Diagnosis of copy number variation by Illumina next generation sequencing is comparable in performance to oligonucleotide array comparative genomic hybridisation

摘要

Arraycomparativegenomichybridisation(aCGH)profilingiscurrentlythegoldstandardforgeneticdiagnosisofcopynumber.Nextgenerationsequencingtechnologiesprovideanalternativeandadaptablemethodofdetectingcopynumberbycomparingthenumberofsequencereadsinnon-overlappingwindowsbetweenpatientandcontrolsamples./ppid="sp0010"DetectionofcopynumberusingtheBlueGnome8#xA0;times;#xA0;60koligonucleotideaCGHplatformwascomparedwithlowresolutionnextgenerationsequencingusingtheIlluminaGAIIxon39patientswithdevelopmentaldelayand/orlearningdifficultieswhowerereferredtotheLeedsClinicalCytogeneticsLaboratory.Sensitivityandworkflowofthetwoplatformswerecompared./ppid="sp0015"Customisedcopynumberalgorithmsassessedsequencecountsanddetectedchangesincopynumber.Imbalancesdetectedonbothplatformswerecompared./ppid="sp0020"Ofthethirty-ninepatientsanalysed,allelevenimbalancesdetectedbyarrayCGHandconfirmedbyFISHorQ-PCRwerealsodetectedbyCNV-seq.Inaddition,CNV-seqreportedonepurportedpathogeniccopynumbervariantthatwasnotdetectedbyarrayCGH./ppid="sp0025"Non-pathogenic,unconfirmedcopynumbercallsweredetectedbybothplatforms;howeverfewwereconcordantbetweenthetwo./ppid="sp0030"CNV-seqoffersanalternativetoarrayCGHforcopynumberanalysiswithresolutionandfuturecostscomparabletoconventionalarrayCGHplatformsandwithlessstringentsamplerequirements./p/div