Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Pac Symp Biocomput. 2010:337-47.

Loss of post-translational modification sites in disease.

Author information

  • 1School of Informatics and Computing, Indiana University, Bloomington, IN 47408, USA.

Abstract

Understanding and predicting molecular cause of disease is one of the major challenges for biology and medicine. One particular area of interest continues to be computational analyses of disease-associated amino acid substitutions. To this end, various studies have been performed to identify molecular functions disrupted by disease-causing mutations. Here, we investigate the influence of disease-associated mutations on post-translational modifications. In particular, we study the loss of modification target sites as a consequence of disease mutation. We find that about 5% of disease-associated mutations may affect known modification sites, either partially (4%) of fully (1%), compared to about 2% of putatively neutral polymorphisms. Most of the fifteen post-translational modification types analyzed were found to be disrupted at levels higher than expected by chance. Molecular functions and physiochemical properties at sites of disease mutation were also compared to those of neutral polymorphisms involved in the process of post-translational modification site disruption. Disease-associated mutations in the neighborhood of post-translationally modified sites were found to be enriched in mutations that change polarity, charge, and hydrophobicity of the wild-type amino acids. Overall, these results further suggest that disruption of modification sites is an important but not the major cause of human genetic disease.

PMID:
19908386
[PubMed - indexed for MEDLINE]
PMCID:
PMC2813771
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for World Scientific Publishing Company Icon for PubMed Central
    Loading ...
    Write to the Help Desk