Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Probabilities of Fitness Consequences for Point Mutations Across the Human Genome

Brad Gulko, Melissa J. Hubisz, Ilan Gronau, Adam Siepel
doi: https://doi.org/10.1101/006825
Brad Gulko
Graduate Field of Computer Science, Cornell University, Ithaca, NY 14853, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melissa J. Hubisz
Department of Biological Statistics & Computational Biology, Cornell University, Ithaca, NY 14853, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ilan Gronau
Department of Biological Statistics & Computational Biology, Cornell University, Ithaca, NY 14853, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adam Siepel
Graduate Field of Computer Science, Cornell University, Ithaca, NY 14853, USADepartment of Biological Statistics & Computational Biology, Cornell University, Ithaca, NY 14853, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

We describe a novel computational method for estimating the probability that a point mutation at each position in a genome will influence fitness. These fitness consequence (fit-Cons) scores serve as evolution-based measures of potential genomic function. Our approach is to cluster genomic positions into groups exhibiting distinct “fingerprints” based on 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 based on public data from EN-CODE. Compared 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, in contrast to several recent studies, they suggest that recent evolutionary turnover has had limited impact on the functional content of the genome.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted September 11, 2014.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Probabilities of Fitness Consequences for Point Mutations Across the Human Genome
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Probabilities of Fitness Consequences for Point Mutations Across the Human Genome
Brad Gulko, Melissa J. Hubisz, Ilan Gronau, Adam Siepel
bioRxiv 006825; doi: https://doi.org/10.1101/006825
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Probabilities of Fitness Consequences for Point Mutations Across the Human Genome
Brad Gulko, Melissa J. Hubisz, Ilan Gronau, Adam Siepel
bioRxiv 006825; doi: https://doi.org/10.1101/006825

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (1545)
  • Biochemistry (2500)
  • Bioengineering (1757)
  • Bioinformatics (9729)
  • Biophysics (3929)
  • Cancer Biology (2990)
  • Cell Biology (4235)
  • Clinical Trials (135)
  • Developmental Biology (2653)
  • Ecology (4129)
  • Epidemiology (2033)
  • Evolutionary Biology (6933)
  • Genetics (5243)
  • Genomics (6532)
  • Immunology (2208)
  • Microbiology (7012)
  • Molecular Biology (2784)
  • Neuroscience (17412)
  • Paleontology (127)
  • Pathology (432)
  • Pharmacology and Toxicology (712)
  • Physiology (1068)
  • Plant Biology (2516)
  • Scientific Communication and Education (647)
  • Synthetic Biology (835)
  • Systems Biology (2699)
  • Zoology (439)