Summary:
Background: Human endogenous retroviruses (HERVs) seize a notable fraction of
the genome (more than 8%) and influence cellular function with both beneficial
and pernicious consequences. They originate from ancient retroviral families that
infected the germline cells millions of years ago and as a result, they are inherited in
a Mendelian fashion. They have been linked to a number of diseases such as cancer,
various autoimmune diseases, psychiatric disorders, and a number of benefits to
their “carriers”, such as strong immunity to viral infections. Some HERV insertions
are detected as solitary long terminal repeats (solo LTRs) that emerged via non-allelic
recombination events between the two identical LTRs of a full-length provirus, while
others are transcriptionally active and can affect the regulation of neighboring genes
even today. One unique feature of HERVs is that they are insertional polymorphic
elements as some of them are found only on a proportion of the human population.
The detection of these retrotransposable elements requires specialized bioinformatics analysis, especially when analyzing big data, such as those derived from Next Generation Sequencing (NGS) technology.
Results: In the present thesis, a bioinformatics tool was developed. This tool can be
used to rapidly screen, genotype, and determine the zygosity of HERV elements from
Whole Genome Sequencing (WGS) data. The tool was validated using a computationally generated pseudogenome and then it was applied to 584 individuals from the European population, whose genome was sequenced as part of the 100,000 Genome
Project (Genomics England). As a result, 40 insertional polymorphisms and 229
conserved elements of HERV-K, HERV-W, and HERV-H families were identified and
further analyzed.
Conclusions: HERVs display a wider interindividual variation than previously de-
scribed as there are characterized by high rates of heterozygosity. Our tool facilitates the detection of endogenous retroviral elements in a wide variety of organisms and should contribute to the ongoing efforts for the deciphering of their role in the etiology and progression of various diseases, immunity-acquisition for various pathogens, and genome evolution.
Keywords:
Transposable elements, Endogenous Retrovirus, HERV-K, HERV-W, HERV-H, Zygosity, Genotyping
