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Published Online March 23, 2006
Science DOI: 10.1126/science.1124070

Reports

Submitted on December 19, 2005
Accepted on March 8, 2006

Conservation of RET Regulatory Function from Human to Zebrafish Without Sequence Similarity

Shannon Fisher 1*, Elizabeth A. Grice 2, Ryan M. Vinton 2, Seneca L. Bessling 2, Andrew S. McCallion 3*

1 McKusick-Nathans Institute of Genetic Medicine; Department of Cell Biology
2 McKusick-Nathans Institute of Genetic Medicine
3 McKusick-Nathans Institute of Genetic Medicine; Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* To whom correspondence should be addressed.
Shannon Fisher , E-mail: sfisher{at}jhmi.edu
Andrew S. McCallion , E-mail: amccalli{at}jhmi.edu

Evolutionary sequence conservation is an accepted criterion to identify noncoding regulatory sequences. We have used a transposon-based transgenic assay in zebrafish to evaluate noncoding sequences at the zebrafish ret locus, conserved among teleosts, and at the human RET locus, conserved among mammals. Most teleost sequences directed ret-specific reporter gene expression, with many displaying overlapping regulatory control. The majority of human RET noncoding sequences also directed ret-specific expression in zebrafish. Thus, vast amounts of functional sequence information may exist that would not be detected by sequence similarity approaches.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)