Diagnosis of copy number variation by Illumina next generation sequencing is comparable in performance to oligonucleotide array comparative genomic hybridisation.
Genomics
; 102(3): 174-81, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23598253
ABSTRACT
Array comparative genomic hybridisation (aCGH) profiling is currently the gold standard for genetic diagnosis of copy number. Next generation sequencing technologies provide an alternative and adaptable method of detecting copy number by comparing the number of sequence reads in non-overlapping windows between patient and control samples. Detection of copy number using the BlueGnome 8×60k oligonucleotide aCGH platform was compared with low resolution next generation sequencing using the Illumina GAIIx on 39 patients with developmental delay and/or learning difficulties who were referred to the Leeds Clinical Cytogenetics Laboratory. Sensitivity and workflow of the two platforms were compared. Customised copy number algorithms assessed sequence counts and detected changes in copy number. Imbalances detected on both platforms were compared. Of the thirty-nine patients analysed, all eleven imbalances detected by array CGH and confirmed by FISH or Q-PCR were also detected by CNV-seq. In addition, CNV-seq reported one purported pathogenic copy number variant that was not detected by array CGH. Non-pathogenic, unconfirmed copy number calls were detected by both platforms; however few were concordant between the two. CNV-seq offers an alternative to array CGH for copy number analysis with resolution and future costs comparable to conventional array CGH platforms and with less stringent sample requirements.
Palavras-chave
CNV; Copy number; Expectationmaximization; EM; FISH; GaII x; Illumina; Illumina Genome Analyzer IIx; MLPA; NGS; Next generation sequencing; OMIM; Online Mendelian Inheritance in Man; Q-PCR; Quantitative PCR; copy number variation; fluorescent in situ hybridisation; multiplex ligation-dependent probe amplification; next generation sequencing
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Análise de Sequência com Séries de Oligonucleotídeos
/
Hibridização Genômica Comparativa
/
Variações do Número de Cópias de DNA
/
Sequenciamento de Nucleotídeos em Larga Escala
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
/
Child
/
Child, preschool
/
Humans
Idioma:
En
Revista:
Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido