T1D etiology is not clearly understood, but it lies at crossroads between genetic predisposition and environmental factors. Research on the human genome has so far identified numerous candidate sequences as genetic risk factors, most notably within the HLA (Human Leucocyte Antigen) region. However, an important part of the human genome has been neglected in the sequencing studies conducted so far, mostly including the so-called “mobile genetic elements”, which represent about half of the human genome. HERV (Human Endogenous Retroviruses) belong to this group, as retro-transposable elements. Moreover, the envelope protein from HERV-W family (HERV-W-Env) has recently been associated with T1D.

Our goal is to identify T1D genetic risk factors belonging to mobile genetic elements, with an emphasis on HERV and HERV-W-env sequences. For this purpose, we propose to use novel sequencing technologies, which have not been previously used on the genome of T1D patients. These sequencing methods enable to detect genomic regions with repetitive or homologous sequences and to identify somatic DNA recombinations or rearrangements in affected tissue.

HERV-W-env sequences and most of HERV sequences have so far been ignored by traditional sequencing methods. Sequencing technologies used in this project may allow us to identify individuals harboring HERV-W- env pathogenic DNA copies and to develop targeted therapies neutralizing the protein before the clinical onset of T1D.