Susceptibility to childhood HTLV-1 infection is linked to chromosome 6q27
Human T-cell leukemia/lymphoma virus type 1 (HTLV-1), is a human oncoretrovirus which causes an adult T-cell leukemia/lymphoma and a chronic neuromyelopathy. We previously showed by segregation analysis that a dominant gene controlled HTLV-1 infection through breast-feeding in children of African origin, and the goal of the present study was to map this locus by a genome-wide scan. Five pedigrees of African origin with HTLV-1 seropositive children were included in the study. Linkage analysis was performed using the model-based lod-score method with the parameters estimated from our previous segregation analysis. Significant evidence for linkage (lod-score of 3.36, p=0.00004) was obtained in chomosomal region 6q27. One natural candidate gene of this region, CCR6 (Chemokine receptor 6) involved in the immunity of the digestive tract, was sequenced in one HTLV-1 seropositive child of each pedigree. Analyses of polymorphisms found in coding and flanking regions of the gene are ongoing in a sample of 59 HTLV-1 seropositive cases and 48 seronegative controls, both of African origin. This work paves the way for the identification of the molecular mechanisms of HTLV-1 infection through breast-feeding by providing molecular evidence by linkage analysis that a major locus with dominant mode of inheritance predisposes to HTLV-1 infection in children of African origin. It has also implications in the understanding of ATL which occurs in young adults who are very likely to have been infected during childhood.