State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
PLoS One. 2012;7(6):e38528. doi: 10.1371/journal.pone.0038528. Epub 2012 Jun 6.
In this study, a whole-genome CombiMatrix Custom oligonucleotide tiling microarray with 90,000 probes covering six sequenced Helicobacter pylori (H. pylori) genomes was designed. This microarray was used to compare the genomic profiles of eight unsequenced strains isolated from patients with different gastroduodenal diseases in Heilongjiang province of China. Since significant genomic variation was found among these strains, an additional 76 H. pylori strains associated with different clinical outcomes were isolated from various provinces of China. These strains were tested by polymerase chain reaction to demonstrate this distinction. We identified several highly variable regions in strains associated with gastritis, gastric ulceration, and gastric cancer. These regions are associated with genes involved in the bacterial type I, type II, and type III R-M systems. They were also associated with the virB gene, which lies on the well-studied cag pathogenic island. While previous studies have reported on the diverse genetic characterization of this pathogenic island, in this study, we find that it is conserved in all strains tested by microarray. Moreover, a number of genes involved in the type IV secretion system, which is related to horizontal DNA transfer between H. pylori strains, were identified in the comparative analysis of the strain-specific genes. These findings may provide insight into new biomarkers for the prediction of gastric diseases.
在这项研究中,设计了一种包含 90,000 个探针的全基因组 CombiMatrix Custom 寡核苷酸平铺微阵列,覆盖了六个已测序的幽门螺杆菌(H. pylori)基因组。该微阵列用于比较从中国黑龙江省不同胃肠道疾病患者中分离的 8 株未测序菌株的基因组图谱。由于这些菌株之间存在显著的基因组变异,因此从中国不同省份分离了另外 76 株与不同临床结果相关的 H. pylori 菌株。这些菌株通过聚合酶链反应进行了测试,以证明这种区别。我们鉴定出了与胃炎、胃溃疡和胃癌相关的菌株中几个高度可变的区域。这些区域与细菌 I 型、II 型和 III 型 R-M 系统相关的基因有关。它们还与 virB 基因有关,该基因位于研究充分的 cag 致病岛上。虽然以前的研究报告了该致病岛的多样化遗传特征,但在本研究中,我们发现通过微阵列测试的所有菌株都保守。此外,在对菌株特异性基因的比较分析中,还鉴定出了与幽门螺杆菌菌株之间水平 DNA 转移有关的 IV 型分泌系统的许多基因。这些发现可能为预测胃部疾病提供新的生物标志物。