A major susceptibility locus for HTLV-1 infection in childhood maps to chromosome 6q27.
Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is a human oncoretrovirus causing adult T-cell leukemia/lymphoma and chronic neuromyelopathy. We previously showed by segregation analysis that a dominant gene controls HTLV-1 infection through breast-feeding in children of African origin. Here, we report the mapping of this locus by a genome-wide linkage analysis based on the genetic model provided by segregation analysis. Five pedigrees of African origin with HTLV-1 seropositive children were included in the study. Significant evidence for linkage (LOD score of 3.36, P=0.00004) was obtained for chomosomal region 6q27 when using the robust analysis including only HTLV-1-infected subjects. When HTLV-1 seronegative children born to infected mothers were added in the analysis, a maximum LOD score of 2.79 (P=0.0002) was obtained for chomosome 2p25. This result was mostly due to the largest pedigree of our sample, which alone gave a LOD score of 2.90 (P=0.00013). We further excluded the role of exonic variants of two candidate genes located in the linked regions, CCR6 (chemokine receptor 6) in 6q27 and ID2 (inhibitor of DNA binding 2) in 2p25. Our results, mapping a major susceptibility locus to chromosome 6q27 and suggesting genetic heterogeneity with another locus at 2p25, pave the way to the determination of the molecular basis of predisposition to HTLV-1 infection in children.
Plancoulaine
Sabine
S
Laboratoire de Génétique Humaine des Maladies Infectieuses, Université Paris René Descartes, INSERM, U550, Faculté de Médecine Necker, 156 rue de Vaugirard, Paris, France. plancoulaine@necker.fr
Gessain
Antoine
A
Tortevoye
Patricia
P
Boland-Auge
Anne
A
Vasilescu
Alexandre
A
Matsuda
Fumihiko
F
Abel
Laurent
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015490:HTLV-I Infections / Q000235:genetics* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007223:Infant; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics
C106311:CCR6 protein, human; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D054399:Receptors, CCR6; D019707:Receptors, Chemokine