摘要：Abstract Background The genetic basis involved in multiple sclerosis (MS) susceptibility was not completely revealed by genome-wide association studies. Part of it could lie in repetitive sequences, as those corresponding to human Endogenous Retroviruses (HERVs). Retrovirus-like particles were isolated from {MS} patients and the genome of the MS-associated retrovirus (MSRV) was the founder of the HERV-W family. We aimed to ascertain which chromosomal origin encodes the pathogenic {ENV} protein by genomic analysis of the HERV-W insertions. Methods/results In silico analyses allowed to uncover putative open reading frames containing the specific sequence previously reported for MSRV-like envelope (env) detection. Out of the 261 genomic insertions of HERV-W env, only 9 copies harbor the specific primers and probe featuring MSRV-like env. The copy from chromosome 20 was further studied considering its size, a truncated homologue of the functional HERV-W env sequence encoding syncytin. High Resolution Melting analysis of this sequence identified two single nucleotide polymorphisms, subsequently genotyped by Taqman chemistry in 668 {MS} patients and 678 healthy controls. No significant association of these polymorphisms with {MS} risk was evidenced. Transcriptional activity of this MSRV-like env copy was detected in peripheral blood mononuclear cells from patients and controls. {RNA} expression levels of chromosome 20-specific MSRV-like env did not show significant differences between {MS} patients and controls, neither were related to genotypes of the two mentioned polymorphisms. Conclusions The lack of association with {MS} risk of the identified polymorphisms together with the transcription results discard chromosome 20 as genomic origin of MSRV-like env.
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