TRANSCRIPTOME 2002: From Functional Genomics to Systems Biology
March 10-13, 2002
Seattle, Washington, USA


Characterization of the Upstream Regions of 836 Orthologous Human/Mouse Genes

Mihaela Zavolan1, Terry Gaasterland1, and Nikolaus Rajewsky2, 1Laboratory for Computational Genomics, The Rockefeller University, New York, NY, 2Center for Studies in Physics and Biology, The Rockefeller University, New York, NY

In recent years, it has been become evident that cross species comparisons are a very powerful tool for discovering functional regions in genomic DNA [1-4]. For example, regulatory elements such as binding sites for transcription factors are frequently found in conserved parts of upstream sequences. In order to study the conservation of upstream sequences on a genome--wide level, we have developed a fully automated computational pipeline to identify pairs of orthologous genes, to unambiguously map them to the corresponding genomic sequences, to isolate their upstream regions, and to identify conserved sequence elements. Starting with the RefSeqdatabase [5] of mouse and human protein sequences, this pipeline extracted data for 836 pairs of orthologous human/mouse genes. We present the analysis of the sequence composition, degree of conservation, and presence of regulatory motifs in the upstream region of these genes.

[1] R. C. Hardison, J. Oeltjen, and W. Miller, Long Human—Mouse Sequence Alignments Reveal Novel Regulatory Elements: A Reason to Sequence the Mouse Genome, Genome Research 7:959-966 (1997).

[2] N. Jareborg, E. Birney, and R. Durbin,  Comparative Analysis of Noncoding Regions of 77 Orthologous Mouse and Human Gene Pairs, Genome Research  9:815-824 (1999).

[3] W.W. Wasserman, M.Palumbo, W. Thompson, J.W. Fickett, C.E. Lawrence, Human-mouse genome comparisons to locate regulatory sites, Nature Genetics  26:225-228 (2000).

[4] G.G.Loots, R.M. Locksley, C.M. Blankespoor, Z.E. Wang, W. Miller, E.M. Rubin, K.A.Frazer, Identification of a Coordinate Regulator of Interleukin 4, 13, and 5 by Cross--Species Sequence Comparisons, Science 288:136-140 (2000).

[5] K.D. Pruitt and D.R. Maglott,  RefSeq and LocusLink: NCBI gene-centered resources  Nucleic Acids Research  29:137-140 (2001).

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