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Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies.
Lowther, Chelsea; Valkanas, Elise; Giordano, Jessica L; Wang, Harold Z; Currall, Benjamin B; O'Keefe, Kathryn; Pierce-Hoffman, Emma; Kurtas, Nehir E; Whelan, Christopher W; Hao, Stephanie P; Weisburd, Ben; Jalili, Vahid; Fu, Jack; Wong, Isaac; Collins, Ryan L; Zhao, Xuefang; Austin-Tse, Christina A; Evangelista, Emily; Lemire, Gabrielle; Aggarwal, Vimla S; Lucente, Diane; Gauthier, Laura D; Tolonen, Charlotte; Sahakian, Nareh; Stevens, Christine; An, Joon-Yong; Dong, Shan; Norton, Mary E; MacKenzie, Tippi C; Devlin, Bernie; Gilmore, Kelly; Powell, Bradford C; Brandt, Alicia; Vetrini, Francesco; DiVito, Michelle; Sanders, Stephan J; MacArthur, Daniel G; Hodge, Jennelle C; O'Donnell-Luria, Anne; Rehm, Heidi L; Vora, Neeta L; Levy, Brynn; Brand, Harrison; Wapner, Ronald J; Talkowski, Michael E.
  • Lowther C; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
  • Valkanas E; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Program in Biological and Biomedical Sciences, Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
  • Giordano JL; Department of Obstetrics & Gynecology, Columbia University Medical Center, New York, NY, USA.
  • Wang HZ; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Currall BB; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
  • O'Keefe K; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pierce-Hoffman E; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kurtas NE; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
  • Whelan CW; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hao SP; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Weisburd B; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Jalili V; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Fu J; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
  • Wong I; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Collins RL; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Program in Bioinformatics and Integrative Genomics, Division of Medical Sciences, Harvard Medical School, Boston, MA,
  • Zhao X; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
  • Austin-Tse CA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Pathology, Harvard Medical School, Boston, MA, USA.
  • Evangelista E; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lemire G; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Aggarwal VS; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
  • Lucente D; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Gauthier LD; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Data Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tolonen C; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Data Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Sahakian N; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Data Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Stevens C; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • An JY; School of Biosystem and Biomedical Science, Korea University, Seoul, South Korea.
  • Dong S; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • Norton ME; Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.
  • MacKenzie TC; Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Devlin B; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Gilmore K; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Powell BC; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Brandt A; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Vetrini F; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • DiVito M; Department of Obstetrics & Gynecology, Columbia University Medical Center, New York, NY, USA.
  • Sanders SJ; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
  • MacArthur DG; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Centre for Population Genomics, Garvan Institute of Medical Research, and University of New South Wales Sydney, Sydney
  • Hodge JC; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • O'Donnell-Luria A; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
  • Rehm HL; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Vora NL; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Levy B; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
  • Brand H; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
  • Wapner RJ; Department of Obstetrics & Gynecology, Columbia University Medical Center, New York, NY, USA.
  • Talkowski ME; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Program in Biological and Biomedical Sciences, Divis
Am J Hum Genet ; 110(9): 1454-1469, 2023 09 07.
Article en En | MEDLINE | ID: mdl-37595579
ABSTRACT
Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests karyotype, chromosomal microarray (CMA), and exome sequencing (ES). To assess the clinical utility of GS, we compared its diagnostic yield against these three tests in 1,612 quartet families including an individual with ASD and in 295 prenatal families. Our GS analytic framework identified a diagnostic variant in 7.8% of ASD probands, almost 2-fold more than CMA (4.3%) and 3-fold more than ES (2.7%). However, when we systematically captured copy-number variants (CNVs) from the exome data, the diagnostic yield of ES (7.4%) was brought much closer to, but did not surpass, GS. Similarly, we estimated that GS could achieve an overall diagnostic yield of 46.1% in unselected FSAs, representing a 17.2% increased yield over karyotype, 14.1% over CMA, and 4.1% over ES with CNV calling or 36.1% increase without CNV discovery. Overall, GS provided an added diagnostic yield of 0.4% and 0.8% beyond the combination of all three standard-of-care tests in ASD and FSAs, respectively. This corresponded to nine GS unique diagnostic variants, including sequence variants in exons not captured by ES, structural variants (SVs) inaccessible to existing standard-of-care tests, and SVs where the resolution of GS changed variant classification. Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trastorno del Espectro Autista Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Pregnancy Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trastorno del Espectro Autista Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Pregnancy Idioma: En Año: 2023 Tipo del documento: Article