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Nat Rev Genet. 2008 Apr;9(4):303-13. doi: 10.1038/nrg2185.

Approaches to comparative sequence analysis: towards a functional view of vertebrate genomes.

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  • 1Genome Technology Branch, Genome Informatics Section, National Human Genome Research Institute, National Institutes of Health, 5625 Fishers Lane, Room 5N-01N, MSC9400, Bethesda, Maryland 20892, USA.


The comparison of genomic sequences is now a common approach to identifying and characterizing functional regions in vertebrate genomes. However, for theoretical reasons and because of practical issues, the generation of these data sets is non-trivial and can have many pitfalls. We are currently seeing an explosion of comparative sequence data, the benefits and limitations of which need to be disseminated to the scientific community. This Review provides a critical overview of the different types of sequence data that are available for analysis and of contemporary comparative sequence analysis methods, highlighting both their strengths and limitations. Approaches to determining the biological significance of constrained sequence are also explored.

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