Lavebratt C, Apt A S, Nikonenko B V, Schalling M, Schurr E
Neurogenetics Unit, Center for Molecular Medicine, Karolinska Hospital, 171 76 Stockholm, Sweden.
J Infect Dis. 1999 Jul;180(1):150-5. doi: 10.1086/314843.
Genetic factors play a role in host response to infection with Mycobacterium tuberculosis, the number one infectious killer worldwide. Mice of the inbred strains I/St and A/Sn show significant differences in disease severity after intravenous injection of a lethal dose of the virulent human isolate M. tuberculosis H37Rv. Following challenge with H37Rv, only I/St mice have rapid body weight loss and short survival times. A genome wide analysis for linkage with body weight after M. tuberculosis H37Rv infection was done in (A/SnxI/St)F1xI/St mice. Among females, quantitative trait loci (QTLs) on chromosomes 9 and 3 were significantly linked to postinfection body weight (logarithm of the odds ratio [LOD] scores of 6.68 and 3.92, respectively). Suggestive linkages were found for QTLs on chromosomes 8 and 17 (LOD scores of 3.01 and 2.95, respectively). For males, QTLs on chromosomes 5 and 10 showed suggestive linkages (LOD scores of 3.03 and 2.31, respectively). These linkages can be used to identify candidate regions for tuberculosis susceptibility loci in the human genome.
遗传因素在宿主对结核分枝杆菌感染的反应中发挥作用，结核分枝杆菌是全球头号感染性杀手。近交系I/St和A/Sn小鼠在静脉注射致死剂量的强毒力人源分离株结核分枝杆菌H37Rv后，疾病严重程度存在显著差异。在用H37Rv攻击后，只有I/St小鼠体重迅速下降且存活时间短。在(A/SnxI/St)F1xI/St小鼠中对结核分枝杆菌H37Rv感染后与体重的连锁进行了全基因组分析。在雌性小鼠中，9号和3号染色体上的数量性状基因座（QTL）与感染后体重显著连锁（优势比对数[LOD]分数分别为6.68和3.92）。在8号和17号染色体上发现了QTL的提示性连锁（LOD分数分别为3.01和2.95）。对于雄性小鼠，5号和10号染色体上的QTL显示出提示性连锁（LOD分数分别为3.03和2.31）。这些连锁可用于确定人类基因组中结核病易感基因座的候选区域。
