Low-pass whole-genome sequencing in clinical cytogenetics: a validated approach.
Genet Med
; 18(9): 940-8, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-26820068
ABSTRACT
PURPOSE:
Chromosomal microarray analysis is the gold standard for copy-number variant (CNV) detection in prenatal and postnatal diagnosis. We aimed to determine whether next-generation sequencing (NGS) technology could be an alternative method for CNV detection in routine clinical application.METHODS:
Genome-wide CNV analysis (>50 kb) was performed on a multicenter group of 570 patients using a low-coverage whole-genome sequencing pipeline. These samples were referred for chromosomal analysis; CNVs (i.e., pathogenic CNVs, pCNVs) were classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS:
Overall, a total of 198 abortuses, 37 stillbirths, 149 prenatal, and 186 postnatal samples were tested. Our approach yielded results in 549 samples (96.3%). In addition to 119 subjects with aneuploidies, 103 pCNVs (74 losses and 29 gains) were identified in 82 samples, giving diagnostic yields of 53.2% (95% confidence interval 45.8, 60.5), 14.7% (5.0, 31.1), 28.5% (21.1, 36.6), and 30.1% (23.6, 37.3) in each group, respectively. Mosaicism was observed at a level as low as 25%.CONCLUSIONS:
Patients with chromosomal diseases or microdeletion/microduplication syndromes were diagnosed using a high-resolution genome-wide method. Our study revealed the potential of NGS to facilitate genetic diagnoses that were not evident in the prenatal and postnatal groups.Genet Med 18 9, 940-948.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Genoma Humano
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Trastornos de los Cromosomas
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Variaciones en el Número de Copia de ADN
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Secuenciación de Nucleótidos de Alto Rendimiento
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Guideline
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Prognostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
China