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Local DNA topography correlates with functional noncoding regions of the human genome.

ABSTRACT: The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained-double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than did regions identified solely on the basis of nucleotide sequence. These results support the idea that the molecular shape of DNA is under selection and can identify evolutionary history.

SUBMITTER: Parker SC

PROVIDER: S-EPMC2749491 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Local DNA topography correlates with functional noncoding regions of the human genome.

Parker Stephen C J SC Hansen Loren L Abaan Hatice Ozel HO Tullius Thomas D TD Margulies Elliott H EH

Science (New York, N.Y.) 20090312 5925

The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12% of bases in t ...[more]

PMID: 19286520

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