Abstract
BackgroundHuman 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.ResultsIn 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.ConclusionsInterestingly, 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.
Highlights
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)
In addition to the reference loci found in the GRCh37 genome [17], dozens of non-reference loci have been identified from whole genome sequencing (WGS) data using different analytic tools [19,20,21]
Evaluation of PCRbased target enrichment sequencing of HERV-K (PTESHK) First, we evaluated the ability of PTESHK to identify HERV-K (HML-2) loci by calculating the detection of fixed HERV-K (HML-2) loci in Chinese individuals
Summary
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. One mechanism is the viral proteins produced by HERV-K (HML-2); for example, rec, np, and env, may work as onco-proteins Another important mechanism is the regulatory functions of LTRs, which may enable the LTRs to serve as genome-wide regulators, including alternative promoters, enhancers, polyadenylation signals, and binding sites for transcription factors [10]. Polymorphic HERV-K (HML-2) integrations have the capacity to alter the expression of viral proteins as well as LTR regulation of host-genes. Studies on the genome-wide distribution of HERV-K (HML-2) to identify polymorphic insertion loci should enable the possible identification of disease-related genes and their regulation by HERV-K (HML-2) elements
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