High-throughput Detection Of Potentially Active L1 Elements In Human Genomes
The active human retrotransposon L1 is the most prevalent human retroelement, constituting 17% of the mass of the human genome and contributing significantly to mutagenesis. L1 mutagenizes human genomes in a number of ways including insertional mutagenesis of itself and other retrotransposons, creating of DNA double strand breaks, and induction of non-allelic homologous recombination. Through these processes, the activity of L1 is responsible for approximately 0.5% of all new genetic diseases. All L1-derived mutagenesis stems from the activity of a small number of intact full-length L1 loci that remain capable of mobilization. A smaller subset of these active L1s are called hot L1s and are responsible for the vast majority of all L1 activity. Hot L1s are polymorphic in the population and represent evolutionarily recent L1 insertion events. Here, we show that potentially active full length L1 elements are more prevalent in individual genomes than previously believed. We find that the typical individual likely harbors approximately 60 active and 50 hot L1s. However, we also find that there is significant variation between individuals in numbers of potentially active L1s. As a result, the mutagenic burden associated with L1 likely varies between individuals.