Construction and application of a zebrafish array comparative genomic hybridization platform.

Construction and application of a zebrafish array comparative genomic hybridization platform.
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DOI:
10.1002/gcc.20623
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发表时间:
2009-02
影响因子:
3.7
通讯作者:
Lee, Charles
Lee, Charles
中科院分区:
医学2区
文献类型:
--
作者:
Freeman, Jennifer L.;Ceol, Craig;Feng, Hui;Langenau, David M.;Belair, Cassandra;Stern, Howard M.;Song, Anhua;Paw, Barry H.;Look, A. Thomas;Zhou, Yi;Zon, Leonard I.;Lee, Charles

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斑马鱼正在成为研究人类发育和疾病遗传学的重要模型系统。每个突变模型的基础遗传改变可以以单碱基变化、平衡染色体重排或遗传不平衡的形式存在。为了以无偏的全基因组方式检测遗传不平衡,可以使用阵列比较基因组杂交(CGH)。我们已经开发了一个5 Mb分辨率的阵列计算全息平台,专门为斑马鱼。该平台包含286个BAC克隆,富含人类癌基因和肿瘤抑制基因的正向序列。每个BAC克隆都经过末端测序,并在细胞遗传学上分配到斑马鱼基因组内的特定位置,从而易于将阵列CGH数据与当前版本的基因组组装体整合。该平台已应用于三种斑马鱼癌症模型。在每个模型中检测到显著的基因组不平衡,鉴定了可能在肿瘤发生中起作用的不同区域。因此,这个平台应该是一个有用的资源,遗传解剖的其他斑马鱼发育和疾病模型,以及未来的阵列CGH平台开发的基准。
The zebrafish is emerging as a prominent model system for studying the genetics of human development and disease. Genetic alterations that underlie each mutant model can exist in the form of single base changes, balanced chromosomal rearrangements, or genetic imbalances. To detect genetic imbalances in an unbiased genome-wide fashion, array comparative genomic hybridization (CGH) can be used. We have developed a 5 Mb resolution array CGH platform specifically for the zebrafish. This platform contains 286 BAC clones, enriched for orthologous sequences of human oncogenes and tumor suppressor genes. Each BAC clone has been end-sequenced and cytogenetically assigned to a specific location within the zebrafish genome, allowing for ease of integration of array CGH data with the current version of the genome assembly. This platform has been applied to three zebrafish cancer models. Significant genomic imbalances were detected in each model, identifying different regions which may potentially play a role in tumorigenesis. Hence, this platform should be a useful resource for genetic dissection of additional zebrafish developmental and disease models as well as a benchmark for future array CGH platform development.
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