Copy number variation contributes to cryptic genetic variation in outbreak lineages of Cryptococcus gattii from the North American Pacific Northwest.
Copy number variation contributes to cryptic genetic variation in outbreak lineages of Cryptococcus gattii from the North American Pacific Northwest.
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DOI：
10.1186/s12864-016-3044-0
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发表时间：
2016-09-02
期刊：
影响因子：
4.4
通讯作者：
Gibbons JG
中科院分区：
文献类型：
--
作者：
Steenwyk JL;Soghigian JS;Perfect JR;Gibbons JG
拷贝数变异体（CNV）是一类结构变异体（SV），并且被定义为与参考基因组相比以可变拷贝数存在的DNA片段。生物信息学方法和测序技术的最新进展使得全基因组CNV的高分辨率定量成为可能。在病原真菌中，SV已被证明可以改变基因表达，影响宿主特异性，并驱动杀菌剂抗性，但很少有人专门关注CNVs。利用公开的测序数据，我们在212个格特隐球菌基因组中鉴定了90个分离株，这些分离株属于VGII亚组，这些亚组导致了最近在北美太平洋西北部的致命疫情。我们为每个样本生成CNV谱，以研究CNV在C.加提。我们从212 C. gattii分离物的种群结构分析。三个集群代表北美太平洋西北部的VGIIa、VGIIb和VGIIc亚群。CNV是生物信息学预测的，并且影响C. Gattii VGII亚组基因组。67个位点，包括58个基因，表现出高度分歧的模式之间的VGII亚组的拷贝数变异。不同CN可变基因内的PFam结构域的分析揭示了与运输、细胞壁组织和外部封装结构相关的蛋白质结构域的富集。CNVs可能导致了C. Gattii VGIIa、VGIIb和VGIIc亚群。与群体分化的CNVs重叠的基因富集了几个毒力相关的功能术语。这些结果揭示了新的候选基因，以研究C。格特氏菌致病性本文的在线版本（doi：10.1186/s12864-016-3044-0）包含补充材料，可供授权用户使用。
Copy number variants (CNVs) are a class of structural variants (SVs) and are defined as fragments of DNA that are present at variable copy number in comparison with a reference genome. Recent advances in bioinformatics methodologies and sequencing technologies have enabled the high-resolution quantification of genome-wide CNVs. In pathogenic fungi SVs have been shown to alter gene expression, influence host specificity, and drive fungicide resistance, but little attention has focused specifically on CNVs. Using publicly available sequencing data, we identified 90 isolates across 212 Cryptococcus gattii genomes that belong to the VGII subgroups responsible for the recent deadly outbreaks in the North American Pacific Northwest. We generated CNV profiles for each sample to investigate the prevalence and function of CNV in C. gattii. We identified eight genetic clusters among publicly available Illumina whole genome sequence data from 212 C. gattii isolates through population structure analysis. Three clusters represent the VGIIa, VGIIb, and VGIIc subgroups from the North American Pacific Northwest. CNV was bioinformatically predicted and affected ~300–400 Kilobases (Kb) of the C. gattii VGII subgroup genomes. Sixty-seven loci, encompassing 58 genes, showed highly divergent patterns of copy number variation between VGII subgroups. Analysis of PFam domains within divergent CN variable genes revealed enrichment of protein domains associated with transport, cell wall organization and external encapsulating structure. CNVs may contribute to pathological and phenotypic differences observed between the C. gattii VGIIa, VGIIb, and VGIIc subpopulations. Genes overlapping with population differentiated CNVs were enriched for several virulence related functional terms. These results uncover novel candidate genes to examine the genetic and functional underpinnings of C. gattii pathogenicity. The online version of this article (doi:10.1186/s12864-016-3044-0) contains supplementary material, which is available to authorized users.
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DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
6.4
作者：
Chen, SCA;Muller, M;Sorrell, TC
通讯作者：
Sorrell, TC
DOI：
10.1534/g3.112.004242
发表时间：
2013-03
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Chen YL;Lehman VN;Lewit Y;Averette AF;Heitman J
通讯作者：
Heitman J
影响因子：
7
作者：
Bickhart, Derek M.;Hou, Yali;Liu, George E.
通讯作者：
Liu, George E.
影响因子：
3.6
作者：
Brown, JS;Gilliland, SM;Holden, DW
通讯作者：
Holden, DW