Human and mouse genomic sequences will be aligned and annotated using the World Wide Web server PipMaker. This method of analysis easily identifies exons of orthologous genes. Furthermore, conserved noncoding regions can be visualized as high scoring segment pairs in a pip display. Thus, regulatory elements that are conserved via evolutionary pressure will also be annotated in this study. Specifically, alignments of syntenic human and mouse sequences will be computed and placed in a database for public access. Regulatory elements within aligned regions will be grouped based on the density of conserved noncoding sites. These groupings will be used as datasets to evaluate whether the use of defined thresholds for identifying important regulatory elements is more informative than the use of phylogenetic distance, which may find either too many conserved noncoding regions, or not enough. In addition to annotating genes from genomic sequence data (facilitating the elucidation of genes that contribute to human genetic disease) the purpose of this study is to map the regulatory elements for many of these genes. Thus, critical targets for experimental study will be identified. These results will be shared with researchers interested in studying regulated expression of genes within the aligned sequences. An additional outcome of this study is to provide datasets of aligned sequences to computer scientists interested in improving ab initio methods of identifying transcription factor binding sites in genomic sequences.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HG002325-02
Application #
6536491
Study Section
Genome Study Section (GNM)
Program Officer
Graham, Bettie
Project Start
2001-06-01
Project End
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
2
Fiscal Year
2002
Total Cost
$48,236
Indirect Cost
Name
Pennsylvania State University
Department
Biostatistics & Other Math Sci
Type
Schools of Engineering
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Elnitski, Laura; King, David; Hardison, Ross C (2006) Computational prediction of cis-regulatory modules from multispecies alignments using Galaxy, Table Browser, and GALA. Methods Mol Biol 338:91-103
King, David C; Taylor, James; Elnitski, Laura et al. (2005) Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences. Genome Res 15:1051-60
Piontkivska, Helen; Zhang, Yi; Green, Eric D et al. (2004) Multi-species sequence comparison reveals dynamic evolution of the elastin gene that has involved purifying selection and lineage-specific insertions/deletions. BMC Genomics 5:31
Blanchette, Mathieu; Kent, W James; Riemer, Cathy et al. (2004) Aligning multiple genomic sequences with the threaded blockset aligner. Genome Res 14:708-15
Kolbe, Diana; Taylor, James; Elnitski, Laura et al. (2004) Regulatory potential scores from genome-wide three-way alignments of human, mouse, and rat. Genome Res 14:700-7
Hardison, Ross C; Roskin, Krishna M; Yang, Shan et al. (2003) Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution. Genome Res 13:13-26
Frazer, Kelly A; Elnitski, Laura; Church, Deanna M et al. (2003) Cross-species sequence comparisons: a review of methods and available resources. Genome Res 13:1-12
Giardine, Belinda; Elnitski, Laura; Riemer, Cathy et al. (2003) GALA, a database for genomic sequence alignments and annotations. Genome Res 13:732-41
Hardison, R C; Chiaromonte, F; Kolbe, D et al. (2003) Global predictions and tests of erythroid regulatory regions. Cold Spring Harb Symp Quant Biol 68:335-44
Schwartz, Scott; Elnitski, Laura; Li, Mei et al. (2003) MultiPipMaker and supporting tools: Alignments and analysis of multiple genomic DNA sequences. Nucleic Acids Res 31:3518-24

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