A robust approach for blind detection of balanced chromosomal rearrangements with whole-genome low-coverage sequencing.
Hum Mutat
; 35(5): 625-36, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24610732
ABSTRACT
Balanced chromosomal rearrangement (or balanced chromosome abnormality, BCA) is a common chromosomal structural variation. Next-generation sequencing has been reported to detect BCA-associated breakpoints with the aid of karyotyping. However, the complications associated with this approach and the requirement for cytogenetics information has limited its application. Here, we provide a whole-genome low-coverage sequencing approach to detect BCA events independent of knowing the affected regions and with low false positives. First, six samples containing BCAs were used to establish a detection protocol and assess the efficacy of different library construction approaches. By clustering anomalous read pairs and filtering out the false-positive results with a control cohort and the concomitant mapping information, we could directly detect BCA events for each sample. Through optimizing the read depth, BCAs in all samples could be blindly detected with only 120 million read pairs per sample for data from a small-insert library and 30 million per sample for data from nonsize-selected mate-pair library. This approach was further validated using another 13 samples that contained BCAs. Our approach advances the application of high-throughput whole-genome low-coverage analysis for robust BCA detection-especially for clinical samples-without the need for karyotyping.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Translocación Genética
/
Genoma Humano
/
Aberraciones Cromosómicas
/
Secuenciación de Nucleótidos de Alto Rendimiento
Tipo de estudio:
Diagnostic_studies
/
Guideline
Límite:
Humans
Idioma:
En
Revista:
Hum Mutat
Asunto de la revista:
GENETICA MEDICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
China