title: Multiple sclerosis retrovirus-like envelope gene: Role of the chromosome 20 insertion.
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.
  
  
  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.
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: Jezabel
authors.initials: J
authors.lastname: Varadé
authors.affiliation: Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: García-Montojo
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: de la Hera
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Camacho
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: M Ángel
authors.initials: MÁ
authors.lastname: García-Martínez
authors.affiliation: Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.affiliation: Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Álvarez-Lafuente
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid. Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
keywords: Genetic susceptibility; Human endogenous retrovirus HERV-W; MSRV; Multiple sclerosis