A high throughput screen for active human transposable elements.

Abstract:

BACKGROUND:Transposable elements (TEs) are mobile genetic sequences that randomly propagate within their host's genome. This mobility has the potential to affect gene transcription and cause disease. However, TEs are technically challenging to identify, which complicates efforts to assess the impact of TE insertions on disease. Here we present a targeted sequencing protocol and computational pipeline to identify polymorphic and novel TE insertions using next-generation sequencing: TE-NGS. The method simultaneously targets the three subfamilies that are responsible for the majority of recent TE activity (L1HS, AluYa5/8, and AluYb8/9) thereby obviating the need for multiple experiments and reducing the amount of input material required. RESULTS:Here we describe the laboratory protocol and detection algorithm, and a benchmark experiment for the reference genome NA12878. We demonstrate a substantial enrichment for on-target fragments, and high sensitivity and precision to both reference and NA12878-specific insertions. We report 17 previously unreported loci for this individual which are supported by orthogonal long-read evidence, and we identify 1470 polymorphic and novel TEs in 12 additional samples that were previously undocumented in databases of insertion polymorphisms. CONCLUSIONS:We anticipate that future applications of TE-NGS alongside exome sequencing of patients with sporadic disease will reduce the number of unresolved cases, and improve estimates of the contribution of TEs to human genetic disease.

journal_name

BMC Genomics

journal_title

BMC genomics

authors

Kvikstad EM,Piazza P,Taylor JC,Lunter G

doi

10.1186/s12864-018-4485-4

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

115

issue

1

issn

1471-2164

pii

10.1186/s12864-018-4485-4

journal_volume

19

pub_type

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