. The experiments outlined in this proposal will also help us uncover novel genes unknown in humans providing important insights about the building blocks that are used in humans to undertake different functions in the cell.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD074078-02
Application #
8530259
Study Section
Special Emphasis Panel (ZRG1-CB-Z (56))
Program Officer
Coulombe, James N
Project Start
2012-08-15
Project End
2017-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$487,252
Indirect Cost
$181,635
Name
Yale University
Department
Genetics
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Hoffman, Ellen J; Turner, Katherine J; Fernandez, Joseph M et al. (2016) Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2. Neuron 89:725-33
Johnstone, Timothy G; Bazzini, Ariel A; Giraldez, Antonio J (2016) Upstream ORFs are prevalent translational repressors in vertebrates. EMBO J 35:706-23
Pignatelli, Miguel; Vilella, Albert J; Muffato, Matthieu et al. (2016) ncRNA orthologies in the vertebrate lineage. Database (Oxford) 2016:
Yates, Andrew; Akanni, Wasiu; Amode, M Ridwan et al. (2016) Ensembl 2016. Nucleic Acids Res 44:D710-6
Cunningham, Fiona; Amode, M Ridwan; Barrell, Daniel et al. (2015) Ensembl 2015. Nucleic Acids Res 43:D662-9
Cunningham, Fiona; Moore, Barry; Ruiz-Schultz, Nicole et al. (2015) Improving the Sequence Ontology terminology for genomic variant annotation. J Biomed Semantics 6:32
Moreno-Mateos, Miguel A; Vejnar, Charles E; Beaudoin, Jean-Denis et al. (2015) CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nat Methods 12:982-8
Yartseva, Valeria; Giraldez, Antonio J (2015) The Maternal-to-Zygotic Transition During Vertebrate Development: A Model for Reprogramming. Curr Top Dev Biol 113:191-232
Flicek, Paul; Amode, M Ridwan; Barrell, Daniel et al. (2014) Ensembl 2014. Nucleic Acids Res 42:D749-55
Lee, Mihye; Choi, Yeon; Kim, Kijun et al. (2014) Adenylation of maternally inherited microRNAs by Wispy. Mol Cell 56:696-707

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