Next-generation Sequencing-based Detection of Germline L1-mediated Transductions

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2016 May 11

PMID 27161561

Citations 4

Authors

Jelena Tica

Eunjung Lee

Andreas Untergasser

Sascha Meiers

David A Garfield

Omer Gokcumen

Eileen E M Furlong

Peter J Park

Adrian M Stutz

Jan O Korbel

Affiliations

Soon will be listed here.

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.

Citing Articles

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Bae J, Lee K, Islam M, Yim H, Park H, Rho M BMC Genomics. 2018; 19(1):944.

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L1 retrotransposition in the soma: a field jumping ahead.

Faulkner G, Billon V Mob DNA. 2018; 9:22.

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

Goncalves A, Oliveira J, Coelho T, Taipa R, Melo-Pires M, Sousa M Genes (Basel). 2017; 8(10).

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References

Chaisson M, Huddleston J, Dennis M, Sudmant P, Malig M, Hormozdiari F . Resolving the complexity of the human genome using single-molecule sequencing. Nature. 2014; 517(7536):608-11. PMC: 4317254. DOI: 10.1038/nature13907. View

Evrony G, Lee E, Mehta B, Benjamini Y, Johnson R, Cai X . Cell lineage analysis in human brain using endogenous retroelements. Neuron. 2015; 85(1):49-59. PMC: 4299461. DOI: 10.1016/j.neuron.2014.12.028. View

Gilly A, Etcheverry M, Madoui M, Guy J, Quadrana L, Alberti A . TE-Tracker: systematic identification of transposition events through whole-genome resequencing. BMC Bioinformatics. 2014; 15:377. PMC: 4279814. DOI: 10.1186/s12859-014-0377-z. View

Paterson A, Weaver J, Eldridge M, Tavare S, Fitzgerald R, Edwards P . Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired-end sequencing analysis. BMC Genomics. 2015; 16:473. PMC: 4498532. DOI: 10.1186/s12864-015-1685-z. View

Pendleton M, Sebra R, Pang A, Ummat A, Franzen O, Rausch T . Assembly and diploid architecture of an individual human genome via single-molecule technologies. Nat Methods. 2015; 12(8):780-6. PMC: 4646949. DOI: 10.1038/nmeth.3454. View

Goodier J, Ostertag E, Kazazian Jr H . Transduction of 3'-flanking sequences is common in L1 retrotransposition. Hum Mol Genet. 2000; 9(4):653-7. DOI: 10.1093/hmg/9.4.653. View

Pickeral O, Makalowski W, Boguski M, Boeke J . Frequent human genomic DNA transduction driven by LINE-1 retrotransposition. Genome Res. 2000; 10(4):411-5. PMC: 310862. DOI: 10.1101/gr.10.4.411. View

Lander E, Linton L, Birren B, Nusbaum C, Zody M, Baldwin J . Initial sequencing and analysis of the human genome. Nature. 2001; 409(6822):860-921. DOI: 10.1038/35057062. View

Kent W . BLAT--the BLAST-like alignment tool. Genome Res. 2002; 12(4):656-64. PMC: 187518. DOI: 10.1101/gr.229202. View

10.

Symer D, Connelly C, Szak S, Caputo E, Cost G, Parmigiani G . Human l1 retrotransposition is associated with genetic instability in vivo. Cell. 2002; 110(3):327-38. DOI: 10.1016/s0092-8674(02)00839-5. View

11.

Szak S, Pickeral O, Landsman D, Boeke J . Identifying related L1 retrotransposons by analyzing 3' transduced sequences. Genome Biol. 2003; 4(5):R30. PMC: 156586. DOI: 10.1186/gb-2003-4-5-r30. View

12.

van den Hurk J, van de Pol D, Wissinger B, van Driel M, Hoefsloot L, de Wijs I . Novel types of mutation in the choroideremia ( CHM) gene: a full-length L1 insertion and an intronic mutation activating a cryptic exon. Hum Genet. 2003; 113(3):268-75. DOI: 10.1007/s00439-003-0970-0. View

13.

Ostertag E, Goodier J, Zhang Y, Kazazian Jr H . SVA elements are nonautonomous retrotransposons that cause disease in humans. Am J Hum Genet. 2003; 73(6):1444-51. PMC: 1180407. DOI: 10.1086/380207. View

14.

Kazazian Jr H . Mobile elements: drivers of genome evolution. Science. 2004; 303(5664):1626-32. DOI: 10.1126/science.1089670. View

15.

Athanikar J, Badge R, Moran J . A YY1-binding site is required for accurate human LINE-1 transcription initiation. Nucleic Acids Res. 2004; 32(13):3846-55. PMC: 506791. DOI: 10.1093/nar/gkh698. View

16.

Grimaldi G, Skowronski J, Singer M . Defining the beginning and end of KpnI family segments. EMBO J. 1984; 3(8):1753-9. PMC: 557592. DOI: 10.1002/j.1460-2075.1984.tb02042.x. View

17.

Luan D, Korman M, Jakubczak J, Eickbush T . Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell. 1993; 72(4):595-605. DOI: 10.1016/0092-8674(93)90078-5. View

18.

Holmes S, Dombroski B, Krebs C, Boehm C, Kazazian Jr H . A new retrotransposable human L1 element from the LRE2 locus on chromosome 1q produces a chimaeric insertion. Nat Genet. 1994; 7(2):143-8. DOI: 10.1038/ng0694-143. View

19.

Jurka J . Sequence patterns indicate an enzymatic involvement in integration of mammalian retroposons. Proc Natl Acad Sci U S A. 1997; 94(5):1872-7. PMC: 20010. DOI: 10.1073/pnas.94.5.1872. View

20.

Moran J, DeBerardinis R, Kazazian Jr H . Exon shuffling by L1 retrotransposition. Science. 1999; 283(5407):1530-4. DOI: 10.1126/science.283.5407.1530. View