Human endogenous retroviruses (HERVs) have received much attention for their implications in the etiology of many human diseases and their profound effect on evolution. Notably, recent studies have highlighted associations between HERVs expression and cancers [1], autoimmunity [2] and neurological [3] conditions. Their repetitive nature makes their study particularly challenging, where expression studies have largely focused on individual loci [4] or general trends within families [5, 6, 7]. To refine our understanding of HERVs activity, we introduce here a new microarray, HERV-V3, that offers an almost complete coverage of HERVs and their ancestors (mammalian apparent LTR-retrotransposons, MALRs) at the locus level.
This was made possible by the careful detection and annotation of genomic HERVs/MALRs sequences as well as the development of a new hybridization model, allowing the optimization of probe performances and the control of cross-reactions. Although no gold standard in HERVs measurement exists to validate the array, HERV-V3 analytical performances were comparable to commercial Affymetrix arrays, and for a selection of tissue/pathological specific loci, the patterns of expression found on HERV-V3 were consistent with those reported in the literature.
Overall design: HERV-V3 technical performances were evaluated on the MAQC samples, composed of two independent samples (A, Stratagene Universal RNA, and B, Ambion Human Brain RNA) from which two titration samples were generated (C and D, consisting of 3:1 and 1:3 ratios of A to B, respectively). Each sample was performed in technical triplicate. The biological validation was performed on three different tissues (colon, placenta and prostate) and two primary human cell lines (OSCAR and EBJ14).
Less...