Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases.
Alistair T PagnamentaCarme CampsEdoardo GiacopuzziJohn M TaylorMona HashimEduardo CalpenaPamela J KaisakiAkiko HashimotoJing YuEdward SandersRon SchwessingerJim R HughesGerton LunterHelene DreauMatteo FerlaLukas LangeYesim KesimVassilis RagoussisDimitrios V VavoulisHolger AllroggenOlaf AnsorgeChristian BabbsSiddharth BankaBenito Baños-PiñeroDavid BeesonTal Ben-AmiDavid L BennettCeleste BentoEdward BlairCharlotte Brasch-AndersenKatherine R BullHolger CarioDeirdre CilliersValerio ContiE Graham DaviesFatima DhallaBeatriz Diez DacalYin DongJames E DunfordRenzo GuerriniAdrian L HarrisJane HartleyGeorg HollanderKassim JavaidMaureen KaneDeirdre KellyDominic KellySamantha J L KnightAlexandra Y KreinsErika M KvikstadCraig B LangmanTracy LesterKate E LinesSimon R LordXin LuSahar MansourAdnan ManzurReza MaroofianBrian MarsdenJoanne MasonSimon J McGowanDavide MeiHana MlcochovaYoshiko MurakamiAndrea H NémethSteven OkoliElizabeth OrmondroydLilian Bomme OusagerJacqueline PalaceSmita Y PatelMelissa M PentonyChris PughAboulfazl RadArchana RameshSimone G RivaIrene RobertsNoémi RoyOuti SalminenKyleen D SchillingCaroline ScottArjune SenConrad SmithMark StevensonRajesh V ThakkerStephen R F TwiggHolm H UhligRichard van WijkBarbara VonaSteven WallJing WangHugh WatkinsJaroslav ZakAnna H SchuhUsha KiniAndrew O M WilkieNiko PopitschJenny C TaylorPublished in: Genome medicine (2023)
Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.