Genome-level analyses of Mycobacterium bovis lineages reveal the role of SNPs and antisense transcription in differential gene expression.
Genome-level analyses of Mycobacterium bovis lineages reveal the role of SNPs and antisense transcription in differential gene expression.
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DOI：
10.1186/1471-2164-14-710
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发表时间：
2013-10-17
期刊：
影响因子：
4.4
通讯作者：
Gordon SV
中科院分区：
文献类型：
--
作者：
Golby P;Nunez J;Witney A;Hinds J;Quail MA;Bentley S;Harris S;Smith N;Hewinson RG;Gordon SV
牛结核病（bTB）是一种对动物福利和生产力具有重大影响的疾病，并且具有人畜共患传播的潜力。仅在英国（GB），每年控制bTB的成本就在1亿英镑左右，目前的控制方案似乎无法阻止感染的不可阻挡的传播。可能导致这种流行病的一个方面是致病病原体牛分枝杆菌的进化。为了了解可能导致这种进化的潜在遗传变化，我们对4种牛分枝杆菌菌株进行了全面的基因组水平分析，这些菌株包含了在英国流行的病原体的主要分子类型。我们使用基因组测序、转录组分析和重组DNA技术的组合来确定在GB中循环的主要牛支原体谱系之间的遗传差异，这些遗传差异可能会产生具有实际重要性的表型差异。采用Illumina测序技术对3株牛分枝杆菌野外分离株进行了基因组测序，并利用全基因组扩增子芯片和全基因组贴片寡核苷酸芯片测定了其在体外和离体牛肺泡巨噬细胞中基因表达的特异性差异。将SNP/小碱基对的插入和缺失以及基因表达数据叠加到完全测序的牛分枝杆菌2122/97的基因组序列上，将观察到的菌株特异性基因组差异与RNA表达差异联系起来。我们表明，虽然这些菌株在基因组成和基因表达谱上表现出广泛的相似性，但它们在基因子集上表现出不同的表达。我们提供了基因组学、转录组学和功能数据来证明编码链上的同义点突变（sSNPs）可以导致相反链上反义转录物的表达，这一发现对我们如何定义“沉默”核苷酸变化具有重要意义。此外，我们表明，仅基于扩增子阵列的转录组数据可能由于反义转录物的杂交而在基因表达谱方面产生虚假的结果。总的来说，我们的数据表明，细微的遗传差异，如sSNPS，可能对基因表达和随后的表型有重要影响。
Bovine tuberculosis (bTB) is a disease with major implications for animal welfare and productivity, as well as having the potential for zoonotic transmission. In Great Britain (GB) alone, controlling bTB costs in the region of £100 million annually, with the current control scheme seemingly unable to stop the inexorable spread of infection. One aspect that may be driving the epidemic is evolution of the causative pathogen, Mycobacterium bovis. To understand the underlying genetic changes that may be responsible for this evolution, we performed a comprehensive genome-level analyses of 4 M. bovis strains that encompass the main molecular types of the pathogen circulating in GB. We have used a combination of genome sequencing, transcriptome analyses, and recombinant DNA technology to define genetic differences across the major M. bovis lineages circulating in GB that may give rise to phenotypic differences of practical importance. The genomes of three M. bovis field isolates were sequenced using Illumina sequencing technology and strain specific differences in gene expression were measured during in vitro growth and in ex vivo bovine alveolar macrophages using a whole genome amplicon microarray and a whole genome tiled oligonucleotide microarray. SNP/small base pair insertion and deletions and gene expression data were overlaid onto the genomic sequence of the fully sequenced strain of M. bovis 2122/97 to link observed strain specific genomic differences with differences in RNA expression. We show that while these strains show extensive similarities in their genetic make-up and gene expression profiles, they exhibit distinct expression of a subset of genes. We provide genomic, transcriptomic and functional data to show that synonymous point mutations (sSNPs) on the coding strand can lead to the expression of antisense transcripts on the opposing strand, a finding with implications for how we define a 'silent’ nucleotide change. Furthermore, we show that transcriptomic data based solely on amplicon arrays can generate spurious results in terms of gene expression profiles due to hybridisation of antisense transcripts. Overall our data suggest that subtle genetic differences, such as sSNPS, may have important consequences for gene expression and subsequent phenotype.
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DOI：
10.1073/pnas.0600927103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Dühring, U;Axmann, IM;Wilde, A
通讯作者：
Wilde, A
影响因子：
3.3
作者：
MONAGHAN, ML;DOHERTY, ML;QUINN, PJ
通讯作者：
QUINN, PJ
影响因子：
3.2
作者：
Smith, Noel H.;Upton, Paul
通讯作者：
Upton, Paul
影响因子：
9.4
作者：
Kamerbeek, J;Schouls, L;vanEmbden, J
通讯作者：
vanEmbden, J
DOI：
10.1099/00221287-144-5-1189
发表时间：
1998-05-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Frothingham, R;Meeker-O'Connell, WA
通讯作者：
Meeker-O'Connell, WA