Identification of the distribution of human endogenous retroviruses K (HML-2) by PCR-based target enrichment sequencing

Background: Human endogenous retroviruses (HERVs), suspected to be transposition-defective, may reshape the transcriptional network of the human genome by regulatory elements distributed in their long terminal repeats (LTRs). HERV-K (HML-2), the most preserved group with the least number of accumulated of mutations, has been associated with aberrant gene expression in tumorigenesis and autoimmune diseases. Because of the high sequence similarity between different HERV-Ks, current methods have limitations in providing genome-wide mapping specific for individual HERV-K (HML-2) members, a major barrier in delineating HERV-K (HML-2) function. Results: In an attempt to obtain detailed distribution information of HERV-K (HML-2), we utilized a PCR-based target enrichment sequencing protocol for HERV-K (HML-2) (PTESHK) loci, which not only maps the presence of reference loci, but also identifies non-reference loci, enabling determination of the genome-wide distribution of HERV-K (HML-2) loci. Here we report on the genomic data obtained from three individuals. We identified a total of 978 loci using this method, including 30 new reference loci and 5 non-reference loci. Among the 3 individuals in our study, 14 polymorphic HERV-K (HML-2) loci were identified, and solo-LTR330 and N6p21.32 were identified as polymorphic for the first time. Conclusions: Interestingly, PTESHK provides an approach for the identification of the genome-wide distribution of HERV-K (HML-2) and can be used for the identification of polymorphic loci. Since polymorphic HERV-K (HML-2) integrations are suspected to be related to various diseases, PTESHK can supplement other emerging techniques in accessing polymorphic HERV-K (HML-2) elements in cancer and autoimmune diseases.