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

Abstract

BackgroundWhile 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.ResultsHere 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.ConclusionsBy enabling detection of polymorphic transductions, TIGER makes this form of relevant structural variation amenable for population and personal genome analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2670-x) contains supplementary material, which is available to authorized users.

Diseases of the nERVous system: retrotransposon activity in neurodegenerative disease

“…None of these studies have yet shown clear evidence for de novo insertions, or “hopping,” of the retrotransposons in decedent patient tissues or laboratory models, though it is possible that improved methods for identifying somatic de novo insertions may shed more light on this possibility. As sequencing technologies improve with longer reads [142–147], better protocols for transposon insertion profiling [146–151], and better computational tools to handle repetitive genomic regions [148–152], it may be easier to detect retrotransposon products ranging from specific loci generating elevated retrotransposon transcripts to polymorphic and de novo genome insertions.…”

Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene

“…The rarity of LINE-1-mediated pathogenic insertions described in the literature and in variant databases is attributable mostly to their low activity throughout the genome and to the technical difficulties in their detection (especially the full-length insertions). With massive parallel sequencing technology, there are also considerable limitations, particularly through short reads sequencing, and here, tailored bioinformatics analysis tools and strategies are required [ 22 ]. In the case of intronic LINE-1 insertions, detection may be hampered by the intron’s length and the fact that it mainly affects transcriptional events (e.g., intronic retentions or exonization events).…”