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Comparative analyses of multi-species sequences from targeted genomic regions


The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding1,2,3,4,5,6 and conserved non-coding4,6,7 regions, including regulatory elements8,9,10, and provide insight into the forces that have rendered modern-day genomes6. As a complement to whole-genome sequencing efforts3,5,6, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

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Figure 1: Patterns of sequence conservation.
Figure 2: Detection of MCSs by using different mammalian sequences.
Figure 3: Comparison of genome dynamics among species.


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We thank J. Weissenbach and H. Roest Crollius for Tetraodon BACs; M. Diekhans for computational expertise; N. Goldman and Z. Yang for advice on phylogenetic analyses; and F. Collins and J. Mullikin for critically reading the manuscript. We acknowledge the support of the National Human Genome Research Institute (National Institutes of Health) and the Howard Hughes Medical Institute.

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Correspondence to E. D. Green.

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Thomas, J., Touchman, J., Blakesley, R. et al. Comparative analyses of multi-species sequences from targeted genomic regions. Nature 424, 788–793 (2003).

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