Plancoulaine Sabine, Gessain Antoine, Tortevoye Patricia, Boland-Auge Anne, Vasilescu Alexandre, Matsuda Fumihiko, Abel Laurent
Laboratoire de Génétique Humaine des Maladies Infectieuses, Université Paris René Descartes, INSERM, U550, Faculté de Médecine Necker, 156 rue de Vaugirard, Paris, France.
Hum Mol Genet. 2006 Nov 15;15(22):3306-12. doi: 10.1093/hmg/ddl406. Epub 2006 Oct 6.
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.
人类T细胞白血病/淋巴瘤病毒1型（HTLV-1）是一种人类嗜肝逆转录病毒，可导致成人T细胞白血病/淋巴瘤和慢性神经脊髓病。我们之前通过分离分析表明，一个显性基因通过母乳喂养控制非洲裔儿童的HTLV-1感染。在此，我们报告基于分离分析提供的遗传模型，通过全基因组连锁分析对该基因座进行的定位。该研究纳入了5个有HTLV-1血清阳性儿童的非洲裔家系。当仅对HTLV-1感染个体进行稳健分析时，在染色体区域6q27获得了显著的连锁证据（LOD评分为3.36，P = 0.00004）。当将感染母亲所生的HTLV-1血清阴性儿童纳入分析时，在染色体2p25获得了最高LOD评分为2.79（P = 0.0002）。这一结果主要归因于我们样本中最大的家系，其单独就给出了LOD评分为2.90（P = 0.00013）。我们进一步排除了位于连锁区域的两个候选基因的外显子变异的作用，即6q27区域的CCR6（趋化因子受体6）和2p25区域的ID2（DNA结合抑制剂2）。我们的结果将一个主要的易感基因座定位到染色体6q27，并提示与2p25处的另一个基因座存在遗传异质性，为确定儿童HTLV-1感染易感性的分子基础铺平了道路。
