Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family
Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family
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DOI：
10.1086/303012
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发表时间：
2000-08-01
影响因子：
9.8
通讯作者：
Morgan, K
中科院分区：
文献类型：
--
作者：
Greenwood, CMT;Fujiwara, TM;Morgan, K
在1987- 1989年期间，加拿大土著社区发生了结核病流行。收集了来自该社区的一个大家庭的遗传和流行病学数据，并评估了与分枝杆菌疾病易感性候选基因NRAMP1相关的证据。根据疫苗接种、年龄、既往疾病和结核菌素皮肤试验结果，将个体分为风险（责任）等级。在显性遗传模式和与高危基因型相关的相对危险度为10的假设下，结核病易感位点与位于NRAMP1远端的染色体2q35区D2S424之间的连锁最大LOD评分为3.81。在结核易感性位点和10个NRAMP1基因内变异的单倍型之间也观察到显著的连锁。尽管最年长夫妇的一个成员向其受影响的后代的传播扭曲，但没有观察到与6p染色体上主要组织相容性复杂区域的联系。将个体划分为风险等级的能力对这项研究的成功至关重要。
An epidemic of tuberculosis occurred in a community of Aboriginal Canadians during the period 1987-89. Genetic and epidemiologic data were collected on an extended family from this community, and the evidence for linkage to NRAMP1, a candidate gene for susceptibility to mycobacterial diseases, was assessed. Individuals were grouped into risk (liability) classes leased on vaccination, age, previous disease, and tuberculin skin-test results. Under the assumption of a dominant mode of inheritance and a relative risk of 10, which is associated with the high-risk genotypes, a maximum LOD score of 3.81 was observed for linkage between a tuberculosis-susceptibility locus and D2S424, which is located just distal to NRAMP1, in chromosome region 2q35. Significant linkage was also observed between a tuberculosis-susceptibility locus and a haplotype of 10 NRAMP1 intragenic variants. No linkage to the major histocompatibility-complex region on chromosome 6p was observed, despite distortion of transmission from one member of the oldest couple to their affected offspring. The ability to assign individuals to risk classes was crucial to the success of this study.