Skamene E
McGill Centre for the Study of Host Resistance, Montreal General Hospital, Quebec.
Clin Invest Med. 1991 Apr;14(2):160-6.
Genetic influences on the course of mycobacterial infections during epidemics and in the endemic areas have always been suspected, but the precise nature of such genetic control and of the inherited mechanisms of susceptibility has been unknown. We have used the methods of population genetics in the mouse to discover a single dominant autosomal gene which controls the susceptibility to tuberculosis. The phenotypic expression of this gene has been defined as the nonspecific macrophage activation for bactericidal function. Using recombinant inbred strains we have mapped this gene to the centromeric part of Chromosome 1, and we have identified closely linked DNA polymorphisms (RFLP sites) which can be used as biochemical markers of innate susceptibility. It has recently become obvious that a homologous linkage group of RFLP sites is conserved in the bovine genome and also on the long arm (2q) of human Chromosome 2, suggesting the existence of a human homologue of the mouse host resistance gene. Experiments currently in progress test this hypothesis by linkage analysis of the trait of resistance and susceptibility to tuberculosis with the allelic forms of the 2q DNA markers. The identification of the human gene for susceptibility would be of major importance in the search for genetically susceptible individuals and in the development of novel strategies of specific prevention and treatment.
在流行病期间以及在地方病流行地区，遗传因素对分枝杆菌感染病程的影响一直受到怀疑，但这种遗传控制的确切性质以及遗传易感性机制尚不清楚。我们利用小鼠群体遗传学方法发现了一个单一的显性常染色体基因，它控制着对结核病的易感性。该基因的表型表达已被定义为巨噬细胞非特异性激活以发挥杀菌功能。利用重组近交系，我们已将该基因定位到1号染色体的着丝粒部分，并且我们已鉴定出紧密连锁的DNA多态性（限制性片段长度多态性位点），其可作为先天易感性的生化标记。最近已经很明显，一个同源的限制性片段长度多态性位点连锁群在牛基因组以及人类2号染色体长臂（2q）上是保守的，这表明存在小鼠宿主抗性基因的人类同源物。目前正在进行的实验通过对结核病抗性和易感性性状与2q DNA标记的等位基因形式进行连锁分析来检验这一假设。鉴定人类易感性基因在寻找遗传易感性个体以及开发特异性预防和治疗新策略方面将具有重要意义。
