Sequencing, identification and mapping of primed L1 elements (SIMPLE) reveals significant variation in full length L1 elements between individuals.

Vincent A Streva,Mark A Batzer,Sara Linker,Vallmer E Jordan,Dale J Hedges,Prescott L Deininger

doi:10.1186/s12864-015-1374-y

Abstract

BackgroundThere are over a half a million copies of L1 retroelements in the human genome which are responsible for as much as 0.5% of new human genetic diseases. Most new L1 inserts arise from young source elements that are polymorphic in the human genome. Highly active polymorphic “hot” L1 source elements have been shown to be capable of extremely high levels of mobilization and result in numerous instances of disease. Additionally, hot polymorphic L1s have been described to be highly active within numerous cancer genomes. These hot L1s result in mutagenesis by insertion of new L1 copies elsewhere in the genome, but also have been shown to generate additional full length L1 insertions which are also hot and able to further retrotranspose. Through this mechanism, hot L1s may amplify within a tumor and result in a continued cycle of mutagenesis.Results and conclusionsWe have developed a method to detect full-length, polymorphic L1 elements using a targeted next generation sequencing approach, Sequencing Identification and Mapping of Primed L1 Elements (SIMPLE). SIMPLE has 94% sensitivity and detects nearly all full-length L1 elements in a genome. SIMPLE will allow researchers to identify hot mutagenic full-length L1s as potential drivers of genome instability. Using SIMPLE we find that the typical individual has approximately 100 non-reference, polymorphic L1 elements in their genome. These elements are at relatively low population frequencies relative to previously identified polymorphic L1 elements and demonstrate the tremendous diversity in potentially active L1 elements in the human population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1374-y) contains supplementary material, which is available to authorized users.

Highlights

There are over a half a million copies of L1 retroelements in the human genome which are responsible for as much as 0.5% of new human genetic diseases
Restriction sites located at different lengths away from the element will amplify with differential efficiencies, as will different arbitrary primers
Allele frequency estimates of novel full length L1s Because our study identified numerous novel full-length L1s that we anticipate are present at low allele frequency based on their frequency within our seven-individual population (Additional file 7: Figure S3), we wanted to determine the allele frequencies of the polymorphic full length L1 elements detected in our study in a larger population of individuals

Summary

Introduction

There are over a half a million copies of L1 retroelements in the human genome which are responsible for as much as 0.5% of new human genetic diseases. Most new L1 inserts arise from young source elements that are polymorphic in the human genome. Active polymorphic “hot” L1 source elements have been shown to be capable of extremely high levels of mobilization and result in numerous instances of disease. Hot polymorphic L1s have been described to be highly active within numerous cancer genomes These hot L1s result in mutagenesis by insertion of new L1 copies elsewhere in the genome, and have been shown to generate additional full length L1 insertions which are hot and able to further retrotranspose. It is not surprising that studies have shown the elements most likely to be active are those that have most recently inserted and may not have become fixed in the population [11,12,13]

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