ArticleNature genetics2017
The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.
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In one paragraph
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed, 1 pooled it
42.3field-weighted citation impact, top 1% of its field
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Who cites it
171 citing papers in PubMed, 1 synthesis or guideline pooled it, 350 citations in OpenAlex.
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- Long-read genome sequencing resolves the breakpoints of a chromosome 8;22 balanced translocation in NF2-related schwannomatosis.Scientific reports · 2025Article
- Structural variants in the 3D genome as drivers of disease.Nature reviews. Genetics · 2025Review
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- Inter-chromosomal insertions at Xq27.1 associated with retinal dystrophy induce dysregulation of LINC00632 and CDR1as/ciRS-7.American journal of human genetics · 2025Article
- Genomic Balancing Act: deciphering DNA rearrangements in the complex chromosomal aberration involving 5p15.2, 2q31.1, and 18q21.32.European journal of human genetics : EJHG · 2025Article
- Rare germline structural variants increase risk for pediatric solid tumors.Science (New York, N.Y.) · 2025Article
- Chromoplexy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Integrating genome and transcriptome analysis to decipher balanced structural variants in unsolved cases of neurodevelopmental disorders.Frontiers in genetics · 2025Article
- Chromothripsis.Methods in molecular biology (Clifton, N.J.) · 2025Review
111 more citing papers are in PubMed but not listed here.
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Authors and funding
149 authors at 20 institutions in 16 countries.
Claire RedinMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Harrison BrandMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ryan L CollinsMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000-0003-1268-9995
Tammy KamminDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Elyse MitchellDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Jennelle C HodgeDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Carrie HanscomMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Vamsee PillalamarriMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Catarina M SeabraMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mary-Alice AbbottMedical Genetics, Baystate Medical Center, Springfield, Massachusetts, USA.
Omar A Abdul-RahmanDepartment of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Erika AbergMaritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia, Canada.
Rhett AdleyMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Sofia L Alcaraz-EstradaMedical Genomics Division, Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico.
Fowzan S AlkurayaDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.ORCID 0000-0003-4158-341X
Yu AnMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mary-Anne AndersonCenter for Human Genetic Research DNA and Tissue Culture Resource, Boston, Massachusetts, USA.
Caroline AntolikMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Kwame Anyane-YeboaDivision of Clinical Genetics, Columbia University Medical Center, New York, New York, USA.
Joan F AtkinDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Tina BartellDepartment of Genetics, Kaiser Permanente, Sacramento, California, USA.
Jonathan A BernsteinDepartment of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
Elizabeth BeyerDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Ian BlumenthalMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ernie M H F BongersDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Eva H BrilstraDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Chester W BrownDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Hennie T BrüggenwirthDepartment of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, the Netherlands.
Bert CallewaertCenter for Medical Genetics, Ghent University, Ghent, Belgium.
Colby ChiangMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-4113-6065
Ken CorningGreenwood Genetic Center, Columbia, South Carolina, USA.
Helen CoxWest Midlands Regional Clinical Genetics Unit, Birmingham Women's Hospital, Edgbaston, Birmingham, UK.
Edwin CuppenDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Benjamin B CurrallMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Tom CushingDivision of Pediatric Genetics, Department of Pediatrics, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA.
Dezso DavidDepartment of Human Genetics, National Health Institute Doutor Ricardo Jorge, Lisbon, Portugal.
Matthew A DeardorffDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Annelies DheedeneCenter for Medical Genetics, Ghent University, Ghent, Belgium.
Marc D'HoogheDepartment of Neurology and Child Neurology, Algemeen Ziekenhuis Sint-Jan, Brugge, Belgium.
Bert B A de VriesDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Dawn L EarlSeattle Children's, Seattle, Washington, USA.
Heather L FergusonDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Heather FisherMount Sinai West Hospital, New York, New York, USA.
David R FitzPatrickMRC Human Genetics Unit, Institute of Genetic and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Pamela GerrolDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Daniela GiachinoMedical Genetics Unit, Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
Joseph T GlessnerMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Troy GliemDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Margo GradyUW Cancer Center at ProHealth Care, Waukesha, Wisconsin, USA.
Brett H GrahamDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.ORCID 0000-0001-8451-8154
Cristin GriffisDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Karen W GrippSidney Kimmel Medical School at Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Andrea L GropmanDivision of Neurogenetics and Developmental Pediatrics, Children's National Medical Center, Washington, DC, USA.
Andrea Hanson-KahnDepartment of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
David J HarrisDivision of Genetics, Boston Children's Hospital, Boston, Massachusetts, USA.
Mark A HaydenDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Rosamund HillDepartment of Neurology, Auckland City Hospital, Auckland, New Zealand.
Ron HochstenbachDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Jodi D HoffmanDivision of Genetics, Department of Pediatrics, Boston Medical Center, Boston, Massachusetts, USA.
Robert J HopkinDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Monika W HubshmanPediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
A Micheil InnesDepartment of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Mira IronsAcademic Affairs, American Board of Medical Specialties, Chicago, Illinois, USA.
Melita IrvingDepartment of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Jessie C JacobsenCentre for Brain Research and School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Sandra JanssensCenter for Medical Genetics, Ghent University, Ghent, Belgium.
Tamison JewettDepartment of Pediatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
John P JohnsonDepartment of Molecular Genetics, Shodair Children's Hospital, Helena, Montana, USA.
Marjolijn C JongmansDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Stephen G KahlerDivision of Genetics and Metabolism, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
David A KoolenDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Jerome KorzeliusDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Peter M KroiselInstitute of Human Genetics, Medical University of Graz, Graz, Austria.
Yves LacassieDepartment of Pediatrics, Louisiana State University Health Sciences Center (LSUHSC) and Children's Hospital, New Orleans, Louisiana, USA.
William LawlessMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Emmanuelle LemyreDepartment of Pediatrics, University of Montreal, CHU Sainte-Justine, Montreal, Quebec, Canada.
Kathleen LeppigDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.
Alex V LevinWills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Haibo LiCenter for Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
Hong LiCenter for Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
Eric C LiaoCenter for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Cynthia LimDivision of Genetics and Metabolism, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
Edward J LoseDepartment of Genetics, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA.
Diane LucenteMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Michael J MaceraClinical Cytogenetics Laboratory, New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York, USA.
Poornima ManavalanMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Giorgia MandrileMedical Genetics Unit, Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
Carlo L MarcelisDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Lauren MargolinGenomics Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Tamara MasonGenomics Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Diane Masser-FryeDepartment of Genetics, Rady Children's Hospital, San Diego, California, USA.
Michael W McClellanDepartment of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, Washington, USA.
Cinthya J Zepeda MendozaDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Björn MentenCenter for Medical Genetics, Ghent University, Ghent, Belgium.
Sjors MiddelkampDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Liya R MikamiGroup for Advanced Molecular Investigation, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.
Emily MoeDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Shehla MohammedDepartment of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Tarja MononenDepartment of Clinical Genetics, Kuopio University Hospital, Kuopio, Finland.
Megan E MortensonDepartment of Pediatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Graciela MoyaGENOS Laboratory, Buenos Aires, Argentina.
Aggie W NieuwintDepartment of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands.
Zehra OrduluDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Sandhya ParkashMaritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia, Canada.
Susan P PaukerHarvard Medical School, Boston, Massachusetts, USA.
Shahrin PereiraDepartment of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Danielle PerrinGenomics Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Katy PhelanHayward Genetics Program, Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Raul E Piña AguilarMedical Genomics Division, Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico.
Pino J PoddigheDepartment of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands.
Giulia PregnoMedical Genetics Unit, Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
Salmo RaskinGroup for Advanced Molecular Investigation, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.
Linda ReisDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
William RheadDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Debra RitaMidwest Diagnostic Pathology, Aurora Clinical Labs, Rosemont, Illinois, USA.
Ivo RenkensDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Filip RoelensAlgemeen Ziekenhuis Delta, Roeselare, Belgium.
Jayla RulieraCenter for Human Genetic Research DNA and Tissue Culture Resource, Boston, Massachusetts, USA.
Patrick RumpUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.ORCID 0000-0003-4059-0247
Samantha L P SchilitDepartment of Genetics, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-8991-6327
Ranad ShaheenDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Rebecca SparkesDepartment of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Erica SpiegelDivision of Maternal Fetal Medicine, Columbia University Medical Center, New York, New York, USA.
Blair StevensMcGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas, USA.
Matthew R StoneMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Julia TagoeGenetic Services, Alberta Health Services, Lethbridge, Alberta, Canada.
Joseph V ThakuriaHarvard Medical School, Boston, Massachusetts, USA.
Bregje W van BonDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Jiddeke van de KampDepartment of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands.
Ineke van Der BurgtDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Ton van EssenUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Conny M van Ravenswaaij-ArtsUniversity of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Markus J van RoosmalenDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Sarah VergultCenter for Medical Genetics, Ghent University, Ghent, Belgium.ORCID 0000-0002-0816-6262
Catharina M L Volker-TouwDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Dorothy P WarburtonDivision of Clinical Genetics, Columbia University Medical Center, New York, New York, USA.
Matthew J WatermanMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Susan WileyDivision of Developmental and Behavioral Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinatti, Ohio, USA.
Anna WilsonMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Maria de la Concepcion A Yerena-de VegaLaboratory of Genetics, Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico.
Roberto T ZoriDivision of Pediatric Genetics and Metabolism, University of Florida, Gainesville, Florida, USA.
Brynn LevyDepartment of Pathology, Columbia University, New York, New York, USA.
Han G BrunnerDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Nicole de LeeuwDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Wigard P KloostermanDivision of Biomedical Genetics, Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Erik C ThorlandDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Cynthia C MortonProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0003-2198-6756
James F GusellaMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Michael E TalkowskiMolecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Broad Institute · USRadboud University Nijmegen · NLUniversity Medical Center Utrecht · NLBrigham and Women's Hospital · USMassachusetts General Hospital · USGhent University Hospital · BEChildren's Hospital of Wisconsin · USHarvard University · USAmsterdam UMC Location Vrije Universiteit Amsterdam · NLColumbia University Irving Medical Center · USDepartment of Medical Sciences · BYMayo Clinic · USUniversity Medical Center Groningen · NLArkansas Children's Hospital · USBaylor College of Medicine · USCenter for Human Genetics · USCincinnati Children's Hospital Medical Center · USInstitute for Social Security and Services for State Workers · MXKing Faisal Specialist Hospital & Research Centre · SANanjing Medical University · CN
Funding
RAPID GENE DISCOVERYP01GM061354 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI MORTON, CYNTHIA CASSON · 2001 to 2019
$24.3MClinical Diagnostic Sequencing of Structural VariationR01HD081256 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2015 to 2025
$7.2MComplex Genetic Architecture of Chromosomal Aberrations in AutismR00MH095867 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2014 to 2016
$747kComplex Genetic Architecture of Chromosomal Aberrations in AutismK99MH095867 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2012 to 2013
$186kIntegration of Emerging Technologies to Define the Spectrum of Structural Variation in Neuropsychiatric DiseaseF32MH110124 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI GLESSNER, JOSEPH · 2016 to 2017
$119kNew Computational Methods and Emerging Technologies in Prenatal Genetic DiagnosisF32HD085857 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI BRAND, HARRISON · 2016 to 2016
$60kMedical Research Council MC_PC_U127561093NICHD NIH HHS F32 HD085857NICHD NIH HHS R01 HD081256NIGMS NIH HHS P01 GM061354NIMH NIH HHS F32 MH110124NIMH NIH HHS K99 MH095867NIMH NIH HHS R00 MH095867
Abstract
Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology.
Indexed as
Chromosome AberrationsGene RearrangementGenetic Predisposition to DiseaseGenome-Wide Association StudyCongenital AbnormalitiesFemaleGenetic MarkersHumansMaleGenetic Markers
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