Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats
Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats
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DOI：
10.1099/00221287-144-5-1189
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发表时间：
1998-05-01
期刊：
影响因子：
--
通讯作者：
Meeker-O'Connell, WA
中科院分区：
文献类型：
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作者：
Frothingham, R;Meeker-O'Connell, WA
含有可变数目串联重复序列的基因位点（VNTR位点）构成了人类基因定位和鉴定、法医分析和亲子鉴定的基础。细菌串联重复序列的可变性尚未得到系统的研究。对结核分枝杆菌基因组中的11个串联重复位点进行了分析。5个主要的多态串联重复（MPTR）位点包含15bp重复序列，相邻拷贝的序列差异较大。6个精确串联重复序列（ETR）位点包含大的DNA重复序列，相邻重复序列相同。将这11个基因座扩增到48株中，测定每个基因座的串联重复次数。分析菌株包括结核分枝杆菌、牛分枝杆菌、非洲分枝杆菌和微分枝杆菌25株野生型菌株和23株牛分枝杆菌卡介苗减毒亚株。5个MPTR位点中的1个和6个ETR位点均存在串联重复序列插入或缺失的长度多态性。大多数ETR位点位于基因间区，拷贝数可能影响下游基因的表达。每个ETR位点在面板中有多个等位基因。在结核分枝杆菌复合体的25株野生型菌株中鉴定出22个不同的等位基因图谱，在23株牛分枝杆菌卡介苗亚株中鉴定出5个等位基因图谱。从不同实验室获得的特定参考菌株的多个分离株的分析表明，等位基因谱具有可重复性和稳定性。VNTR分型可能对菌株分化和细菌进化研究普遍有用。
Genetic loci containing variable numbers of tandem repeats (VNTR loci) form the basis for human gene mapping and identification, forensic analysis and paternity testing. The variability of bacterial tandem repeats has not been systematically studied. Eleven tandem repeat loci in the M. tuberculosis genome were analysed. Five major polymorphic tandem repeat (MPTR) loci contained 15-bp repeats with substantial sequence variation in adjacent copies. Six exact tandem repeat (ETR) loci contained large DNA repeats with identical sequences in adjacent repeats. These 11 loci were amplified in 48 strains to determine the number of tandem repeats at each locus. The strains analysed included 25 wild-type strains of M. tuberculosis, M. bovis, M. africanum and M. microti and 23 substrains of the attenuated M. bovis BCG vaccine. One of the five MPTR loci and all six ETR loci had length polymorphisms corresponding to insertions or deletions of tandem repeats. Most ETR loci were located in intergenic regions where copy number may influence expression of downstream genes. Each ETR locus had multiple alleles in the panel. Combined analysis identified 22 distinct allele profiles in 25 wildtype strains of the M. tuberculosis complex and five allele profiles in 23 M. bovis BCG substrains. Allele profiles were reproducible and stable, as demonstrated by analyses of multiple isolates of particular reference strains obtained from different laboratories. VNTR typing may be generally useful for strain differentiation and evolutionary studies in bacteria.