In:
Journal of Medical Genetics, BMJ, Vol. 55, No. 11 ( 2018-11), p. 735-743
Abstract:
Copy number variation (CNV) analysis is an integral component of the study of human genomes in both research and clinical settings. Array-based CNV analysis is the current first-tier approach in clinical cytogenetics. Decreasing costs in high-throughput sequencing and cloud computing have opened doors for the development of sequencing-based CNV analysis pipelines with fast turnaround times. We carry out a systematic and quantitative comparative analysis for several low-coverage whole-genome sequencing (WGS) strategies to detect CNV in the human genome. Methods We compared the CNV detection capabilities of WGS strategies (short insert, 3 kb insert mate pair and 5 kb insert mate pair) each at 1×, 3× and 5× coverages relative to each other and to 17 currently used high-density oligonucleotide arrays. For benchmarking, we used a set of gold standard (GS) CNVs generated for the 1000 Genomes Project CEU subject NA12878. Results Overall, low-coverage WGS strategies detect drastically more GS CNVs compared with arrays and are accompanied with smaller percentages of CNV calls without validation. Furthermore, we show that WGS (at ≥1× coverage) is able to detect all seven GS deletion CNVs 〉 100 kb in NA12878, whereas only one is detected by most arrays. Lastly, we show that the much larger 15 Mbp Cri du chat deletion can be readily detected with short-insert paired-end WGS at even just 1× coverage. Conclusions CNV analysis using low-coverage WGS is efficient and outperforms the array-based analysis that is currently used for clinical cytogenetics.
Type of Medium:
Online Resource
ISSN:
0022-2593
,
1468-6244
DOI:
10.1136/jmedgenet-2018-105272
DOI:
10.1136/jmedgenet-2018-105272.supp14
DOI:
10.1136/jmedgenet-2018-105272.supp7
DOI:
10.1136/jmedgenet-2018-105272.supp1
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10.1136/jmedgenet-2018-105272.supp2
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10.1136/jmedgenet-2018-105272.supp8
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10.1136/jmedgenet-2018-105272.supp9
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10.1136/jmedgenet-2018-105272.supp3
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10.1136/jmedgenet-2018-105272.supp4
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10.1136/jmedgenet-2018-105272.supp5
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10.1136/jmedgenet-2018-105272.supp11
DOI:
10.1136/jmedgenet-2018-105272.supp12
DOI:
10.1136/jmedgenet-2018-105272.supp13
DOI:
10.1136/jmedgenet-2018-105272.supp16
DOI:
10.1136/jmedgenet-2018-105272.supp6
DOI:
10.1136/jmedgenet-2018-105272.supp10
DOI:
10.1136/jmedgenet-2018-105272.supp15
Language:
English
Publisher:
BMJ
Publication Date:
2018
detail.hit.zdb_id:
2009590-9
SSG:
12
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