NEW YORK (GenomeWeb News) – A new study characterizing human-specific long interspersed element-1, or LINE-1, family retrotransposon insertion sites in the human genome is hinting at a previously unappreciated role for these polymorphisms in human genetic diversity.
In a paper appearing online recently in Genome Research, University of Pennsylvania geneticist Haig Kazazian and graduate student Adam Ewing used PCR and deep sequencing to examine human-specific LINE-1 (L1) insertion sites in germ cell DNA from dozens of individuals. In the process, they uncovered hundreds of insertion sites not found in the human references genome, along with extensive insertion site differences from one individual to the next.
"[T]here is much more diversity in our genome due to insertions by this family of transposons than previously thought," Kazazian said in a statement.
Transposons are stretches of DNA that can hop from one site in the genome to another. Depending on where these jumping genes land, they may contribute to diseases such as hemophilia, Duchenne muscular dystrophy or cancer.
But, the researchers explained, transposons — and, in particular, retrotransposons, which move about the genome through the reverse transcription of RNA to DNA sequences — may also be an important source of genetic diversity.
"Retrotransposon insertion polymorphisms (RIPs) are an often-overlooked source of inter- and intra-individual genomic variation that, like other genomic variants such as SNPs and CNVs, can influence phenotype and predisposition to disease," Ewing and Kazazian wrote.
For the current paper, the researchers focused on the L1 retrotransposons, which make up roughly 17 percent of the human genome.
To assess the human-specific L1 insertions sites, they first amplified these sites from the egg or sperm cell DNA of 25 individuals (including 15 unrelated individuals) using hemi-specific nested PCR, followed by sequencing with the Illumina Genome Analyzer.
On average, the pair found 628 insertions also present in the reference genome, as well as another 152 non-reference insertions, per individual. The non-reference insertion sites appeared to be evenly dispersed across the genome, though proportionally more non-reference than reference insertions fell in inter-genic regions.
Overall, the duo identified 369 reference and non-reference insertions — 129 within intronic regions of the genome and 240 in inter-genic regions — that turned up in all of the individuals tested.
On average, though, they also detected an average of 285 insertion site differences between individuals.
From the data available so far, Ewing and Kazazian estimated that there are likely between around 3,000 and 10,000 human-specific L1 polymorphisms in the human population.
And while they noted that more research is needed to characterize the prevalence of L1 insertions in somatic cells, the researchers hope that the new study will facilitate an improved understanding of how such jumping genes contribute to human health and disease. For instance, Kazazian and his co-workers reportedly plan to embark on studies using retrotransposon genetic markers for disease association studies.