Sequencing, identification and mapping of primed L1 elements (SIMPLE) reveals significant variation in full length L1 elements between individuals
| Autor: | Vallmer E Jordan, Mark A. Batzer, Dale J. Hedges, Vincent A Streva, Prescott L. Deininger, Sara Linker |
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| Jazyk: | angličtina |
| Předmět: |
Genome instability
Population Retrotransposon Computational biology Biology Proteomics Genome DNA sequencing Cell Line 03 medical and health sciences 0302 clinical medicine Gene Frequency Genetics Humans Polymorphism education Alleles Genetic Association Studies 030304 developmental biology 0303 health sciences education.field_of_study Polymorphism Genetic High-throughput sequencing Genome Human Methodology Article Chromosome Mapping High-Throughput Nucleotide Sequencing Sequence Analysis DNA Fibroblasts LINE1 3. Good health Long Interspersed Nucleotide Elements Human genome DNA microarray 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | BMC Genomics |
| ISSN: | 1471-2164 |
| DOI: | 10.1186/s12864-015-1374-y |
| Popis: | Background 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. 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 conclusions We 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 material The online version of this article (doi:10.1186/s12864-015-1374-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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