title: Sequencing, identification and mapping of primed L1 elements (SIMPLE) reveals significant variation in full length L1 elements between individuals.
abstract: 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.
  
  
  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.
authors.affiliation: Tulane Cancer Center and Department of Epidemiology, Tulane University, New Orleans, LA, USA. vincent.streva@childrens.harvard.edu.|Present Address: Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. vincent.streva@childrens.harvard.edu.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Streva
authors.affiliation: Department of Biology, Louisiana State University, Baton Rouge, LA, USA. vjorda7@lsu.edu.
authors.forename: Vallmer E
authors.initials: VE
authors.lastname: Jordan
authors.affiliation: Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA. slinker@salk.edu.
authors.forename: Sara
authors.initials: S
authors.lastname: Linker
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. Dale.Hedges@osumc.edu.
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Hedges
authors.affiliation: Department of Biology, Louisiana State University, Baton Rouge, LA, USA. mbatzer@lsu.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Batzer
authors.affiliation: Tulane Cancer Center and Department of Epidemiology, Tulane University, New Orleans, LA, USA. pdeinin@tulane.edu.
authors.forename: Prescott L
authors.initials: PL
authors.lastname: Deininger
mesh_terms: D000483:Alleles; D002460:Cell Line; D002874:Chromosome Mapping; D005347:Fibroblasts / Q000378:metabolism; D005787:Gene Frequency; D056726:Genetic Association Studies; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*