Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies.
EBioMedicine
; 23: 150-159, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28865746
ABSTRACT
Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 ß-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testes Genéticos
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Predisposição Genética para Doença
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Estudos de Associação Genética
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Sequenciamento de Nucleotídeos em Larga Escala
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Técnicas de Genotipagem
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Hemoglobinopatias
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Adolescent
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Adult
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Humans
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2017
Tipo de documento:
Article