A method for calculating probabilities of fitness consequences for point mutations across the human genome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03

AUTHORS

Brad Gulko, Melissa J Hubisz, Ilan Gronau, Adam Siepel

ABSTRACT

We describe a new computational method for estimating the probability that a point mutation at each position in a genome will influence fitness. These 'fitness consequence' (fitCons) scores serve as evolution-based measures of potential genomic function. Our approach is to cluster genomic positions into groups exhibiting distinct 'fingerprints' on the basis of high-throughput functional genomic data, then to estimate a probability of fitness consequences for each group from associated patterns of genetic polymorphism and divergence. We have generated fitCons scores for three human cell types on the basis of public data from ENCODE. In comparison with conventional conservation scores, fitCons scores show considerably improved prediction power for cis regulatory elements. In addition, fitCons scores indicate that 4.2-7.5% of nucleotides in the human genome have influenced fitness since the human-chimpanzee divergence, and they suggest that recent evolutionary turnover has had limited impact on the functional content of the genome. More... »

PAGES

276-283

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3196

    DOI

    http://dx.doi.org/10.1038/ng.3196

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1034264039

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25599402


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