Human endogenous retroviruses (HERVs) have been classified into three different classes I, II, III. Betaretrovirus-like sequences, including HERV-K, belong to the class II and contains ten groups, termed HML1-10. It has been reported that an HML-10 sequence, termed HERV-K(C4), is inserted within the gene coding for the human complement C4 in an antisense orientation (Tassabehij et al. 1994). The expression of the HERV-K(C4) RNA has been hypothesized to possibly modulate C4 expression as well as to act as a possible mechanism of defense against retroviral infections (Schneider et al 2001). Recently, it has been demonstrated that low HERV-K(C4) copy number is associated with type 1 diabetes, raising the possibility that this retroviral element contributes to functional protection against this autoimmune disease (Mason et al. 2014). Given the correlation between lower HERVK( C4) copy number and expression, it has also been proposed that HERV-K(C4) may influence C4 RNA processing and/or have an impact on other endogenous retroviral sequences (Mason et al. 2014). To have more insights into this hypothesis, we identified, lassified and characterized the HML-10 sequences that are present in the human genome GRCh37/hg19 assembly. We used the model-based software Retrotector (Sperberg et al 2007) to search HML-10 sequences in the human genome assembly GRCh37/hg19 and identified 10 HML-10 proviruses in chromosomes 1, 6, 16, 19 and Y. These proviruses were confirmed to belong to the HERV-K (HML-10) group and shown to have the Rec sequence. Out of the 10 identified HML-10s, 5 sequences have both LTRs, 4 have only 3’-LTR and 1 sequence is without LTRs. Age estimation analysis performed on the 5 sequences with both LTRs indicated that they inserted into the human genome >25 Mya ago. Five sequences conserved the primer binding site (PBS) region, all recognizing the Lys tRNA. Translational analysis showed that all proviral sequences have multiple stop codons that preclude their production of functional proteins. Phylogenetic analyses were performed with complete DNA sequences as well as with the Pol amino acid sequences and will be presented. Overall, we have identified and characterized 10 HML-10 sequences in the human genome GRCh37/hg19 assembly. Precise knowledge of all HML-10 sequences will allow further investigation of their physiological and pathological role in autoimmune diseases (Yu & Whitacre 2004), particularly their possible involvement in type 1 diabetes, giving new insights into their understanding.
Identification and genomic characterization of HERV-K (HML-10) in human genome GRCh37/hg19 assembly
CADEDDU, MARTA;GRANDI, NICOLE;TRAMONTANO, ENZO
2014-01-01
Abstract
Human endogenous retroviruses (HERVs) have been classified into three different classes I, II, III. Betaretrovirus-like sequences, including HERV-K, belong to the class II and contains ten groups, termed HML1-10. It has been reported that an HML-10 sequence, termed HERV-K(C4), is inserted within the gene coding for the human complement C4 in an antisense orientation (Tassabehij et al. 1994). The expression of the HERV-K(C4) RNA has been hypothesized to possibly modulate C4 expression as well as to act as a possible mechanism of defense against retroviral infections (Schneider et al 2001). Recently, it has been demonstrated that low HERV-K(C4) copy number is associated with type 1 diabetes, raising the possibility that this retroviral element contributes to functional protection against this autoimmune disease (Mason et al. 2014). Given the correlation between lower HERVK( C4) copy number and expression, it has also been proposed that HERV-K(C4) may influence C4 RNA processing and/or have an impact on other endogenous retroviral sequences (Mason et al. 2014). To have more insights into this hypothesis, we identified, lassified and characterized the HML-10 sequences that are present in the human genome GRCh37/hg19 assembly. We used the model-based software Retrotector (Sperberg et al 2007) to search HML-10 sequences in the human genome assembly GRCh37/hg19 and identified 10 HML-10 proviruses in chromosomes 1, 6, 16, 19 and Y. These proviruses were confirmed to belong to the HERV-K (HML-10) group and shown to have the Rec sequence. Out of the 10 identified HML-10s, 5 sequences have both LTRs, 4 have only 3’-LTR and 1 sequence is without LTRs. Age estimation analysis performed on the 5 sequences with both LTRs indicated that they inserted into the human genome >25 Mya ago. Five sequences conserved the primer binding site (PBS) region, all recognizing the Lys tRNA. Translational analysis showed that all proviral sequences have multiple stop codons that preclude their production of functional proteins. Phylogenetic analyses were performed with complete DNA sequences as well as with the Pol amino acid sequences and will be presented. Overall, we have identified and characterized 10 HML-10 sequences in the human genome GRCh37/hg19 assembly. Precise knowledge of all HML-10 sequences will allow further investigation of their physiological and pathological role in autoimmune diseases (Yu & Whitacre 2004), particularly their possible involvement in type 1 diabetes, giving new insights into their understanding.
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