Whole-genome sequencing analysis of CNV using low-coverage and paired-end strategies is efficient and outperforms array-based CNV analysis.
J Med Genet
; 55(11): 735-743, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30061371
ABSTRACT
BACKGROUND:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genoma Humano
/
Genómica
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Hibridación Genómica Comparativa
/
Variaciones en el Número de Copia de ADN
/
Secuenciación Completa del Genoma
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Med Genet
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos