Although such individuals are relatively uncommon, the study of discordant monozygotic twins offers substantially improved experimental control (i.e., an individual affected with CFS and their well monozygotic twin) [12]. We Sirolimus manufacturer are aware of one previous study that assessed 22 pairs of monozygotic twins discordant for CFS for indices of past and current viral infection

(BK virus; cytomegalovirus; Epstein-Barr virus; hepatitis C virus; herpes simplex virus 1 and 2; human herpes virus 6, 7, and 8; JC virus; parvovirus B19; and varicella zoster virus): no significant or clinically important differences were found between affected and unaffected twins [13]. An additional limitation has been the reliance on assays for specific infectious agents. Viruses have traditionally been identified by culture techniques and more recently via a variety of molecular approaches. However, these methods have severe limitations and leave many viruses undetected. We have developed a complete “”metagenomic”" system for systematic identification of unknown viruses. The discovery pipeline has four components: virus enrichment, amplification of genomic viral DNA or RNA, large scale sequencing, and identification of Bioactive Compound Library screening known and novel viral sequences using bioinformatics.

This powerful strategy has identified two new viruses, human bocavirus [14] and KI polyomavirus [15] which cause acute respiratory illness in children. In this study, 45 pairs of monozygotic twins mafosfamide discordant for chronic fatigue were used in an exhaustive study to identify risk factors [12]. We report here the results of screening for viruses in these samples using metagenomic sequencing. Deep sequencing revealed the presence of several viruses in cases with chronic fatigue, particularly GB virus C. Results The patient set consisted of 45 pairs of monozygotic twins discordant for clinically-evaluated chronic fatiguing illness (Table 1). Most pairs were female (89%),

and the median age at evaluation was 51 years. Of the affected twins, 32 met criteria for CFS and 13 for ICF with a median duration of chronic fatigue of 8 years with no significant difference between affected twins with CFS and ICF (p = 0.75). Body mass index was similar between the affected and unaffected twins. Affected twins had significantly worse physical and mental functioning on the SF-36 [16] and reported significantly greater current fatigue. The mean functioning of affected twins was over a standard deviation worse than Swedish norms whereas the unaffected twins were similar to Swedish norms (http://​www.​sf-36.​org/​nbscalc/​index.​shtml, accessed 12 December 2008). Table 1 Description of 45 monozygotic twin pairs discordant for chronic impairing fatigue.