Assessment of the incorporation of CNV surveillance into gene panel next-generation sequencing testing for inherited retinal diseases.
Assessment of the incorporation of CNV surveillance into gene panel next-generation sequencing testing for inherited retinal diseases.
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DOI：
10.1136/jmedgenet-2017-104791
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发表时间：
2018-03
影响因子：
4
通讯作者：
Black GCM
中科院分区：
文献类型：
--
作者：
Ellingford JM;Horn B;Campbell C;Arno G;Barton S;Tate C;Bhaskar S;Sergouniotis PI;Taylor RL;Carss KJ;Raymond LFL;Michaelides M;Ramsden SC;Webster AR;Black GCM
基因组下一代测序（NGS）技术的诊断使用是常见的遗传性视网膜营养不良（IRD），一个高度遗传异质性的疾病组的个人。然而，这些技术通常未能捕获导致IRD的基因组变异的完整谱，包括CNV。本研究评估了将CNV监测引入IRD一级诊断基因组NGS服务的适用性。将三种读取深度算法应用于550个参考个体的基因组NGS数据集，并将信息学策略用于质量保证和CNV过滤。CNV事件得到确认，并通过经认可的诊断实验室报告给转诊临床医生。我们确认了33个缺失和11个重复的存在，确定这些发现有助于25个个体的IRD的确认或临时分子诊断。我们发现，至少有7%的个人提到的诊断测试IRD有CNV的基因相关的临床诊断，并确定了79%的阳性预测值为CNV过滤技术。CNV分析的引入增加了IRD基因组NGS诊断测试的诊断率，提高了诊断报告的清晰度，并扩大了已知致病突变的范围。
Diagnostic use of gene panel next-generation sequencing (NGS) techniques is commonplace for individuals with inherited retinal dystrophies (IRDs), a highly genetically heterogeneous group of disorders. However, these techniques have often failed to capture the complete spectrum of genomic variation causing IRD, including CNVs. This study assessed the applicability of introducing CNV surveillance into first-tier diagnostic gene panel NGS services for IRD. Three read-depth algorithms were applied to gene panel NGS data sets for 550 referred individuals, and informatics strategies used for quality assurance and CNV filtering. CNV events were confirmed and reported to referring clinicians through an accredited diagnostic laboratory. We confirmed the presence of 33 deletions and 11 duplications, determining these findings to contribute to the confirmed or provisional molecular diagnosis of IRD for 25 individuals. We show that at least 7% of individuals referred for diagnostic testing for IRD have a CNV within genes relevant to their clinical diagnosis, and determined a positive predictive value of 79% for the employed CNV filtering techniques. Incorporation of CNV analysis increases diagnostic yield of gene panel NGS diagnostic tests for IRD, increases clarity in diagnostic reporting and expands the spectrum of known disease-causing mutations.
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DOI：
10.1093/bioinformatics/bts526
发表时间：
2012-11-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Plagnol V;Curtis J;Epstein M;Mok KY;Stebbings E;Grigoriadou S;Wood NW;Hambleton S;Burns SO;Thrasher AJ;Kumararatne D;Doffinger R;Nejentsev S
通讯作者：
Nejentsev S
影响因子：
1.7
作者：
Carnevali, Paolo;Baccash, Jonathan;Drmanac, Radoje
通讯作者：
Drmanac, Radoje
影响因子：
3.9
作者：
Johansson, Lennart F.;van Dijk, Freerk;Sikkema-Raddatz, Birgit
通讯作者：
Sikkema-Raddatz, Birgit
全基因组CNV分析：计算方法的进展。
影响因子：
3.7
作者：
Pirooznia M;Goes FS;Zandi PP
通讯作者：
Zandi PP
影响因子：
17.8
作者：
Berger, Wolfgang;Kloeckener-Gruissem, Barbara;Neidhardt, John
通讯作者：
Neidhardt, John