Www.research.manchester.ac.uk
The Genomic Landscape of Balanced Cytogenetic Abnormalities Associated with Human Congenital AnomaliesClaire Redin1,2,3, Harrison Brand1,2,3, Ryan L. Collins1,2,3,4, Tammy Kammin5, Elyse Mitchell6, Jennelle C. Hodge6,7,8, Carrie Hanscom1,2,3, Vamsee Pillalamarri1,2,3, Catarina M. Seabra1,2,3,9, Mary-Alice Abbott10, Omar A. Abdul-Rahman11, Erika Aberg12, Rhett Adley1, Sofia L. Alcaraz-Estrada13, Fowzan S. Alkuraya14, Yu An1,15, Mary-Anne Anderson16, Caroline Antolik1,2,3, Kwame Anyane-Yeboa17, Joan F. Atkin18,19, Tina Bartell20, Jonathan A. Bernstein21, Elizabeth Beyer22, Ian Blumenthal1, Ernie M.H.F. Bongers23, Eva H. Brilstra24, Chester W. Brown25,26, Hennie T. Brüggenwirth27, Bert Callewaert28, Colby Chiang1, Ken Corning29, Helen Cox30, Edwin Cuppen24, Benjamin B. Currall1,5,31, Tom Cushing32, Dezso David33, Matthew A. Deardorff34,35, Annelies Dheedene28, Marc D’Hooghe36, Bert B.A. de Vries23, Dawn L. Earl37, Heather L. Ferguson5, Heather Fisher38, David R. FitzPatrick39, Pamela Gerrol5, Daniela Giachino40, Joseph T. Glessner1,2,3, Troy Gliem6, Margo Grady41, Brett H. Graham25,26, Cristin Griffis22, Karen W. Gripp42, Andrea L. Gropman43, Andrea Hanson-Kahn44, David J. Harris45,46, Mark A. Hayden5, Rosamund Hill47, Ron Hochstenbach24, Jodi D. Hoffman48, Robert J. Hopkin49,50, Monika W. Hubshman51,52,53, A. Micheil Innes54, Mira Irons55, Melita Irving56,57, Jessie C. Jacobsen58, Sandra Janssens28, Tamison Jewett59, John P. Johnson60, Marjolijn C. Jongmans23, Stephen G. Kahler61, David A. Koolen23, Jerome Korzelius24, Peter?M.?Kroisel62, Yves Lacassie63, William Lawless1, Emmanuelle Lemyre64, Kathleen Leppig65,66, Alex V. Levin67, Haibo Li68, Hong Li68, Eric C. Liao69,70,71, Cynthia Lim61,72, Edward J. Lose73, Diane Lucente1, Michael J. Macera74, Poornima Manavalan1, Giorgia Mandrile40, Carlo L. Marcelis23, Lauren Margolin75, Tamara Mason75, Diane Masser-Frye76, Michael W. McClellan77, Cinthya J. Zepeda Mendoza5,78, Bj?rn Menten28, Sjors Middelkamp24, Liya R. Mikami79,80, Emily Moe22, Shehla Mohammed56, Tarja Mononen81, Megan E. Mortenson59,82, Graciela Moya83, Aggie W. Nieuwint84, Zehra Ordulu5,78, Sandhya Parkash12,85, Susan P. Pauker78,86, Shahrin Pereira5, Danielle Perrin75, Katy Phelan87, Raul E. Pi?a Aguilar13,88, Pino J. Poddighe84, Giulia Pregno40, Salmo Raskin79, Linda Reis89, William Rhead90, Debra Rita91, Ivo Renkens24, Filip Roelens92, Jayla Ruliera16, Patrick Rump93, Samantha L.P. Schilit30,78, Ranad Shaheen14, Rebecca Sparkes54, Erica Spiegel17, Blair Stevens94, Matthew R. Stone1,2,3, Julia Tagoe95, Joseph V. Thakuria78,96, Bregje W. van Bon23, Jiddeke van de Kamp84, Ineke van Der Burgt23, Ton van Essen93, Conny M. van Ravenswaaij-Arts93, Markus J. van Roosmalen24, Sarah Vergult28, Catharina M.L. Volker-Touw24, Dorothy P. Warburton97, Matthew J. Waterman1,98, Susan Wiley99, Anna Wilson1, Maria de la Concepcion A. Yerena-de Vega100, Roberto T. Zori101, Brynn Levy102, Han G. Brunner23,103, Nicole de Leeuw23, Wigard P. Kloosterman24, Erik C. Thorland6, Cynthia C. Morton3,5,78,104,105, James F. Gusella1,3,31, Michael E. Talkowski1,2,3,*1Molecular Neurogenetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA;2Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA; 4Program in Bioinformatics and Integrative Genomics, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA;5Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA; 6Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55902, USA;7Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;8Department of Pediatrics, University of California Los Angeles, Los Angeles, CA 90095, USA;9GABBA Program, University of Porto, Porto, Portugal;10Medical Genetics, Baystate Medical Center, Springfield, MA 01199, USA;11Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA;12Maritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia, Canada;13Medical Genomics Division, Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico;14Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia;15The Institutes of Biomedical Sciences (IBS) of Shanghai Medical School and MOE Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai, China;16Center for Human Genetic Research DNA and Tissue Culture Resource, Boston, MA 02114, USA;17Division of Clinical Genetics, Columbia University Medical Center, New York, NY 10032, USA; 18Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA; 19Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH 43205, USA20Kaiser Permanente, Genetics Department, Sacramento, CA 95815, USA;21Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA;22Children's Hospital of Wisconsin and Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA;23Department of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen 6500 HB, the Netherlands;24Department of Genetics, Division of Biomedical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands;25Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;26Department of Genetics, Texas Children's Hospital, Houston, TX 77054, USA;27Department of Clinical Genetics, Erasmus University Medical Centre, PO BOX 2040, 3000 CA Rotterdam, The Netherlands;28Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium;29Greenwood Genetic Center, Columbia, SC, 29201, USA;30West Midlands Regional Clinical Genetics Unit, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, England, UK;31Department of Genetics, Harvard Medical School, Boston, MA 02115, USA;32University of New Mexico, School of Medicine, Department of Pediatrics, Division of Pediatric Genetics, Albuquerque, NM 87131, USA;33Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, Lisbon, Portugal;34Department of Pediatrics, Perelman School of Medicine at the?University of Pennsylvania, Philadelphia, PA 19104, USA;35Division of Human Genetics,?Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA;36Department of Neurology and Child Neurology, Algemeen Ziekenhuis Sint-Jan, Brugge, Belgium;37Seattle Children’s, Seattle, Washington, WA 98105, USA;38Mount Sinai West Hospital, New York, NY 10019, USA;39Medical Research Council Human Genetics Unit, Institute of Genetic and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK;40Medical Genetics Unit, Department of Clinical and Biological Sciences, University of Torino, Italy;41UW Cancer Center at ProHealth Care, Waukesha, Wisconsin, WI 53188, USA;42Sidney Kimmel Medical School at Thomas Jefferson University, Philadelphia, PA 19107, USA;43Children's National Medical Center, Washington, DC 20010, USA;44Departments of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA;45Division of Genetics, Boston Children's Hospital, Boston, MA 02115, USA;46Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA;47Department of Neurology, Auckland City Hospital, Auckland, New Zealand;48Department of Pediatrics, Division of Genetics, Boston Medical Center, MA 02118, USA;49Cincinnati Children's Hospital Medical Center, Division of Human Genetics, Cincinnati, OH 45229, USA;50Department of Pediatrics, University of Cincinnati College Medicine, Cincinnati, OH 45267, USA;51Pediatric Genetics Unit, Schneider Children’s Medical Center of Israel, Petach Tikva 49202, Israel;52Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikva 49100, Israel;53Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;54Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada;55Academic Affairs, American Board of Medical Specialties, Chicago, IL 60654, USA;56Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK;57Division of Medical and Molecular Genetics, King's College London, UK;58Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland, New Zealand;59Department of Pediatrics, Wake Forest School of Medicine, Winston Salem, NC 27157, USA;60Shodair Children's Hospital, Molecular Genetics Department, Helena, MT 59601, USA;61Division of Genetics and Metabolism, Arkansas Children's Hospital, Little Rock, AR 72202, USA;62Institute?of?Human?Genetics, Medical?University?of?Graz, Graz, Austria;63Department of Pediatrics at Louisiana State University Health Sciences Center (LSUHSC) and Children's Hospital, New Orleans, LA 70118, USA;64Department of Pediatrics, University of Montreal, CHU Sainte-Justine, Montréal QC, Canada;65Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; 66Clinical Genetics, Group Health Cooperative, Seattle, WA 98112, USA;67Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA;68Center for Reproduction and Genetics, The affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China; 69Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;70Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA 02114, USA;71Harvard Stem Cell Institute, Cambridge, MA 02138, USA;72Virginia G. Piper Cancer Center at HonorHealth, Scottsdale, AZ 85258, USA;73Department of Genetics, University of Alabama at Birmingham (UAB), Birmingham, AL 35233, USA;74New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032,USA;75Program in Medical and Population Genetics and Genomics Platform, Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA;76Department of Genetics, Rady Children's Hospital San Diego, CA 92123, USA;77Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA 98431, USA;78Harvard Medical School, Boston, MA 02115, USA;79Group for Advanced Molecular Investigation, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil;80Centro Universitário Aut?nomo do Brasil (Unibrasil), Curitiba, Paraná,Brazil;81Department of Clinical Genetics, Kuopio University Hospital, Finland;82Novant Health Derrick L. Davis Cancer Center, Winston Salem, NC 27103, USA;83GENOS Laboratory, Buenos Aires, Argentina;84Department of Clinical Genetics, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands;85Department of Pediatrics, Maritime Medical Genetics Service, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada;86Medical Genetics, Harvard Vanguard Medical Associates, Watertown, MA 02472, USA;87Hayward Genetics Program, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA;88School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom;89Department of Pediatrics and Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA;90Children's Hospital of Wisconsin and Departments of Pediatrics and Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;91Midwest Diagnostic Pathology, Aurora Clinical Labs, Rosemont, IL 60018, USA;92Algemeen Ziekenhuis Delta, Roeselare, Belgium;93University of Groningen, University Medical Center Groningen, Department of Genetics, PO Box 30.001, 9700RB Groningen, The Netherlands;94McGovern Medical School at The University of Texas Health Science Center at Houston, TX 77030, USA;95Genetic Services, Alberta Health Services, Alberta T1J 4L5, Canada;96Division of Medical Genetics, Massachusetts General Hospital, Boston, MA 02114, USA;97Department of Clinical Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA;98Eastern Nazarene College, Department of Biology, Quincy, MA 02170, USA;99Cincinnati Children’s Hospital Medical Center, University of Cincinnati, OH 45229, USA;100Laboratory of Genetics, Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico;101Division of Pediatric Genetics & Metabolism, University of Florida, Gainesville, FL 32610, USA;102Department of Pathology, Columbia University, New York, NY10032, USA;103Department of Clinical Genetics, Maastricht University Medical Centre, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands;104Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA;105Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester Academic Health Science Center, Manchester, UK;*Correspondence should be addressed to M.E.T. (talkowski@chgr.mgh.harvard.edu)ABSTRACTDespite their clinical significance, characterization of balanced chromosomal abnormalities (BCAs) 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 revealed 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. This study proposes that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements, and provides insight into novel pathogenic mechanisms such as long-range regulation due to changes in chromosome topology.Keywords: Cytogenetics, structural variation, balanced chromosomal abnormality, congenital anomaly, intellectual disability, autism, translocation, inversion, chromothripsis, topologically associated domain (TAD), Hi-C, MEF2CBalanced chromosomal abnormalities (BCA) are a class of structural variation involving rearrangement of chromosome structure that alters the orientation or localization of a genomic segment without a concomitant large gain or loss of DNA. This class of variation includes inversions, translocations, excisions/insertions, and more complex rearrangements consisting of combinations of such events. Cytogenetic studies of unselected newborns and control adult males estimate a prevalence of 0.2-0.5% for BCAs in the general populationPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KYWNvYnM8L0F1dGhvcj48WWVhcj4xOTc0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 1-3. By contrast, an approximate five-fold increase in the prevalence of BCAs detected by karyotyping has been reported among subjects with neurodevelopmental disorders, particularly intellectual disability (1.5%) ADDIN EN.CITE <EndNote><Cite><Author>Funderburk</Author><Year>1977</Year><RecNum>1062</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>1062</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1456183052">1062</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Funderburk, S. J.</author><author>Spence, M. A.</author><author>Sparkes, R. S.</author></authors></contributors><titles><title>Mental retardation associated with "balanced" chromosome rearrangements</title><secondary-title>Am J Hum Genet</secondary-title></titles><periodical><full-title>American Journal of Human Genetics</full-title><abbr-1>Am. J. Hum. Genet.</abbr-1><abbr-2>Am J Hum Genet</abbr-2></periodical><pages>136-41</pages><volume>29</volume><number>2</number><keywords><keyword>Adolescent</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>*Chromosome Aberrations</keyword><keyword>Chromosomes/ultrastructure</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Infant, Newborn</keyword><keyword>Intellectual Disability/*genetics</keyword><keyword>Karyotyping</keyword><keyword>Male</keyword><keyword>Mental Disorders/genetics</keyword><keyword>Quinacrine</keyword><keyword>*Translocation, Genetic</keyword></keywords><dates><year>1977</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0002-9297 (Print)
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ADDIN EN.CITE.DATA 6-8. Despite their significance in human disease, the clinical detection of this unique class of rearrangements still relies upon conventional cytogenetic methods such as karyotyping that are limited to microscopic resolution (~3-10 Mb) ADDIN EN.CITE <EndNote><Cite><Author>Warburton</Author><Year>1980</Year><RecNum>1042</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>1042</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1454097103">1042</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Warburton, D.</author></authors></contributors><titles><title>Current techniques in chromosome analysis</title><secondary-title>Pediatr Clin North Am</secondary-title></titles><periodical><full-title>Pediatric Clinics of North America</full-title><abbr-1>Pediatr. Clin. North Am.</abbr-1><abbr-2>Pediatr Clin North Am</abbr-2></periodical><pages>753-69</pages><volume>27</volume><number>4</number><keywords><keyword>Bromodeoxyuridine</keyword><keyword>Chromosome Aberrations/*diagnosis</keyword><keyword>Chromosome Disorders</keyword><keyword>Chromosome Mapping</keyword><keyword>Chromosomes, Human/*analysis</keyword><keyword>Cytological Techniques</keyword><keyword>DNA/analysis</keyword><keyword>Humans</keyword><keyword>Karyotyping/methods</keyword><keyword>Sister Chromatid Exchange</keyword><keyword>Staining and Labeling/methods</keyword></keywords><dates><year>1980</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0031-3955 (Print)
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ADDIN EN.CITE.DATA 16,17. Our findings indicate that formation of BCAs involves a variety of mechanisms, that the end-result often reflects substantial complexity invisible to cytogenetic assessment, that BCAs directly disrupt genes likely to contribute to early developmental abnormalities in at least one-third of subjects, and that BCAs can cause long-range regulatory changes due to alterations to the chromosome structure. RESULTSSequencing BCAs reveals cryptic complexity We sequenced DNA from 273 subjects originating from five primary referral sites that collectively engaged over 100 clinical investigators. Subjects harbored a BCA that was detected by karyotyping and presented with varied congenital and/or developmental anomalies. Most subjects were surveyed using large-insert whole-genome sequencing (liWGS or ‘jumping libraries’; 83%), with the remainder of subjects being analyzed by standard short-insert WGS or targeted breakpoint sequencing (see Online Methods; Supplementary Table 1). Subjects were preferentially selected with confirmed de novo BCAs based on cytogenetic studies at the referring site, or with rearrangements that segregated with a phenotypic anomaly within a family (72.5% of subjects); however, inheritance information was unavailable for one or both parents in the remaining 27.5% of subjects. Subjects harboring BCAs that were inherited from an unaffected parent were excluded from this study. Of interest, 62.6% of subjects received clinical CMA screening prior to enrollment to confirm the absence of a pathogenic CNV (Table 1). Subjects presented with a spectrum of clinical features: congenital anomalies ranged from organ-specific disorders to multisystem abnormalities, as well as neurodevelopmental conditions such as intellectual disability or ASD (Table 1). While no specific phenotypes were prioritized for inclusion (Supplementary Fig. 1), neurological defects were the most common feature in the cohort (80.2% of subjects when using digitalized phenotypes from Human Phenome Ontology [HPO]PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hsZXI8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 19-23. The most complex BCA involved 57 breakpoints (Supplementary Fig. 59). When analyses were restricted to the 230 subjects for which the karyotype suggested a simple chromosomal exchange, 48 (21%) were determined to harbor complexity that was cryptic to the karyotype, emphasizing the insights that are gained from nucleotide resolution. Across all BCAs, 80.7% resolved to less than ten kilobases of total genomic imbalance, although several cases harbored large cryptic imbalances (mostly deletions) of varied impact (Fig. 1b; Supplementary Table 4). Importantly, only 12.2% had imbalances of >100 kb in this study (9.3% greater than 1 Mb), representing a significantly lower fraction than previous cytogenetic estimatesPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZSBHcmVnb3JpPC9BdXRob3I+PFllYXI+MjAwNzwvWWVh
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ADDIN EN.CITE.DATA 24. Genomic imbalances associated with BCAs were larger on average among subjects without CMA pre-screening, with 15.5% harboring imbalances >1 Mb versus 5.9% in subjects pre-screened by CMA (Fig. 1b; Supplementary Table 4). The total genomic imbalance generally increased with the number of breakpoints, though there were chromothripsis and chromoplexy events that were essentially balanced (e.g., subject NIJ19 involved 13 junctions across five chromosomes that resolved to a final genomic imbalance of only 631 bases).BCA formation is mediated by multiple molecular mechanismsExtensive mechanistic studies have been performed on breakpoints of large CNV datasets; however, the limited scale and resolution of BCA studies have precluded similar analyses for balanced rearrangements. Using precise junction sequences from 662 breakpoints, we found that nearly half displayed signatures of blunt-end ligation (45%), presumably driven by non-homologous end joining (NHEJ) (Fig. 1c). A substantial fraction (29%) involved microhomology of 2-15 bp at the breakpoint junction, indicating that template-switching coupled to DNA-replication mechanisms such as microhomology-mediated break-induced replication (MMBIR) contribute to a substantial fraction of BCAs ADDIN EN.CITE <EndNote><Cite><Author>Zhang</Author><Year>2009</Year><RecNum>1029</RecNum><DisplayText><style face="superscript">25</style></DisplayText><record><rec-number>1029</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1452806813">1029</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhang, F.</author><author>Khajavi, M.</author><author>Connolly, A. M.</author><author>Towne, C. F.</author><author>Batish, S. D.</author><author>Lupski, J. R.</author></authors></contributors><auth-address>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</auth-address><titles><title>The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans</title><secondary-title>Nat Genet</secondary-title></titles><periodical><full-title>Nature Genetics</full-title><abbr-1>Nat. Genet.</abbr-1><abbr-2>Nat Genet</abbr-2></periodical><pages>849-53</pages><volume>41</volume><number>7</number><keywords><keyword>Abnormalities, Multiple/*genetics</keyword><keyword>*DNA Replication</keyword><keyword>Evolution, Molecular</keyword><keyword>Exons</keyword><keyword>*Gene Rearrangement</keyword><keyword>Humans</keyword><keyword>Myelin Proteins/genetics</keyword><keyword>Syndrome</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1546-1718 (Electronic)
1061-4036 (Linking)</isbn><accession-num>19543269</accession-num><urls><related-urls><url>. A comparable fraction (25%) of junctions harbored micro-insertions of several basepairs, consistent with NHEJ or fork stalling and template switching (FoSTeS) mechanisms (Fig. 1c). Only nine junctions (1%) contained long stretches of homologous sequences (>100 bp) that would be consistent with homology-mediated repair. This is certainly an underestimate given the limitations of short-read sequencing to capture rearrangements localized within highly homologous sequences such as segmental duplications or microsatellites. BCA breakpoint signatures from this study were also compared to 8,943 deletion breakpoints identified in 1,092 samples from the 1000 Genomes ProjectPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYnl6b3Y8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 27. Consistent with this expectation, 67% (589/876) of breakpoints in this study disrupted a gene, and at least one gene was truncated in most BCAs (75%, 186/248), which did not deviate from random expectations (observed n=408 genes, expected n=392±20, P=0.220; Supplementary Fig. 69). The properties of the disrupted genes, however, deviated significantly from randomly breakpoints for several key features, suggesting that the pathogenic impact of BCAs in this cohort is not a consequence of their likelihood to disrupt genes but rather a reflection of the gene(s) that they alter (disrupted genes provided in Supplementary Table 5). We observed significant enrichment for disruption of genes highly intolerant to truncating mutations, as defined by two independent groups (P=0.027 for Petrovski et al., P=0.0009 for Samocha et al.; Fig. 2a)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZXRyb3Zza2k8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFy
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ADDIN EN.CITE.DATA 30, and genes previously associated with autosomal dominant disorders (P=0.002) ADDIN EN.CITE <EndNote><Cite><Author>Berg</Author><Year>2013</Year><RecNum>1036</RecNum><DisplayText><style face="superscript">31</style></DisplayText><record><rec-number>1036</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1453219937">1036</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Berg, J. S.</author><author>Adams, M.</author><author>Nassar, N.</author><author>Bizon, C.</author><author>Lee, K.</author><author>Schmitt, C. P.</author><author>Wilhelmsen, K. C.</author><author>Evans, J. P.</author></authors></contributors><auth-address>Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. jsberg@med.unc.edu</auth-address><titles><title>An informatics approach to analyzing the incidentalome</title><secondary-title>Genet Med</secondary-title></titles><periodical><full-title>Genetics in Medicine</full-title><abbr-1>Genet. Med.</abbr-1><abbr-2>Genet Med</abbr-2></periodical><pages>36-44</pages><volume>15</volume><number>1</number><keywords><keyword>Algorithms</keyword><keyword>Alleles</keyword><keyword>Databases, Genetic</keyword><keyword>Gene Frequency</keyword><keyword>Genome-Wide Association Study/*methods</keyword><keyword>Genomics/*methods</keyword><keyword>Humans</keyword><keyword>Mutation</keyword></keywords><dates><year>2013</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1530-0366 (Electronic)
1098-3600 (Linking)</isbn><accession-num>22995991</accession-num><urls><related-urls><url>, whereas no enrichment was observed for genes associated with autosomal recessive disorders (P=0.294; Fig. 2a) ADDIN EN.CITE <EndNote><Cite><Author>Berg</Author><Year>2013</Year><RecNum>1036</RecNum><DisplayText><style face="superscript">31</style></DisplayText><record><rec-number>1036</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1453219937">1036</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Berg, J. S.</author><author>Adams, M.</author><author>Nassar, N.</author><author>Bizon, C.</author><author>Lee, K.</author><author>Schmitt, C. P.</author><author>Wilhelmsen, K. C.</author><author>Evans, J. P.</author></authors></contributors><auth-address>Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. jsberg@med.unc.edu</auth-address><titles><title>An informatics approach to analyzing the incidentalome</title><secondary-title>Genet Med</secondary-title></titles><periodical><full-title>Genetics in Medicine</full-title><abbr-1>Genet. Med.</abbr-1><abbr-2>Genet Med</abbr-2></periodical><pages>36-44</pages><volume>15</volume><number>1</number><keywords><keyword>Algorithms</keyword><keyword>Alleles</keyword><keyword>Databases, Genetic</keyword><keyword>Gene Frequency</keyword><keyword>Genome-Wide Association Study/*methods</keyword><keyword>Genomics/*methods</keyword><keyword>Humans</keyword><keyword>Mutation</keyword></keywords><dates><year>2013</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1530-0366 (Electronic)
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ADDIN EN.CITE.DATA 40, truncated genes showed higher expression patterns during early developmental stages than randomly simulated datasets (Supplementary Fig. 70). By contrast, there was no significant enrichment of genes associated with schizophreniaPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gcm9tZXI8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 41,42, or gene-sets associated with complex disorders that were considered as negative controls such as type-II diabetes, cancer, or height. Indeed, subgroup analyses revealed that most enrichment signals were driven by the predominance of neurological abnormalities among the subjects (Supplementary Fig. 71). BCAs predominantly contribute to developmental anomalies by direct gene truncationWe next asked the fundamental question: “How often does a BCA represent a likely pathogenic mutation that contributes to the subject’s abnormal developmental phenotype?” We sought to interpret the clinical significance of each BCA with reference to the phenotype reported in the proband and the genomic region(s) altered. We built an interpretation framework using categories comparable to those established by ClinVar and the Deciphering Developmental Disorders consortium (DDD) ADDIN EN.CITE <EndNote><Cite><Author>Landrum</Author><Year>2016</Year><RecNum>1128</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>1128</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1470763500">1128</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Landrum, M. J.</author><author>Lee, J. M.</author><author>Benson, M.</author><author>Brown, G.</author><author>Chao, C.</author><author>Chitipiralla, S.</author><author>Gu, B.</author><author>Hart, J.</author><author>Hoffman, D.</author><author>Hoover, J.</author><author>Jang, W.</author><author>Katz, K.</author><author>Ovetsky, M.</author><author>Riley, G.</author><author>Sethi, A.</author><author>Tully, R.</author><author>Villamarin-Salomon, R.</author><author>Rubinstein, W.</author><author>Maglott, D. R.</author></authors></contributors><auth-address>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20893, USA landrum@ncbi.nlm..
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20893, USA.</auth-address><titles><title>ClinVar: public archive of interpretations of clinically relevant variants</title><secondary-title>Nucleic Acids Res</secondary-title></titles><periodical><full-title>Nucleic Acids Research</full-title><abbr-1>Nucleic Acids Res.</abbr-1><abbr-2>Nucleic Acids Res</abbr-2></periodical><pages>D862-8</pages><volume>44</volume><number>D1</number><dates><year>2016</year><pub-dates><date>Jan 4</date></pub-dates></dates><isbn>1362-4962 (Electronic)
0305-1048 (Linking)</isbn><accession-num>26582918</accession-num><urls><related-urls><url>; however, we restricted interpretation of potential clinical relevance to Pathogenic or Likely Pathogenic, as detailed below and in Supplementary Table 7. All other variants were interpreted as Variant of Unknown Significance (VUS), as we lacked sufficient data to interpret variants as Benign or Likely Benign (Supplementary Table 8).Pathogenic: We compared loci disrupted by BCAs to genes that had been robustly associated with dominant developmental disorders (≥3 reported cases with dnLoF in OMIM, DDD, and amalgamated large-scale sequencing studies in neurodevelopmental disorders; see Supplementary Note and Supplementary Table 6). In total, 66 subjects (26.6%) harbored Pathogenic BCAs that disrupted these previously defined developmental loci either through direct gene disruption or genomic imbalance (Fig. 2c; Table 2; Supplementary Table 9). In the majority of these subjects (53/66), the rearrangement truncated a high confidence syndromic locus. These included known drivers of recurrent microdeletion syndromes (e.g., SATB2, MBD5, EHMT1, NFIA, ZBTB20)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LbGVlZnN0cmE8L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFy
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ADDIN EN.CITE.DATA 44-48, loci associated with imprinting disorders (SNURF-SNRPN), and genes well-established as highly penetrant loci in developmental disorders (e.g., CHD7, CHD8, CDKL5, CUL3, DYRK1A, GRIN2B), as well as more recently implicated genes such as AHDC1, CTNND2 and WAC (Fig. 2c; Table 2; Supplementary Table 9). Several genes were disrupted in two or more subjects, further confirming their role in developmental anomalies (Table 2). Importantly, ten subjects harbored BCAs that disrupted genes associated with dominant disorders for which the expected phenotype was not observed in the proband (e.g. cardiovascular defects, childhood or late-onset hearing loss, neurodegenerative disorder; Supplementary Table 9). In these subjects for which we observed discordant genotype-phenotype correlations from expectations in the literature, the rearrangements could represent pleiotropy in which disruption of the same locus can manifest in multiple distinct phenotypes, or incidental findings, and were thus interpreted as VUS. In the remaining 13 subjects with Pathogenic BCAs (13/66), genomic imbalances at the breakpoints either overlapped with known microdeletion/microduplication syndromes, or encompassed a gene associated with a dominant developmental disorder (e.g., 12p12.1-p11.22 deletion encompassing SOX5; Table 2; Fig. 2c).Likely Pathogenic: Each specific rearrangement effectively represents a private event, or an N-of-1, which is a major challenge for interpretation in genomic studies. To interpret variants as Likely Pathogenic, we relied on convergent genomic evidence from large-scale datasets, postulating that candidate genes associated with congenital anomalies or early developmental defects would show evidence of reduced reproductive fitness and intolerance to haploinsufficiency. Thirty-one subjects harbored BCAs that were considered Likely Pathogenic (Table 2; Supplementary Tables 8, 10). In 25 subjects, the rearrangement directly disrupted a gene intolerant to dnLoF, and in which dnLoF mutations had been previously reported in isolated cases (1 or 2 subjects, with an additional subject now represented by the BCA in our study; e.g. CACNA2D3, ROBO2, NFIB), some of which had strong biological support for involvement in developmental anomalies (EP400, STXBP5, NRXN3). There were also several genes disrupted in multiple subjects from the cohort (NPAS3, PTPRZ1, SYNCRIP; Table 2, Supplementary Tables 10-11). Two subjects had BCAs likely associated with genomic disorders: one involved duplication of the 2p21-p13.3 encompassing NRXN1, and the other disrupted the imprinted 11p15 region associated with Silver-Russel syndrome (MIM#180860). In the remaining four subjects with Likely Pathogenic BCAs, the rearrangement truncated genes that were associated with developmental disorders, yet only activating or missense mutations had been previously reported (e.g., CACNA1C and GNB1)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TcGxhd3NraTwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+
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ADDIN EN.CITE.DATA 49,50, proposing a dosage sensitive model for these loci. Based on these results, we interpreted that 12.5% (31/248) of subjects harbored a BCA that likely contributed to the developmental phenotype by disrupting potentially novel candidate genes or disease mechanisms.Taken together, these data suggest that 39.1% (97/248) of subjects have a phenotype that can be at least partially explained by haploinsufficiency or dosage alteration of an individual gene or locus (Fig. 2c; Supplementary Tables 8-10). Importantly, the overall diagnostic yield was significantly higher in subsets of the group, such as among those subjects who harbored de novo or co-segregating BCAs compared to subjects for whom inheritance was unknown (Fig. 2d), or among subjects who had not been screened clinically by CMA prior to enrollment (Fig. 2e). Despite these substantial yields, the marked increase in the frequency of BCAs associated with birth defects compared to the general population still suggests that alternative mutational mechanisms, other than direct gene disruption, may account for the developmental defects in a fraction of subjects for which the BCAs were interpreted as VUS. Positional effects via disruption of long-range regulatory interactionsClusters of BCA breakpoints within intergenic regions may suggest disruption of strong regulatory elements that contribute to disease manifestation via positional effects. Alternatively, this could reflect recurrent rearrangements due to fragile sites and/or recombination hotspots. To isolate genomic regions in which an unusual number of BCA breakpoints were localized, we partitioned the genome into 1 Mb bins. Only one genomic segment, localized to 5q14.3, achieved genome-wide significance. Remarkably, this genomic segment harbored eight independent BCAs (P=8×10-9; Fig. 3a). All BCA breakpoints from the 5q14.3 cluster mapped to a region overlapping with the previously described 5q14.3 microdeletion syndrome for which almost 100 subjects have been previously reported, with MEF2C as the proposed genetic driver (Fig. 3b)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GbG9yaXM8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 51-57. However, there are reported deletions that do not encompass MEF2C (Fig. 3b), and we now report seven BCAs distal to MEF2C in subjects with comparable phenotypes to those harboring direct disruption of MEF2C, challenge the notion that direct disruption of MEF2C is a necessary cause of the syndrome. When combining data from the literature, a total of 11 subjects harbor balanced rearrangement breakpoints localized to the same 1 Mb region within 5q14.3 (Fig. 3b)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5WZXJndWx0PC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 59,60. Correspondingly, in four subjects that harbored BCA breakpoints up to 860 kb distal to MEF2C, and for which RNA from lymphoblastoid cell lines (LCLs) was available, MEF2C expression was significantly reduced compared to controls (Fig. 3d). These analyses indicate that alteration of the TAD architecture in this genomic disorder region can disrupt normal MEF2C expression. When integrated with existing data, the converging clinical features suggest that multiple distinct mutational mechanisms can result in presentation of 5q14.3 microdeletion syndrome: (1) direct disruption of MEF2C via dnLoF mutations, (2) deletions including MEF2C, and (3) long-range positional effects from deletions and BCAs that do not directly truncate MEF2C yet disrupt its normal function via alteration to the physical orientation of the TAD structure (Fig. 3c).Beyond 5q14.3, three other loci (2q33.1, 6q14.3 and 14q12) were suggestive of an accumulation of BCA breakpoints, each containing BCA breakpoints from four independent subjects, although these regions did not reach genome-wide significance (P=1x10-4; Fig. 3a). At 2q33.1, one BCA disrupted SATB2, associated with Glass syndrome and recognized as the established driver of the 2q33.1 microdeletion syndromePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWxrb3dza2k8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFy
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ADDIN EN.CITE.DATA 65,66, and were consistent with the multiple previous reports of subjects with dysregulation of FOXG1 (Supplementary Fig. 73)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZW5jYXJlbGxpPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh
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ADDIN EN.CITE.DATA 68. In one subject the BCA directly disrupted SYNCRIP, another subject harbored a breakpoint distal to SYNCRIP that was part of a cryptic 6q14.3 deletion encompassing the full gene, though the impact of the other two BCAs was unclear due to their localization to an adjacent contact domain (Supplementary Fig. 74). Finally, a systematic screen identified four additional subjects in which a TAD disruption could represent a positional effect on known syndromic loci associated with a developmental disorder that closely matched the subject's phenotype (PITX2, SLC2A1, SOX9, SRCAP; Supplementary Fig. 75-77). In two of these regions, LCLs were available from the corresponding subjects and expression of the proposed driver gene was significantly reduced when compared to controls (SLC2A1 and SRCAP, Supplementary Fig. 75 and 76).Collectively, 7.3% of subjects harbored a BCA predicted to alter long-range regulatory interactions involving an established syndromic locus with comparable phenotype, recurrently involving MEF2C, SATB2, and FOXG1, while an additional four subjects harbored a BCA that may represent long-range positional effects (two confirmed by expression studies), though our sample sizes precluded detection of a significant accumulation of breakpoints in these latter four regions. These data suggest that alterations to TAD structures likely represent a significant component of the deleterious impact of genomic rearrangements. DISCUSSIONThis characterization of BCAs at nucleotide resolution offers new insights into their mechanisms of formation, the properties connected to their rearrangement in the nucleus, and a substantial yield of potentially novel genes associated with human development. These results also emphasize that neither the mere presence of a BCA in a subject with developmental anomalies nor the number of genes it disrupts (if any) provide sufficient prognostic power, but rather that the properties of the specific genes and regions that are altered are the most informative in predicting resultant phenotypes. These data build upon recent studies on genome topology and provide further evidence that alterations to chromosome structure can lead to alternative, yet potentially predictable, pathogenic mechanisms by changing the long-range regulatory architecture of physical interactions and chromatin looping in the nucleusPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MdXBpYW5lejwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+
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ADDIN EN.CITE.DATA 59,60,65. Structural variants can indeed easily scramble DNA topology and contact domains with potentially dramatic regulatory consequences. TADs cover a substantial fraction of the genome; therefore, the vast majority of structural variation will perturb one of those domains and cannot constitute a predictive criterion for pathogenicity per se based merely on the observation of a TAD structure and potentially relevant genes in which it encompasses. However, these data propose that a conservative approach in which a TAD is recurrently disrupted beyond chance expectations, it encompasses a high confidence locus with strong phenotypic overlap between the carrier of the TAD disruption and haploinsufficiency of the locus in independent subjects, and there is a demonstrated positional effect on gene expression, may represent a first step towards highlighting putative positional effects in the human genome. There is clearly a need for sensitive and specific tools to predict such positional effects caused by long-range regulatory perturbations, and to annotate further the morbid genome with more expansive knowledge of these functional interactions. The fraction of BCAs in this study that may be associated with this pathogenic mechanism is therefore just an entrée into their likely significance as a component of the unexplained genetic contribution to human birth defects.In terms of evaluating diagnostic strategies, this study further highlights limitations of current diagnostic tools such as karyotyping or CMA in interpreting and detecting BCAsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWxrb3dza2k8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy
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ADDIN EN.CITE.DATA 10,12-15. While the capability to visualize the chromosomes and detect de novo BCAs by traditional karyotyping represented a critical leap in genetic diagnostics, as exemplified by the seminal population cytogenetic studies performed by our late co-author, Dorothy Warburton ADDIN EN.CITE <EndNote><Cite><Author>Warburton</Author><Year>1991</Year><RecNum>1040</RecNum><DisplayText><style face="superscript">69</style></DisplayText><record><rec-number>1040</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1454096915">1040</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Warburton, D.</author></authors></contributors><auth-address>Department of Genetics, Columbia University, New York, NY.</auth-address><titles><title>De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints</title><secondary-title>Am J Hum Genet</secondary-title></titles><periodical><full-title>American Journal of Human Genetics</full-title><abbr-1>Am. J. Hum. Genet.</abbr-1><abbr-2>Am J Hum Genet</abbr-2></periodical><pages>995-1013</pages><volume>49</volume><number>5</number><keywords><keyword>*Chromosome Aberrations/*diagnosis/epidemiology/genetics</keyword><keyword>*Chromosome Disorders</keyword><keyword>Female</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Karyotyping</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Outcome</keyword><keyword>Prenatal Diagnosis</keyword><keyword>Prognosis</keyword><keyword>Surveys and Questionnaires</keyword><keyword>Translocation, Genetic</keyword></keywords><dates><year>1991</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0002-9297 (Print)
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ADDIN EN.CITE.DATA 24, whole-genome sequencing in this cohort suggests that, even at the resolution of 100 kb, only about 12% of BCAs involved a genomic imbalance. If we consider only the 102 subjects for whom no CMA was previously performed, this proportion increases to 18.8% at 100 kb resolution and 17.6% at 500 kb resolution, suggesting that 81.2-82.4% of BCAs in this study would be inaccessible to most CMA platforms routinely used in clinical diagnostics. Notably, there is still benefit to an initial CMA screen, as is illustrated by the significantly lower yield of pathogenic BCAs among subjects who had been pre-screened by CMA (19-37%) compared to those who had not (41-64%; Fig. 2e), indicating that a fraction of pathogenic variation in these genomes was captured by the CMA prescreen either in relation to or independent of the BCA. These data strongly argue for the implementation of technologies capable of detecting both balanced and unbalanced genomic rearrangements. This could be achieved by using a conventional cytogenetic test followed by a reflex WGS analysis when an abnormality is detected, which we have previously demonstrated can provide access to all classes of structural variation in the human genome in a relatively rapid timeframePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWxrb3dza2k8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFy
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ADDIN EN.CITE.DATA 71,72.In conclusion, these data indicate that de novo BCAs represent a highly penetrant mutational class in human disease, and that their delineation can provide prognostic insights not available at current cytogenetic resolution. Although encouraging, this yield does not explain all of the developmental anomalies in this cohort and suggests that additional pathogenic mechanisms await discovery. A meaningful fraction may be attributable to novel genes or regulatory alterations, but additional pathogenic mechanisms remain to be explored such as recessive modes of inheritance, gene fusions, disruption of imprinted regions, enhancer adoptionPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JYm4tU2FsZW08L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA 65,73, and more complex oligogenic models. Evaluation of extremely large cohorts will be required to resolve further such mechanisms, and characterization of BCAs in control populations would benefit annotation of the morbid human genome and interpretation of the biological and clinical consequences of its structural rearrangement.METHODSMethods and any associated references are available in the online version of the paper.Note: Supplementary material is available online and contains a Supplementary Note, 12 Supplementary Tables and 77 Supplementary Figures.Data availabilityAll reported breakpoints and their clinical interpretation have been submitted to dbVar (accession number: nstd133) and ClinVar (accession numbers: SCV000320745 to SCV000320992).ACKNOWLEDGMENTSWe are infinitely grateful for the seminal work led by our co-author, Prof. Dorothy Warburton, who passed away during review of this manuscript. Dr. Warburton was a pioneer in cytogenetic research and a close colleague, mentor, and friend to so many in the cytogenetics community.?We wish to thank all subjects and families who have been enrolled in this study, as well as the countless genetic counselors and clinical geneticists who contributed to the ascertainment of subjects. This study was supported by: the National Institutes of Health (grant GM061354 to M.E.T., J.F.G., C.C.M. and E.L.; grants MH095867 and HD081256 to M.E.T.), the March of Dimes (6-FY15-255 to M.E.T.), the European Molecular Biology Organization and the Marie Curie Actions of the European Commission (fellowship EMBO ALTF-183-2015 to C.R.), the Bettencourt-Schueller Foundation (young investigator award to C.R.), the Philippe Foundation (award to C.R.), the Harvard Medical School–Portugal Program in Translational and Clinical Research and Health Information (Funda??o para a Ciência e a Tecnologia, HMSP-ICT/0016/2013 to C.C.M and D.D.), the National Science Foundation (NSF Graduate Research Fellowship DGE1144152 to S.L.P.S.), the Fund for Scientific Research – Flanders (B.C. and S.V. are respectively a FWO senior clinical investigator and a FWO postdoctoral researcher), Clinical Medicine Science and Technology Projects of Jiangsu Province (grant BL2013019 to Ha.L. and Ho.L.), the Suzhou Key Medical Center (grant Szzx201505 to Ha.L. and Ho.L.), and the Royal Society of New Zealand (Rutherford Discovery Fellowship to J.C.J.). This study was also supported by the Desmond and Ann Heathwood MGH Research Scholars award to M.E.TAUTHOR CONTRIBUTIONSM.E.T, J.F.G, C.C.M, E.T., J.C.H., W.P.K., N.dL. and H.G.B designed the study. C.R., H.B., R.L.C., V.P., I.B., C.C., J.T.G., M.R.S., M.J.vR. and W.P.K., performed computational analyses. C.H., C.M.S., R.A., M-A.An., C.A., E.C., B.B.C., J.K., W.L., P.M., L.M., T.M., D.P., J.R., M.J.W. and A.W. performed cellular, molecular or genomic experiments. T.K., E.M., J.C.H, M-A.Ab., O.A.A-R., E.A.,, S.L.A-E., F.S.A, Y.A., K.A-Y., J.F.A., T.B., J.A.B., E.B., E.M.H.F.B., E.H.B, C.W.B., H.T.B., B.C., K.C., H.C., T.C., D.D., M.A.D., A.D., M.D'H., B.B.A.dV., D.L.E., H.L.F., H.F., D.R.F., P.G., D.G., T.G., M.G., B.H.G., C.G., K.W.G., A.L.G., A.H-K., D.J.H., M.A.H., R.Hi., R.Ho., J.D.H., R.J.H., M.W.H., A.M.I., Mi.I., Me.I., J.C.J., S.J., T.J., J.P.J., M.C.J., S.G.K, D.A.K., P.M.K., Y.L., E.L., K.L., A.V.L., Ha.L., Ho.L., E.C.L., C.L., E.J.L., D.L., M.J.M., G.M., C.L.M., D.M.F., M.W.M., C.Z.M., B.M., S.M., L.R.M., E.M., S.M., T.M., M.E.M., G.M., A.N., Z.O., S.P., S.P.P., S.P., K.P., R.E.P.A., P.J.P., G.P., S.R., L.R., W.R., D.R., I.R., F.R., P.R., S.L.P.S., R.Sh., R.Sp., E.S., B.S., J.T., J.V.T., B.W.vB., J.vdK., I.vDB., T.vE., C.M.vR-A, S.V., C.M.L.V-T., D.P.W., S.W., M.C.A.Y., R.T.Z., B.L., H.G.B., N.dL., W.P.K., E.C.T. C.C.M, and J.F.G. ascertained and enrolled subjects and provided phenotypic information. C.R. and M.E.T. wrote the manuscript, which was approved by all PETING FINANCIAL INTERESTSThe authors have none to declare.FIGURE TITLES AND LEGENDSFigure 1. Characterization of BCAs detected by karyotyping at nucleotide resolutiona. Circos plot of all BCA breakpoints identified in the cohort by whole-genome sequencing ADDIN EN.CITE <EndNote><Cite><Author>Krzywinski</Author><Year>2009</Year><RecNum>1069</RecNum><DisplayText><style face="superscript">74</style></DisplayText><record><rec-number>1069</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1456772621">1069</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Krzywinski, M.</author><author>Schein, J.</author><author>Birol, I.</author><author>Connors, J.</author><author>Gascoyne, R.</author><author>Horsman, D.</author><author>Jones, S. J.</author><author>Marra, M. A.</author></authors></contributors><auth-address>Canada's Michael Smith Genome Sciences Center, Vancouver, British Columbia V5Z 4S6, Canada. martink@bcgsc.ca</auth-address><titles><title>Circos: an information aesthetic for comparative genomics</title><secondary-title>Genome Res</secondary-title></titles><periodical><full-title>Genome Research</full-title><abbr-1>Genome Res.</abbr-1><abbr-2>Genome Res</abbr-2></periodical><pages>1639-45</pages><volume>19</volume><number>9</number><keywords><keyword>Animals</keyword><keyword>Chromosome Mapping</keyword><keyword>Chromosomes, Artificial, Bacterial</keyword><keyword>Chromosomes, Human, Pair 17/genetics</keyword><keyword>Chromosomes, Human, Pair 6/genetics</keyword><keyword>Contig Mapping</keyword><keyword>Dogs</keyword><keyword>Gene Dosage/*genetics</keyword><keyword>Genome/*genetics</keyword><keyword>*Genomics</keyword><keyword>Humans</keyword><keyword>Lymphoma, Follicular/*genetics</keyword><keyword>*Software</keyword></keywords><dates><year>2009</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1549-5469 (Electronic)
1088-9051 (Linking)</isbn><accession-num>19541911</accession-num><urls><related-urls><url>. One color is used per BCA to represent all rearrangement breakpoints in each individual subject. The scatter plot on the outside ring denotes breakpoint density per 1-Mb bin across the genome, with a blue arrow displaying the largest clustering of breakpoints at 5q14.3; b. Scatter plot summarizing the overall genomic imbalance associated with fully reconstructed BCAs at varying size thresholds. Curves represent the fraction of cases with final genomic imbalances greater than the corresponding size provided. Solid lines denote the final genomic imbalances for all BCAs, and are further delineated by deletions (red) or duplications (blue). The final genomic imbalances among fully mapped BCAs is also split between cases that have been pre-screened by chromosomal microarray (CMA; dashed line) versus cases without CMA data (dotted line); c. Sequence signatures of BCA breakpoints. Histogram representing nucleotide signatures at the junction of 662 Sanger-validated breakpoints: inserted nucleotides, blunt ends, microhomology, or longer stretches of homology.Figure 2. De novo BCAs associated with congenital anomalies disrupt functionally relevant loci. a. Boxplots illustrate specific gene-set enrichments at BCA breakpoints in subjects with congenital anomalies. Each boxplot represents the expected distribution (median, first and third quartiles) based on total intersections between 100,000 sets of simulated breakpoints and a particular gene-set. Red diamonds indicate the observed intersection values. Empirical Monte-Carlo P-values are indicated; b. Venn diagram showing the detailed overlap of disrupted genes previously associated with three neurodevelopmental phenotypes (intellectual disability, ASD, and epilepsy) in amalgamated exome and CNV studies. In black: high-confidence genes (3 or more de novo LoF mutations reported), in grey: low-confidence genes (two de novo LoF mutations). c-e) Pie charts illustrating diagnostic yields associated with the overall cohort and multiple subgroups of BCAs: c. Diagnostic yield associated with all 248 mapped BCAs from subjects with congenital or developmental anomalies; d. Diagnostic yields partitioned by inheritance status (confirmed de novo, segregating with a developmental anomaly, or unknown); e. Comparison of yields associated with BCAs in which large pathogenic CNVs had been excluded by a CMA pre-screen to the yield from BCAs that had not been pre-screened by CMA.Figure 3. Recurrent disruption of long-range regulatory interactions at the 5q14.3 locus.a. Manhattan plot showing the genome-wide distribution of BCA breakpoints in the cohort across each 1-Mb bin. P-values were computed by comparing observed to expected cluster sizes after 100,000 Monte Carlo randomizations, and corrected for the number of windows interrogated. One cluster (localized to 5q14.3) achieved genome-wide significance (threshold demarcated by red line; b. Hi-C profile and contact domains at the 5q14.3 locus derived from human LCLs. Overlapping Hi-C data suggests that the topology of the MEF2C-contact domain is lost in subjects carrying BCAsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SYW88L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 17 and CTCF binding sites (green: forward, red: reverse) are indicated. Multiple pathogenic mechanisms converge on a similar syndrome: multi-genic deletions that encompass MEF2C along with one or both TAD boundaries (n=68), MEF2C-intragenic deletions (n=12) or LoF mutations, deletions that do not encompass MEF2C but overlap one TAD boundary (n=13), and BCA breakpoints distal to MEF2C (breakpoints from seven subjects reported in this study and three previously reported subjects)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5WZXJndWx0PC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 14,51,56.; c. Proposed model of the chromatin folding in the region defining a regulatory unit for MEF2C. A loop is formed anchored at bidirectional CTCF binding sites resulting in distal enhancers being bridged in close proximity to MEF2C promoter regulating MEF2C expression; d. Significantly decreased expression of MEF2C was observed in subjects harboring BCAs distal to MEF2C compared to 16 age-matched controls Individual expression values, median, first and third quartiles are indicated. Differential gene expression was tested using a Wilcoxon Mann-Whitney test following normalization to three independent genes (ACTB, GAPDH and POLR2A; DGAP131, DGAP191, DGAP222: P=0.0085, DGAP218: P=0.0160).Figure 4. Correlations between phenotypes and genes disrupted in subjects harboring pathogenic BCAs.Heatmap summarizing the correlation between disrupted genes at breakpoints of pathogenic BCAs and phenotypes reported in subjects from this study. For each gene, the phenotypes reported in the corresponding subject were digitalized using HPOPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hsZXI8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 18. One tile represents the normalized count of HPO terms belonging to each organ category reported in the subject(s). Genes clustered together when sharing similarly affected organs, from which five groups can be delineated: 1- genes associated with multiple nervous system and craniofacial abnormalities (dark blue); 2- genes connected to multiple neurological phenotypes (pink); 3- genes associated with craniofacial abnormalities and a few neurological symptoms (black); 4- genes associated with skeletal and limb abnormalities, and with limited neurological involvement (green); 5- genes without neurological involvement (light blue).TABLES Table 1. Overview of clinical phenotypes for all 273 subjectsAffected subjectsFrequencyin cohortGenderMale15958.2%Female11441.8%Co-SegregationDe novo18467.4%Unknown7527.5%Inherited, segregating145.1%array-CGH analysesNormal13950.9%VUS3211.7%Not Performed10237.4%Abdomen defects5419.8%Cardiovascular defects4115.0%Eye defects5419.8%Hearing defects5219.0%Genitourinary defects5018.3%Growth defects6423.4%Head/Neck/Craniofacial defects14051.3%Integument defects5018.3%Limb defects5720.9%Musculature defects7126.0%Neurological defects21980.2%Behavior disorders5118.7%Developmental delay15958.2%Epilepsy5118.7%Hypotonia4115.0%ASD/autistic features3111.4%High functioning ASD41.5%Respiratory defects3011.0%Skeletal defects11642.4%Clinical description was converted for all 273 subjects into standardized terms using Human Phenotype Ontology (HPO)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hsZXI8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ZT4A
ADDIN EN.CITE.DATA 18, which allowed systematic association with broad phenotypic categories for each enrolled subject.Table 2. Genes and loci disrupted by BCAs and likely associated with developmental disorders2q24.3 deletion (SCN9A); 4q34 deletion; 6q13-q14.1 deletion (PHIP)a; 6q14.1 deletion (TBX18)b; 6q22.1-22.31 deletion (GJA1); 10p15.3-p14 deletion (GATA3); 11p14.2 deletion; 12p12.1-p11.22 deletion (SOX5, PTHLH); 13q14.2 deletion; 14q12-q21.1 deletion (NFKBIA, NKX2-1)c; 18p11.32-p11.22 deletiond; 19q12-q13.11 deletion; Xq25 duplicationAHDC1; AUTS2(x2); CAMTA1; CDKL5; CHD7; CHD8; CTNND2; CUL3; DYRK1A; EFTUD2; EHMT1; FGFR1; FOXP1; FOXP2; GRIN2B; IL1RAPL1; KAT6B; KDM6A(x2); MBD5(x3); MEF2C; MTAP; MYT1L(x2); MYO6e; NALCN; NFIA; NFIX; NODAL; NOTCH2; NR2F1; NR5A1; NRXN1; NSD1; PAK3; PDE10A; PHF21A(x2)d; PHIPe; SATB2; SCN1A; SMS; SNRPN-SNURF(x3); SOX5(x2); SPAST; TCF12; TCF4; WAC; ZBTB20(x2)2p21-p13.3 duplication (NRXN1)ARIH1; BBX; CACNA2D3; CACNA1C; CADPS2f CDK6(x2); CELSR1; EP400g; GNB1; GRM1h; KCND2; MDN1; NFIB; NPAS3(x4)c,i; NRXN3; PRPF40A; PSD3j; PTPRZ1(x3)a,f; ROBO2; SHROOM4g; SPTBN1; SYNCRIP(x2)b,j; STXBP5h; UPF2; 11p15 regionFOXG1(x4)i; MEF2C(x7); PITX2; SATB2(x3)j; SLC2A1; SOX9; SRCAPPathogenicGenomic imbalances at breakpointsGene disruptionLikely PathogenicGenomic imbalances at breakpointsGene disruptionPositional effectDetails on BCA interpretation are provided in Methods and Supplementary Table 7. Genes that have been associated to dominant developmental disorders and encompassed by genomic imbalances at breakpoints are indicated in brackets; lower-scripts indicate when a gene was disrupted by a BCA in multiple subjects; upper-scripts report subjects with a BCA disrupting multiple genes/loci that may each contribute to their developmental phenotype and to distinct clinical features; a: Subject DGAP133; b: Subject DGAP317, c: subject DGAP002, d: subject DGAP316, e: subject NIJ2, f: subject DGAP168, g: subject DGAP172, h: DGPA196; i: DGAP246; j: DGAP237.REFERENCES ADDIN EN.SECTION.REFLIST 1.Jacobs, P.A., Melville, M., Ratcliffe, S., Keay, A.J. & Syme, J. A cytogenetic survey of 11,680 newborn infants. Ann. Hum. Genet. 37, 359-376 (1974).2.Nielsen, J. & Wohlert, M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum. Genet. 87, 81-83 (1991).3.Ravel, C., Berthaut, I., Bresson, J.L., Siffroi, J.P. & Genetics Commission of the French Federation of, C. Prevalence of chromosomal abnormalities in phenotypically normal and fertile adult males: large-scale survey of over 10,000 sperm donor karyotypes. Hum. Reprod. 21, 1484-1489 (2006).4.Funderburk, S.J., Spence, M.A. & Sparkes, R.S. Mental retardation associated with "balanced" chromosome rearrangements. Am. J. Hum. Genet. 29, 136-141 (1977).5.Marshall, C.R. et al. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82, 477-488 (2008).6.McKusick, V.A. & Amberger, J.S. The morbid anatomy of the human genome: chromosomal location of mutations causing disease. J. Med. Genet. 30, 1-26 (1993).7.Talkowski, M.E. et al. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell 149, 525-537 (2012).8.Weischenfeldt, J., Symmons, O., Spitz, F. & Korbel, J.O. Phenotypic impact of genomic structural variation: insights from and for human disease. Nat Rev Genet 14, 125-138 (2013).9.Warburton, D. Current techniques in chromosome analysis. Pediatr. Clin. North Am. 27, 753-769 (1980).10.Talkowski, M.E. et al. Next-generation sequencing strategies enable routine detection of balanced chromosome rearrangements for clinical diagnostics and genetic research. Am. J. Hum. Genet. 88, 469-481 (2011).11.Talkowski, M.E. et al. Clinical diagnosis by whole-genome sequencing of a prenatal sample. N. Engl. J. Med. 367, 2226-2232 (2012).12.Schluth-Bolard, C. et al. Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations. J. Med. Genet. 50, 144-150 (2013).13.Utami, K.H. et al. Detection of chromosomal breakpoints in patients with developmental delay and speech disorders. PLoS One 9, e90852 (2014).14.Vergult, S. et al. Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations. Eur. J. Hum. Genet. 22, 652-659 (2014).15.Tabet, A.C. et al. Complex nature of apparently balanced chromosomal rearrangements in patients with autism spectrum disorder. Mol. Autism 6, 19 (2015).16.Jin, F. et al. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 503, 290-294 (2013).17.Rao, S.S. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665-1680 (2014).18.Kohler, S. et al. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. Nucleic Acids Res. 42, D966-974 (2014).19.Meyerson, M. & Pellman, D. Cancer genomes evolve by pulverizing single chromosomes. Cell 144, 9-10 (2011).20.Stephens, P.J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144, 27-40 (2011).21.Kloosterman, W.P. et al. Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Hum. Mol. Genet. 20, 1916-1924 (2011).22.Chiang, C. et al. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat. Genet. 44, 390-397, S391 (2012).23.Baca, S.C. et al. Punctuated evolution of prostate cancer genomes. Cell 153, 666-677 (2013).24.De Gregori, M. et al. Cryptic deletions are a common finding in "balanced" reciprocal and complex chromosome rearrangements: a study of 59 patients. J. Med. Genet. 44, 750-762 (2007).25.Zhang, F. et al. The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans. Nat. Genet. 41, 849-853 (2009).26.Abyzov, A. et al. Analysis of deletion breakpoints from 1,092 humans reveals details of mutation mechanisms. Nat Commun 6, 7256 (2015).27.Djebali, S. et al. Landscape of transcription in human cells. Nature 489, 101-108 (2012).28.Petrovski, S., Wang, Q., Heinzen, E.L., Allen, A.S. & Goldstein, D.B. Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet 9, e1003709 (2013).29.Samocha, K.E. et al. A framework for the interpretation of de novo mutation in human disease. Nat. Genet. 46, 944-950 (2014).30.Iossifov, I. et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515, 216-221 (2014).31.Berg, J.S. et al. An informatics approach to analyzing the incidentalome. Genet. Med. 15, 36-44 (2013).32.Darnell, J.C. et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247-261 (2011).33.Ascano, M., Jr. et al. FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature 492, 382-386 (2012).34.Iossifov, I. et al. De novo gene disruptions in children on the autistic spectrum. Neuron 74, 285-299 (2012).35.O'Roak, B.J. et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485, 246-250 (2012).36.Sanders, S.J. et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485, 237-241 (2012).37.De Rubeis, S. et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515, 209-215 (2014).38.Cotney, J. et al. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat Commun 6, 6404 (2015).39.Sugathan, A. et al. CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors. Proc. Natl. Acad. Sci. U. S. A. 111, E4468-4477 (2014).40.Hawrylycz, M.J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391-399 (2012).41.Fromer, M. et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 506, 179-184 (2014).42.Purcell, S.M. et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 506, 185-190 (2014).43.Landrum, M.J. et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 44, D862-868 (2016).44.Kleefstra, T. et al. Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome. Am. J. Hum. Genet. 79, 370-377 (2006).45.Lu, W. et al. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects. PLoS Genet 3, e80 (2007).46.Rosenfeld, J.A. et al. Small deletions of SATB2 cause some of the clinical features of the 2q33.1 microdeletion syndrome. PLoS One 4, e6568 (2009).47.Talkowski, M.E. et al. Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder. Am. J. Hum. Genet. 89, 551-563 (2011).48.Rasmussen, M.B. et al. Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes. J. Med. Genet. 51, 605-613 (2014).49.Splawski, I. et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc. Natl. Acad. Sci. U. S. A. 102, 8089-8096; discussion 8086-8088 (2005).50.Petrovski, S. et al. Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures. Am. J. Hum. Genet. 98, 1001-1010 (2016).51.Floris, C. et al. Two patients with balanced translocations and autistic disorder: CSMD3 as a candidate gene for autism found in their common 8q23 breakpoint area. Eur. J. Hum. Genet. 16, 696-704 (2008).52.Cardoso, C. et al. Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion. Neurology 72, 784-792 (2009).53.Engels, H. et al. A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients. Eur. J. Hum. Genet. 17, 1592-1599 (2009).54.Le Meur, N. et al. MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations. J. Med. Genet. 47, 22-29 (2010).55.Zweier, M. et al. Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression. Hum. Mutat. 31, 722-733 (2010).56.Saitsu, H. et al. De novo 5q14.3 translocation 121.5-kb upstream of MEF2C in a patient with severe intellectual disability and early-onset epileptic encephalopathy. Am. J. Med. Genet. A 155A, 2879-2884 (2011).57.Zweier, M. & Rauch, A. TheMEF2C-Related and 5q14.3q15 Microdeletion Syndrome. Mol. Syndromol. 2, 164-170 (2012).58.Dixon, J.R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380 (2012).59.Lupianez, D.G. et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161, 1012-1025 (2015).60.Lupianez, D.G., Spielmann, M. & Mundlos, S. Breaking TADs: How Alterations of Chromatin Domains Result in Disease. Trends Genet. 32, 225-237 (2016).61.Mencarelli, M.A. et al. 14q12 Microdeletion syndrome and congenital variant of Rett syndrome. Eur. J. Med. Genet. 52, 148-152 (2009).62.Ellaway, C.J. et al. 14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype. Eur. J. Hum. Genet. 21, 522-527 (2013).63.Takagi, M. et al. A 2.0 Mb microdeletion in proximal chromosome 14q12, involving regulatory elements of FOXG1, with the coding region of FOXG1 being unaffected, results in severe developmental delay, microcephaly, and hypoplasia of the corpus callosum. Eur. J. Med. Genet. 56, 526-528 (2013).64.Perche, O. et al. Dysregulation of FOXG1 pathway in a 14q12 microdeletion case. Am. J. Med. Genet. A 161A, 3072-3077 (2013).65.Ibn-Salem, J. et al. Deletions of chromosomal regulatory boundaries are associated with congenital disease. Genome Biol. 15, 423 (2014).66.Deng, Y., Gao, L., Wang, B. & Guo, X. HPOSim: an R package for phenotypic similarity measure and enrichment analysis based on the human phenotype ontology. PLoS One 10, e0115692 (2015).67.Brunetti-Pierri, N. et al. Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment. Eur. J. Hum. Genet. 19, 102-107 (2011).68.McDermott, S.M. et al. Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction. RNA 20, 1593-1606 (2014).69.Warburton, D. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am. J. Hum. Genet. 49, 995-1013 (1991).70.Brand, H. et al. Cryptic and complex chromosomal aberrations in early-onset neuropsychiatric disorders. Am. J. Hum. Genet. 95, 454-461 (2014).71.Chaisson, M.J. et al. Resolving the complexity of the human genome using single-molecule sequencing. Nature 517, 608-611 (2015).72.Huddleston, J. et al. Reconstructing complex regions of genomes using long-read sequencing technology. Genome Res. 24, 688-696 (2014).73.Lettice, L.A. et al. Enhancer-adoption as a mechanism of human developmental disease. Hum. Mutat. 32, 1492-1499 (2011).74.Krzywinski, M. et al. Circos: an information aesthetic for comparative genomics. Genome Res. 19, 1639-1645 (2009).75.Andersson, R. et al. An atlas of active enhancers across human cell types and tissues. Nature 507, 455-461 (2014).ONLINE METHODSSubject AscertainmentSubjects were enrolled through cytogenetic reference centers including DGAP (the Developmental Genome Anatomy Project) of Brigham and Women's Hospital and Massachusetts General Hospital, Boston, MA; Mayo Clinic, Rochester, MN; University Medical Center, Utrecht, NL; Radboud University Medical Center, Nijmegen, NL. Enrollment was based on the presence of a developmental anomaly and concomitant BCA (de novo or that segregated with the abnormal phenotype) detected by karyotyping, and exclusion of clinically significant genomic copy number imbalances using chromosomal microarray analyses (SNP array or array-CGH) when possible (171/273 tested subjects; Supplementary Fig. 1). In the majority of cases the BCA was confirmed to have arisen de novo by karyotyping (184/273) or segregated with a developmental phenotype in the family (14/273). In a subset of subjects: (1) the BCA was inherited but the phenotype of the transmitting parent was not available (3/273); (2) one parent was available and did not harbor the BCA (4/273); or (3) neither parents were available for testing (68/273). An informed consent was obtained from all subjects or their legal representative for participation in the study. All studies were approved by respective Institutional Review Boards.Whole-genome sequencing using large-insert jumping librariesBlood samples were collected from all subjects and their parents when available. DNA was extracted from blood or from freshly derived LCLs. Samples were prepared using multiple sequencing methods over several years (Supplementary Table 1). 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ADDIN EN.CITE.DATA 11,76, 59 using a variant of our jumping library protocol in which we randomly shear circularized DNA, which enables longer reads (paired-end 50 bp, see Supplementary Note) and 19 using standard Illumina mate-pair protocols. All large-insert sequencing methods allowed generation of paired-end reads with median insert size of 2.5-3.5 kb as opposed to 300 bp using conventional methods. A subset of samples were prepared with standard short-insert paired-end protocols (n=12) or targeted sequencing of the breakpoints based on previous positional cloning to narrow the breakpoint regions (n=34), as previously describedPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWxrb3dza2k8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFy
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ADDIN EN.CITE.DATA 7,11,77. Of note, 87 BCAs had been initially reported in the literature, though many had not been mapped to sequence resolution (Supplementary Table 1).Digitalization and homogenization of reported phenotypesClinical description was converted for all 273 subjects into standardized terms using Human Phenotype Ontology (HPO; Supplementary Table 2)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hsZXI8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ZT4A
ADDIN EN.CITE.DATA 18. Such digitalization allowed systematic comparison of phenotypes between subjects carrying BCAs that disrupted the same gene, as well as between subjects with a disrupted gene to previously described subjects using Phenomizer HYPERLINK \l "_ENREF_4_15" \o "Kohler, 2009 #1118" PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hsZXI8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 78. HPO-sim was used to compute phenotypic similarity scores between subjects sharing the disruption of the same gene or locus compared to random expectations (Supplementary Table 11). P-values were generated as the proportion of simulated scores greater than the observed probands' score, alike described by the authors ADDIN EN.CITE <EndNote><Cite><Author>Deng</Author><Year>2015</Year><RecNum>1116</RecNum><DisplayText><style face="superscript">66</style></DisplayText><record><rec-number>1116</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1470183472">1116</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Deng, Y.</author><author>Gao, L.</author><author>Wang, B.</author><author>Guo, X.</author></authors></contributors><auth-address>School of Computer Science and Technology, Xidian University, Xi'an, People's Republic of China; Institute of Software Engineering, Xidian University, Xi'an, People's Republic of China.
School of Computer Science and Technology, Xidian University, Xi'an, People's Republic of China.</auth-address><titles><title>HPOSim: an R package for phenotypic similarity measure and enrichment analysis based on the human phenotype ontology</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PloS One</full-title><abbr-1>PLoS One</abbr-1><abbr-2>PLoS One</abbr-2></periodical><pages>e0115692</pages><volume>10</volume><number>2</number><keywords><keyword>Computational Biology</keyword><keyword>Databases, Genetic</keyword><keyword>Disease/*genetics</keyword><keyword>*Gene Ontology</keyword><keyword>Genes</keyword><keyword>Genetic Predisposition to Disease</keyword><keyword>Humans</keyword><keyword>*Phenotype</keyword><keyword>*Software</keyword></keywords><dates><year>2015</year></dates><isbn>1932-6203 (Electronic)
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ADDIN EN.CITE.DATA 18. The matrix was then z-score transformed by gene, and clustering was performed using a distance matrix of correlation coefficients and average agglomeration (Figure 4). BCA discovery pipeline and breakpoint inferenceAll computational analyses have been previously describedPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFuZDwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 70,79. In brief, reads were reverse-complemented and aligned using BWA ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>2009</Year><RecNum>1044</RecNum><DisplayText><style face="superscript">80</style></DisplayText><record><rec-number>1044</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1454508486">1044</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, H.</author><author>Durbin, R.</author></authors></contributors><auth-address>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.</auth-address><titles><title>Fast and accurate short read alignment with Burrows-Wheeler transform</title><secondary-title>Bioinformatics</secondary-title></titles><periodical><full-title>Bioinformatics</full-title><abbr-1>Bioinformatics</abbr-1><abbr-2>Bioinformatics</abbr-2></periodical><pages>1754-60</pages><volume>25</volume><number>14</number><keywords><keyword>*Algorithms</keyword><keyword>Genomics/*methods</keyword><keyword>Sequence Alignment/*methods</keyword><keyword>Sequence Analysis, DNA/methods</keyword><keyword>*Software</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1367-4811 (Electronic)
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ADDIN EN.CITE.DATA 79. When no clusters were found that matched the proposed karyotype, BAM files were agnostically analyzed and manually inspected for anomalous pairs or split reads. Breakpoints were successfully identified in 248 of 273 cases, leading to an overall breakpoint fine-mapping yield of 91%. All subsequent counts and yields were computed relative to mapped cases (n=248). For the remaining 25 unmapped cases, no breakpoints were identified in proximity to the karyotype interpretation following extensive analyses and visual inspection. For the majority of these latter unresolved cases, one or more breakpoints were interpreted by the karyotype to localize near centromeres heterochromatic regions, or within segmental duplications, which are recognized to be blind spots for short-read alignments. All large genomic imbalances predicted to be connected to BCA breakpoints following rearrangement reconstruction were confirmed to have aberrant depth of coverage using a custom R-script (CNView: ).When additional DNA was available, precise breakpoint junctions were delineated at base-pair resolution by Sanger sequencing and final breakpoints coordinates were reported; else the reported coordinates reflect the closest breakpoint estimates based on the resolution of the jumping libraries (Supplementary Table 3). A total of 82.7% (725/876) of the reported breakpoints could be tested by Sanger sequencing given DNA availability, among which 662 were confirmed yielding a minimum estimate of 91.3% (662/725) sensitivity for our mapping method.Molecular signature of BCA breakpointsAs previously describedPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGlhbmc8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGlhbmc8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 22, we processed all Sanger sequences from validated breakpoints with the BWA Smith-Waterman algorithm (modified parameters z 100 -t 3 -H -T 1) to retrieve precise breakpoint coordinates as well as infer the associated microhomology, micro-insertions or blunt end signature. This approach was sufficiently high-throughput to enable the direct comparison of BCA breakpoints with a large set of deletion breakpoints published by Abyzov et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYnl6b3Y8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 26, at the cost of not allowing concomitant microhomology and base insertions at breakpoints.Monte-Carlo randomization tests and associated statisticsA Browser Extensible Data (BED) file containing GRCh37/hg19 genomic coordinates of all 876 breakpoints detected by WGS was used as the input. One simulation consisted of generating random coordinates based on each pair of input coordinates, conserving the size of the feature as well as the intra-chromosomal distance when several breakpoints were localized to the same chromosome in a single individual. N-masked regions were excluded from simulations for consistency as they were excluded from the initial alignment mapping. Simulations were repeated 100,000 times. The number of unique intersections between the shuffled file and a BED-file containing features of interest (gene-sets, regulatory elements, etc.) was retrieved for each simulation, and the final sets of simulations delineated the expected distribution on intersections under the null hypothesis. The observed value of intersected features in this study was compared to this expected distribution. Empirical Monte-Carlo P-values were indicated, and were calculated as follows: P-value = (r + 1)/(n + 1), where r is the number of observations within the set of simulations that are at least as extreme as the one observed, and n is the total number of simulations ADDIN EN.CITE <EndNote><Cite><Author>North</Author><Year>2002</Year><RecNum>1054</RecNum><DisplayText><style face="superscript">82</style></DisplayText><record><rec-number>1054</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1455552084">1054</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>North, B. V.</author><author>Curtis, D.</author><author>Sham, P. C.</author></authors></contributors><titles><title>A note on the calculation of empirical P values from Monte Carlo procedures</title><secondary-title>Am J Hum Genet</secondary-title></titles><periodical><full-title>American Journal of Human Genetics</full-title><abbr-1>Am. J. Hum. Genet.</abbr-1><abbr-2>Am J Hum Genet</abbr-2></periodical><pages>439-41</pages><volume>71</volume><number>2</number><keywords><keyword>*Monte Carlo Method</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0002-9297 (Print)
0002-9297 (Linking)</isbn><accession-num>12111669</accession-num><urls><related-urls><url>. References for all functional element datasets and genesets that were used to test for enrichment at breakpoints in the cohort are detailed in Supplementary Table 12. To isolate genomic regions in which an unusual number of BCA breakpoints were localized, we partitioned the genome into 1 Mb bins using a sliding window of 100 kb, and counted the number of BCA breakpoints coming from independent subjects. The same approach was performed for 100,000 sets of simulated breakpoints generated as detailed previously. P-values were computed by comparing observed to expected cluster sizes after 100,000 Monte Carlo randomizations, and corrected for the total number of windows interrogated. Genome-wide significance was achieved for clusters with P-values below 1.6x10-6.BCA outcome interpretationTo build reference lists of genes associated with dominant developmental disorders we amalgamated data from multiple large-scale exome sequencing, genome sequencing, or CNV studies investigating developmental (e.g. DDD consortium) and neurodevelopmental disorders (mostly intellectual disability, autism, and epilepsy cohorts; see Supplementary Note and Supplementary Table 6 for detailed references). We then built our interpretation using standard categories comparable to those established by ClinVar and the Deciphering Developmental Disorders consortium (DDD) ADDIN EN.CITE <EndNote><Cite><Author>Landrum</Author><Year>2016</Year><RecNum>1128</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>1128</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1470763500">1128</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Landrum, M. J.</author><author>Lee, J. M.</author><author>Benson, M.</author><author>Brown, G.</author><author>Chao, C.</author><author>Chitipiralla, S.</author><author>Gu, B.</author><author>Hart, J.</author><author>Hoffman, D.</author><author>Hoover, J.</author><author>Jang, W.</author><author>Katz, K.</author><author>Ovetsky, M.</author><author>Riley, G.</author><author>Sethi, A.</author><author>Tully, R.</author><author>Villamarin-Salomon, R.</author><author>Rubinstein, W.</author><author>Maglott, D. R.</author></authors></contributors><auth-address>National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20893, USA landrum@ncbi.nlm..
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20893, USA.</auth-address><titles><title>ClinVar: public archive of interpretations of clinically relevant variants</title><secondary-title>Nucleic Acids Res</secondary-title></titles><periodical><full-title>Nucleic Acids Research</full-title><abbr-1>Nucleic Acids Res.</abbr-1><abbr-2>Nucleic Acids Res</abbr-2></periodical><pages>D862-8</pages><volume>44</volume><number>D1</number><dates><year>2016</year><pub-dates><date>Jan 4</date></pub-dates></dates><isbn>1362-4962 (Electronic)
0305-1048 (Linking)</isbn><accession-num>26582918</accession-num><urls><related-urls><url>, as detailed below and in Supplementary Table 7.Pathogenic: Confirmed Loci associated with developmental disorders. Any gene with three or more de novo LoF mutations (frameshift, nonsense or splice mutation, CNV, or BCA) reported from independent cases in those amalgamated studies or in OMIM was considered as high confidence for a particular phenotype, and any BCA impacting one of those loci was therefore considered to be Pathogenic (Supplementary Table 9). Likely Pathogenic: Novel candidate genes or mechanisms. To evaluate the impact of the remaining BCAs and the genes they likely impacted, we relied on convergent genomic evidence from other large-scale datasets to prioritize which gene would most likely contribute to the subject’s phenotype. Multiple BCAs were considered to be Likely Pathogenic, based on various evidences (Supplementary Table 10): (1) Disruption of a likely risk factor: Disruption of one copy of a gene in which one or two dnLoF mutations had been previously reported and which demonstrated significant constraint (top 10% of constrained genes)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZXRyb3Zza2k8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFy
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ADDIN EN.CITE.DATA 28,29(2) Novel mechanisms: Disruption of a gene established as associated with dominant developmental disorders yet with a distinct mutation type (e.g. activating or missense mutations while we reported LoF)(3) Disruption of long-range interactions: BCA breakpoints located in the vicinity of a gene associated with dominant developmental disorders in a subject with a consistent phenotype, and predicted to impact long-range regulatory interactions.VUS: All BCAs impacting genes not fitting in any of the above-mentioned categories were considered as VUS.Predicted disruption of contact domains by BCAsTopological associated domains (TADs) and predicted loops for lymphoblastoid cells were retrieved from Dixon et al. and Rao et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SYW88L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 17,58, and genes contained within a domain for which at least one of its insulating boundaries was disrupted by a BCA were assessed. Only genes that had been previously robustly associated with dominant developmental disorders (i.e., with dnLoF reported in three or more subjects) were considered for potential positional effects. A detailed comparison of the reported phenotypes in the corresponding subjects to phenotypes associated with disrupted genes in the literature was performed. For subjects identified with a BCA of plausible positional effect, the region was visualized using Juicebox HYPERLINK \l "_ENREF_4_20" \o "Durand, 2016 #1107" PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdXJhbmQ8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 17,58, as well as the RefSeq genes located in the region.Measuring gene expression from lymphoblastsIn subjects for whom the BCA was suspected to result in positional effects and for whom LCLs derived from blood were available, gene expression was investigated by quantitative RT-PCR. LCLs were not tested for mycoplasma contamination. Total RNA was extracted from LCLs using TRIzol? (Invitrogen) followed by RNeasy Mini Kit (Qiagen) column purification. cDNA was synthetized from 750 ng of extracted RNA using SuperScript? II Reverse Transcriptase (ThermoFisher Scientific with oligo(dT), random hexamers, and RNase inhibitor. Quantitative RT-PCR was performed for mRNA expression of genes of interest in the following subjects (MEF2C: DGAP131, DGAP191, DGAP218, DGAP222; SATB2: DGAP237; SLC2A1: DGAP170; SRCAP: DGAP134) using custom designed primers (see Supplementary Note). ACTB, GAPDH and POLR2A were each used as independent endogenous controls. Custom designed primers (0.75 μM final), cDNA (1:100 final) and nuclease-free water were added to the LightCycler? 480 SYBR Green I Master Mix (Roche) for a final 10 μL reaction volume. A LightCycler? 480 (Roche) was used for data acquisition. Values of each individual (subject or control) were obtained in triplicates of similar variance. Results of triplicates for each gene of interest were normalized against the average of the three endogenous controls (ACTB, GAPDH and POLR2A). Normalized expression levels were set in relation to eight age and sex-matched controls for the genes of interest SATB2, SLC2A1 and SRCAP, or 16 (eight males, eight females) age-matched controls for the gene of interest MEF2C, using the ΔΔCt method. Results are expressed as fold-change relative to the averaged control individuals. The significance of differential gene expression from a subject in comparison to controls was tested using a two-sided Wilcoxon Mann-Whitney test. All qRT-PCR results were independently replicated twice in the laboratory.METHODS-ONLY REFERENCES ADDIN EN.SECTION.REFLIST 7.Talkowski, M.E. et al. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell 149, 525-537 (2012).11.Talkowski, M.E. et al. Clinical diagnosis by whole-genome sequencing of a prenatal sample. N. Engl. J. Med. 367, 2226-2232 (2012).17.Rao, S.S. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665-1680 (2014).18.Kohler, S. et al. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. Nucleic Acids Res. 42, D966-974 (2014).22.Chiang, C. et al. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat. Genet. 44, 390-397, S391 (2012).26.Abyzov, A. et al. Analysis of deletion breakpoints from 1,092 humans reveals details of mutation mechanisms. Nat Commun 6, 7256 (2015).28.Petrovski, S., Wang, Q., Heinzen, E.L., Allen, A.S. & Goldstein, D.B. Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet 9, e1003709 (2013).29.Samocha, K.E. et al. A framework for the interpretation of de novo mutation in human disease. Nat. Genet. 46, 944-950 (2014).43.Landrum, M.J. et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 44, D862-868 (2016).58.Dixon, J.R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380 (2012).66.Deng, Y., Gao, L., Wang, B. & Guo, X. HPOSim: an R package for phenotypic similarity measure and enrichment analysis based on the human phenotype ontology. PLoS One 10, e0115692 (2015).70.Brand, H. et al. Cryptic and complex chromosomal aberrations in early-onset neuropsychiatric disorders. Am. J. Hum. Genet. 95, 454-461 (2014).76.Hanscom, C. & Talkowski, M. Design of large-insert jumping libraries for structural variant detection using illumina sequencing. Curr Protoc Hum Genet 80, 7 22 21-29 (2014).77.Higgins, A.W. et al. Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project. Am. J. Hum. Genet. 82, 712-722 (2008).78.Kohler, S. et al. Clinical diagnostics in human genetics with semantic similarity searches in ontologies. Am. J. Hum. Genet. 85, 457-464 (2009).79.Brand, H. et al. Paired-Duplication Signatures Mark Cryptic Inversions and Other Complex Structural Variation. Am. J. Hum. Genet. 97, 170-176 (2015).80.Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009).81.Tarasov, A., Vilella, A.J., Cuppen, E., Nijman, I.J. & Prins, P. Sambamba: fast processing of NGS alignment formats. Bioinformatics 31, 2032-2034 (2015).82.North, B.V., Curtis, D. & Sham, P.C. A note on the calculation of empirical P values from Monte Carlo procedures. Am. J. Hum. Genet. 71, 439-441 (2002).83.Durand, N.C. et al. Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom. Cell Syst 3, 99-101 (2016). ................
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