Prioritizing regions of candidate genes for efficient mutation screening

Terry A. Braun, Suma Shankar, Steve Davis, Brian O'Leary, Todd E. Scheetz, Abbot F. Clark, Val C. Sheffield, Thomas L. Casavant, Edwin M. Stone

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The availability of the complete sequence of the human genome has dramatically facilitated the search for disease-causing sequence variations. In fact, the rate-limiting step has shifted from the discovery and characterization of candidate genes to the actual screening of human populations and the subsequent interpretation of observed variations. In this study we tested the hypothesis that some segments of candidate genes are more likely than others to contain disease-causing variations and that these segments can be predicted bioinformatically. A bioinformatic technique, prioritization of annotated regions (PAR), was developed to predict the likelihood that a specific coding region of a gene will harbor a disease-causing mutation based on conserved protein functional domains and protein secondary structures. This method was evaluated by using it to analyze 710 genes that collectively harbor 4,498 previously identified mutations. Nearly 50% of the genes were recognized as disease-associated after screening only 9% of the complete coding sequence. The PAR technique identified 90% of the genes as containing at least one mutation, with less than 40% of the screening resources that traditional approaches would require. These results suggest that prioritization strategies such as PAR can accelerate disease-gene identification through more efficient use of screening resources.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalHuman Mutation
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Keywords

  • Candidate prioritization
  • Disease-gene identification
  • Mutation screening

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Prioritizing regions of candidate genes for efficient mutation screening'. Together they form a unique fingerprint.

  • Cite this

    Braun, T. A., Shankar, S., Davis, S., O'Leary, B., Scheetz, T. E., Clark, A. F., Sheffield, V. C., Casavant, T. L., & Stone, E. M. (2006). Prioritizing regions of candidate genes for efficient mutation screening. Human Mutation, 27(2), 195-200. https://doi.org/10.1002/humu.20247