Genome Sequencing of 161 Mycobacterium Tuberculosis Isolates from China Identifies Genes and Intergenic Regions Associated with Drug Resistance

Overview

Journal Nat Genet

Specialty Genetics

Date 2013 Sep 3

PMID 23995137

Citations 195

Authors

Hongtai Zhang

Dongfang Li

Lili Zhao

Joy Fleming

Nan Lin

Ting Wang

Zhangyi Liu

Chuanyou Li

Nicholas Galwey

Jiaoyu Deng

Ying Zhou

Yuanfang Zhu

Yunrong Gao

Tong Wang

Shihua Wang

Yufen Huang

Ming Wang

Qiu Zhong

Lin Zhou

Tao Chen

Jie Zhou

Ruifu Yang

Guofeng Zhu

Haiying Hang

Jia Zhang

Fabin Li

Kanglin Wan

Jun Wang

Xian-En Zhang

Lijun Bi

Affiliations

Soon will be listed here.

Abstract

The worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis threatens to make this disease incurable. Drug resistance mechanisms are only partially understood, and whether the current understanding of the genetic basis of drug resistance in M. tuberculosis is sufficiently comprehensive remains unclear. Here we sequenced and analyzed 161 isolates with a range of drug resistance profiles, discovering 72 new genes, 28 intergenic regions (IGRs), 11 nonsynonymous SNPs and 10 IGR SNPs with strong, consistent associations with drug resistance. On the basis of our examination of the dN/dS ratios of nonsynonymous to synonymous SNPs among the isolates, we suggest that the drug resistance-associated genes identified here likely contain essentially all the nonsynonymous SNPs that have arisen as a result of drug pressure in these isolates and should thus represent a near-complete set of drug resistance-associated genes for these isolates and antibiotics. Our work indicates that the genetic basis of drug resistance is more complex than previously anticipated and provides a strong foundation for elucidating unknown drug resistance mechanisms.

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