Gene selection tool (GST): A R-based tool for genetic disorders based on the sliding-window proportion test using whole-exome sequencing data

PLoS One. 2017 Sep 28;12(9):e0185514. doi: 10.1371/journal.pone.0185514. eCollection 2017.

Abstract

Whole-exome sequencing (WES) can identify causative mutations in hereditary diseases. However, WES data might have a large candidate variant list, including false positives. Moreover, in families, it is more difficult to select disease-associated variants because many variants are shared among members. To reduce false positives and extract accurate candidates, we used a multilocus variant instead of a single-locus variant (SNV). We set up a specific window to analyze the multilocus variant and devised a sliding-window approach to observe all variants. We developed the gene selection tool (GST) based on proportion tests for linkage analysis using WES data. This tool is R program coded and has high sensitivity. We tested our code to find the gene for hereditary spastic paraplegia using SNVs from a specific family and identified the gene known to cause the disease in a significant gene list. The list identified other genes that might be associated with the disease.

MeSH terms

  • Chromosomes, Human, X / genetics
  • Chromosomes, Human, Y / genetics
  • Computer Simulation
  • Exome / genetics*
  • Female
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Male
  • Pedigree
  • Sequence Analysis, DNA / methods*
  • Software*

Grants and funding

This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2014M3C9A2064618 to DK), and by the KRIBB Research Initiative Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.