Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium.
Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium.
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DOI：
10.1038/s41598-018-35506-0
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发表时间：
2018-11-21
影响因子：
4.6
通讯作者：
Reis A
中科院分区：
文献类型：
--
作者：
Popp B;Krumbiegel M;Grosch J;Sommer A;Uebe S;Kohl Z;Plötz S;Farrell M;Trautmann U;Kraus C;Ekici AB;Asadollahi R;Regensburger M;Günther K;Rauch A;Edenhofer F;Winkler J;Winner B;Reis A
诱导多能干细胞(IPSCs)的遗传完整性对于它们作为疾病模型的有效性和潜在的治疗用途至关重要。我们描述了ForIPS财团的全面分析：来自患有神经疾病和健康对照的捐赠者的IPSC集合。鉴定包括多能性确认、指纹分析、常规核型分析和分子核型分析。在大多数情况下，发现了体细胞拷贝数变异(CNV)。选择具有可用匹配供体DNA的子集进行比较外显子组测序。我们在每个突变负荷变异性很高的克隆中发现了不同等位基因频率的单核苷酸变异体(SNV)。亲本成纤维细胞中低频率的变异突出了生殖系样本的重要性。体细胞变异数与重编程、细胞类型和传代无关。与疾病基因和预测分数的比较表明，某些变异具有生物学相关性。我们表明，高通量测序具有超越SNV检测和单独评估每个克隆的要求的价值。
Genetic integrity of induced pluripotent stem cells (iPSCs) is essential for their validity as disease models and for potential therapeutic use. We describe the comprehensive analysis in the ForIPS consortium: an iPSC collection from donors with neurological diseases and healthy controls. Characterization included pluripotency confirmation, fingerprinting, conventional and molecular karyotyping in all lines. In the majority, somatic copy number variants (CNVs) were identified. A subset with available matched donor DNA was selected for comparative exome sequencing. We identified single nucleotide variants (SNVs) at different allelic frequencies in each clone with high variability in mutational load. Low frequencies of variants in parental fibroblasts highlight the importance of germline samples. Somatic variant number was independent from reprogramming, cell type and passage. Comparison with disease genes and prediction scores suggest biological relevance for some variants. We show that high-throughput sequencing has value beyond SNV detection and the requirement to individually evaluate each clone.
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端粒：一种倍性 - 敏锐的方法，用于从整个基因组测序数据中估算端粒长度。
影响因子：
4.6
作者：
Farmery JHR;Smith ML;NIHR BioResource - Rare Diseases;Lynch AG
通讯作者：
Lynch AG
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.1
作者：
Hollingsworth EW;Vaughn JE;Orack JC;Skinner C;Khouri J;Lizarraga SB;Hester ME;Watanabe F;Kosik KS;Imitola J
通讯作者：
Imitola J
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay