Next-generation sequencing-based detection of germline L1-mediated transductions

BMC Genomics. 2016 May 10:17:342. doi: 10.1186/s12864-016-2670-x.

Abstract

Background: While active LINE-1 (L1) elements possess the ability to mobilize flanking sequences to different genomic loci through a process termed transduction influencing genomic content and structure, an approach for detecting polymorphic germline non-reference transductions in massively-parallel sequencing data has been lacking.

Results: Here we present the computational approach TIGER (Transduction Inference in GERmline genomes), enabling the discovery of non-reference L1-mediated transductions by combining L1 discovery with detection of unique insertion sequences and detailed characterization of insertion sites. We employed TIGER to characterize polymorphic transductions in fifteen genomes from non-human primate species (chimpanzee, orangutan and rhesus macaque), as well as in a human genome. We achieved high accuracy as confirmed by PCR and two single molecule DNA sequencing techniques, and uncovered differences in relative rates of transduction between primate species.

Conclusions: By enabling detection of polymorphic transductions, TIGER makes this form of relevant structural variation amenable for population and personal genome analysis.

Keywords: Bioinformatics; Genetics; Genome; L1; NGS; Primates; Retrotransposon; Single-molecule sequencing; Transductions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Computational Biology / methods
  • Genome
  • Germ Cells / metabolism*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Long Interspersed Nucleotide Elements*
  • Macaca mulatta / genetics
  • Pan troglodytes / genetics
  • Transduction, Genetic*