Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis.
Monica Hsiung WojcikGabrielle LemireMaha S ZakiMariel WissmanWathone WinSue WhiteBen WeisburdLeigh B WaddellJeffrey M VerboonGrace E VanNoyAna TöpfTiong Yang TanVolker StraubSarah L StentonHana SnowMoriel Singer-BerkJosh SilverShirlee ShrilEleanor G SeabyRonen SchneiderVijay G SankaranAlba Sanchis-JuanKathryn A RussellKarit ReinsonGianina RavenscroftEric A PierceEmily M PlaceSander PajusaluLynn PaisKatrin ÕunapIkeoluwa Osei-OwusuVolkan OkurKaisa Teele OjaMelanie O'LearyEmily O'HeirChantal MorelRhett G MarchantBrian E MangilogJill A MaddenDaniel MacArthurAlysia LovgrenJordan P Lerner-EllisJasmine LinNigel LaingFriedhelm HildebrandtEmily GroopmanJulia GoodrichJoseph G GleesonRoula GhaouiCasie A GenettiHanna T GazdaVijay S GaneshMythily GanapathyLyndon GallacherJack FuEmily EvangelistaEleina EnglandSandra DonkervoortStephanie DiTroiaSandra T CooperWendy K ChungJohn ChrisodoulouKatherine R ChaoLiam D CatoKinga M BujakowskaSamantha J BryenHarrison BrandCarsten BonnemannAlan H BeggsSamantha M BaxterPankaj B AgrawalMichael TalkowskiChrissy Austin-TseHeidi L RehmAnne O'Donnell-LuriaPublished in: medRxiv : the preprint server for health sciences (2023)
We describe the diagnostic yield of GS in a large and diverse cohort, illustrating several types of pathogenic variation eluding ES or other techniques. Our results reveal a higher diagnostic yield of GS, supporting the utility of a genome-first approach, with consideration of GS as a secondary or tertiary test when higher-resolution structural variant analysis is needed or there is a strong clinical suspicion for a condition and prior targeted genetic testing has been negative.