Exploring the function of genetic variants in the non-coding genomic regions: approaches for identifying human regulatory variants affecting gene expression

Brief Bioinform. 2015 May;16(3):393-412. doi: 10.1093/bib/bbu018. Epub 2014 Jun 10.

Abstract

Understanding the genetic basis of human traits/diseases and the underlying mechanisms of how these traits/diseases are affected by genetic variations is critical for public health. Current genome-wide functional genomics data uncovered a large number of functional elements in the noncoding regions of human genome, providing new opportunities to study regulatory variants (RVs). RVs play important roles in transcription factor bindings, chromatin states and epigenetic modifications. Here, we systematically review an array of methods currently used to map RVs as well as the computational approaches in annotating and interpreting their regulatory effects, with emphasis on regulatory single-nucleotide polymorphism. We also briefly introduce experimental methods to validate these functional RVs.

Keywords: chromatin state; function validation; functional prediction; genetic mapping; regulatory variant; transcriptional gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Base Sequence
  • Chromosome Mapping / methods
  • Gene Expression Regulation / genetics*
  • Genetic Variation / genetics
  • Genome, Human / genetics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Molecular Sequence Data
  • Open Reading Frames / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Sequence Alignment / methods