University of Edinburgh
The Genomic Landscape of Balanced Cytogenetic Abnormalities Associated with Human Developmental AnomaliesClaire Redin1,2,3, Harrison Brand1,2,3, Ryan L. Collins1,3,4, Tammy Kammin5, Elyse Mitchell6, Jennelle C. Hodge6,7, Carrie Hanscom1, Vamsee Pillalamarri1, Catarina M. Seabra1,8, Mary-Alice Abbott9, Omar Abdul-Rahman10, Erika Aberg11, Rhett Adley1, Sofia Alcaraz-Estrada12, Fowzan S. Alkuraya13, Yu An1,14, Mary-Anne Anderson15, Caroline Antolik1, Kwame Anyane-Yeboa16, Joan F. Atkin17,18, Tina Bartell19, Jonathan A. Bernstein20, Elizabeth Beyer21, Ernie M.H.F. Bongers22, Eva H. Brilstra23, Chester W. Brown24,25, Hennie T. Brüggenwirth26, Bert Callewaert27, Ken Corning28, Helen Cox29, Benjamin B. Currall1,5,30, Tom Cushing31, Dezso David32, Matthew A. Deardorff33,34, Annelies Dheedene27, Marc D’hooghe35, Bert B.A. de Vries22, Dawn L. Earl36, Heather L. Ferguson5, Heather Fisher37, David R. FitzPatrick38, Pamela Gerrol5, Daniela Giachino39, Joseph T. Glessner1,2,3, Troy Gliem6, Margo Grady40, Brett H. Graham41,42, Cristin Griffis21, Karen W. Gripp43, Andrea L. Gropman44, Andrea Hanson-Kahn45, David J. Harris46,47, Mark Hayden5, Ron Hochstenbach23, Jodi D. Hoffman48, Monika W. Hubshman49, A. Micheil Innes50, Mira Irons51, Melita Irving52,53, Sandra Janssens27, Tamison Jewett54, John P. Johnson55, Marjolijn C. Jongmans22, Stephen G. Kahler56, David A. Koolen22, Peter?M.?Kroisel57, Yves Lacassie58, William Lawless1, Emmanuelle Lemyre59, Kathleen Leppig60,61, Alex V. Levin62, Haibo Li63, Hong Li63, Eric C. Liao64,65,66, Cynthia Lim67,68, Edward J. Lose69, Diane Lucente1, Michael J. Macera70, Poornima Manavalan1, Giorgia Mandrile39, Carlo L. Marcelis22, Tamaron Mason71, Lauren Margolin71, Diane Masser-Frye72, Michael W. McClellan73, Bj?rn Menten27, Liya R. Mikami74,75, Emily Moe21, Shehla Mohammed76, Tarja Mononen77, Megan E. Mortenson78,79, Graciela Moya80, Aggie Nieuwint81, Zehra Ordulu5,82, Sandhya Parkash83, Susan P. Pauker84, Shahrin Pereira5, Danielle Perrin71, Katy Phelan85, Raul E. Pi?a Aguilar12,86, Pino J. Poddighe81, Giulia Pregno39, Salmo Raskin74, Linda Reis87, William Rhead88, Debra Rita89, Ivo Renkens23, Filip Roelens90, Jayla Ruliera15, Patrick Rump91, Samantha L.P. Schilit92, Ranad Shaheen13, Rebecca Sparkes93,94, Erica Spiegel95, Blair Stevens96, Matthew R. Stone1, Julia Tagoe97, Joseph V. Thakuria30,98, Bregje W. van Bon22, Jiddeke van de Kamp81, Ton van Essen91, Conny M. van Ravenswaaij-Arts91, Markus J. van Roosmalen23, Sarah Vergult27, Catharina M.L. Volker-Touw23, Dorothy P. Warburton99, Matthew J. Waterman1, Susan Wiley100,101, Anna Wilson1, Maria de la Concepcion A. Yerena-de Vega102, Roberto T. Zori103, Brynn Levy104, Han G. Brunner22,105, Nicole de Leeuw22, Wigard P. Kloosterman23, Erik C. Thorland6, Cynthia C. Morton3,5,106,107, James F. Gusella1,2,3,92, Michael E. Talkowski1,2,3,*1Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA;2Department 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, and Departments of Neurology and Genetics, Harvard Medical School, Boston, MA 02115, USA5Department of Obstetrics, Gynecology, and Reproductive Biology, 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;8GABBA Program, University of Porto, Porto, Portugal;9Medical genetics, Baystate Medical Genetics, and Baystate Children’s Subspecialty Center, Springfield, MA 01199, USA;10Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS11Maritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia, Canada12Medical Genomics Division, Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico13King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia;14Institutes of Biomedical Sciences and MOE Key Laboratory of Contemporary Anthropology,Fudan University, Shanghai, China15Center for Human Genetic Research DNA and Tissue Culture Resource, Boston, MA 02114, USA;16Columbia University Medical Center, New York, NY,10032, USA; 17Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA; 18Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH 43205, USA19Sacramento Medical Center, Department of Genetics, Sacramento, CA 95815, USA;20Department of Pediatrics, Stanford University School of Medicine, CA, USA21Children's Hospital of Wisconsin and Departments of Pediatrics, Medical College of Wisconsin.22Department of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500 HB, the Netherlands;23Department of Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands;24Department of Molecular and Human Genetics, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA;25Texas Children's Hospital, 6621 Fannin, Houston, TX 77030, USA;26Department of Clinical Genetics, Erasmus University Medical Centre, 3000 CA Rotterdam, The Netherlands;27Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium;28Greenwood Genetic Center, Columbia, SC, 29201, USA;29West midlands regional clinical genetics Unit, Birmingham Womens Hospital, Edgbaston, Birmingham B15 2TG, England, UK;30Department of Genetics, Harvard Medical School, Boston, MA, USA;31University of New Mexico, School of medicine, Department of pediatrics, Division of pediatric genetics, Albuquerque, NM 87131, USA;32Department of Human Genetics, Organization National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal33Department of Pediatrics, Perelman School of Medicine at the?University of Pennsylvania, Philadelphia, PA 19104, USA;34Division of Human Genetics,?Children's Hospital of Philadelphia, Philadelphia, PA, USA;35Algemeen Ziekenhuis Sint-Jan, Brugge, Belgium;36Seattle Children’s, Seattle, Washington, WA 98105, USA;37Mount Sinai West Hospital, New York, NY 10019, USA;38Medical Research Council Human Genetics Unit, Institute of Genetic and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK;39Medical Genetics Unit, Department of Clinical and Biological Sciences, University of Torino, Italy40UW Cancer Center at ProHealth Care, Waukesha, Wisconsin, USA41Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; 42Department of Genetics, Texas Children's Hospital, Houston, TX 77054, USA;43Sidney Kimmel Medical School at T. Jefferson University, Philadelphia, PA, USA;44Children's National Medical Center, N.W. Washington, D.C, USA45Department of Pediatrics and Genetics, Stanford University School of Medicine, CA, USA 46Division of Genetics, Boston Children's Hospital, Boston, MA, USA;47Department of Pediatrics, Harvard Medical School, Boston, MA, USA;48Department of Pediatrics, Division of Genetics, Boston Medical Center, MA, USA;49Schneider Medical Centre, Genetics, Israel;50Department of Medical Genetics and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T3B 6A8, Canada;51Academic Affairs, American Board of Medical Specialties, Chicago, IL 60654, USA;52Guy's and St Thomas' NHS Foundation Trust London, UK;53Honorary Reader, Division of Medical and Molecular Genetics, King's College London, London, UK54Wake Forest Baptist Medical Center, Winston Salem, NC 27157, USA;55Shodair Children's Hospital, Molecular Genetics Department, Helena, MT, USA;56Division of Genetics and Metabolism, Arkansas Children's Hospital, AR, USA;57Institute?of?Human?Genetics, Medical?University?of?Graz, Graz, Austria;58Department of Pediatrics LSUHSC and Children's Hospital, New Orleans, LA, USA;59CHU Sainte-Justine, 3175 chemin de la C?te-Sainte-Catherine, Montréal QC, Canada;60Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA; 61Clinical Genetics, Group Health Cooperative, Seattle, Washington, USA;62Wills Eye Hospital, Ste. 1210, 840 Walnut Street, Philadelphia, PA, USA;63Center for Reproduction and Genetics, The affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China; 64Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;65Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA 02114, USA;66Harvard Stem Cell Institute, Cambridge, MA 0213867HonorHealth/Virginia G. Piper Cancer Center, Scottsdale, AZ 85258, USA;68Arkansas Children’s Hospital, Little Rock, AR 72202, USA;69Department of Medical Genetics, University of Alabama Hospital at Birmingham, Birmingham, AL, USA;70New York-Presbyterian Hospital, Columbia University Medical Center, New York, USA;71Program in Medical and Population Genetics and Genomics Platform, Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA.72Department of Genetics, Rady Children's Hospital San Diego, CA, USA;73 Department of Obstetrics & Gynaecology, Madigan Army Medical Center, Tacoma, WA 98431, USA;74Group for Advanced Molecular Investigation, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil;75Centro Universitário Aut?nomo do Brasil (Unibrasil), Curitiba, Paraná,Brazil;76Guy's Hospital, London 77Department of Clinical Genetics, Kuopio University Hospital, Finland;78Wake Forest Baptist Medical Center, Winston Salem, NC 27157, USA;79Novant Health Derrick L. Davis Cancer Center, Winston Salem, NC 27103, USA;80GENOS Laboratory, Buenos Aires, Argentina;81Department of Clinical Genetics, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands;82Harvard Medical School, Boston, MA, USA;83Department of Pediatrics, Maritime Medical Genetics Service, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada;84Medical Genetics, Harvard Vanguard Medical Associates, 485 Arsenal St. Watertown, MA 02472, USA;85Hayward Genetics Program, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, USA;86School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom87Department of Pediatrics and Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226 USA88Children's Hospital of Wisconsin and Departments of Pediatrics and Pathology, Medical College of Wisconsin.89Midwest Diagnostic Pathology, Aurora Clinical Labs, Rosemont, IL, USA;90Algemeen Ziekenhuis Delta, Roeselare, Belgium;91University of Groningen, University Medical Center Groningen, Department of Genetics, PO Box 30.001, 9700RB Groningen, The Netherlands;92Department of Genetics, Harvard Medical School, Boston, MA, USA;93Department of Medical Genetics and Paediatrics, Cumming School of Medicine, University of Calgary, AB, Canada;94Alberta Children's Hospital, Alberta Health Services, Calgary, AB, Canada;95Columbia University Medical Center, New York, NY 10032, USA;96University of Texas Medical School at Houston, Houston, TX, USA;97Genetic Services, Alberta Health Services, Alberta, Canada T1J 4L598Division of Medical Genetics, Massachusetts General Hospital, Boston, MA 02114;99Department of Clinical Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA;100Cincinnati Children’s Hospital Medical Center, Division of Developmental at University of Cincinnati, OH, USA;101Cincinnati Children’s Hospital Medical Center, Division of Behavioral Pediatrics at University of Cincinnati, OH, USA;102Laboratory of Genetics, Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico.103Division of Pediatric Genetics & Metabolism, University of Florida, Florida, USA;104Department of Pathology, Columbia University, New York, NY, USA;105Department of Clinical Genetics, Maastricht University Medical Centre, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands;106Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA;107University of Manchester, Manchester Academic Health Science Center, Manchester, UK;*Correspondence:Michael E. Talkowski, Ph.D.Associate Professor of Neurology, Psychiatry, and PathologyCenter for Human Genetic ResearchMassachusetts General Hospital, Harvard Medical School, Broad Institute185 Cambridge St., Boston, MA 02114talkowski@chgr.mgh.harvard.edu; talkowsk@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 congenital or developmental 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% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 4% were associated with pathogenic genomic imbalances, and at least 9% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, 8 subjects harbored BCA breakpoints that localized to a single TAD encompassing MEF2C, a known driver of the 5q14.3 microdeletion syndrome, resulting in altered MEF2C expression by positional effect. 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 regulatory changes in chromosome topology. Keywords: Cytogenetics, structural variation, balanced chromosomal abnormality, congenital anomaly, intellectual disability, autism, translocation, inversion, chromothripsis, topologically associated domain (TAD), MEF2CBalanced chromosomal abnormalities (BCA) are a class of structural variation that involve rearrangement of the chromosome structure and results in a change in the orientation or localization of a genomic segment without a large concomitant 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 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 6,7. Despite their significance in human disease, the clinical detection of this unique class of chromosomal rearrangements still relies upon conventional cytogenetic methods such as karyotyping that are limited to microscopic resolution (~3-10 Mb, depending on the chromosome banding pattern and specimen type) ADDIN EN.CITE <EndNote><Cite><Author>Warburton</Author><Year>1980</Year><RecNum>1042</RecNum><DisplayText><style face="superscript">8</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 17,18. Our findings indicate that formation of BCAs involves a variety of mechanisms and sequence characteristics, that the end-result often reflects substantial complexity invisible to cytogenetic assessment, that BCAs directly disrupt genes likely to contribute to the developmental defect in approximately one-third of subjects, and that the developmental anomaly can be caused by long-range regulatory changes due to alterations to the chromosome structure. These results highlight the myriad genomic features of BCAs that have been largely unexplored in conventional cytogenetic research and demonstrate mechanisms by which they contribute to human developmental defects. RESULTSSequencing BCAs reveals cryptic complexity This study sequenced 273 subjects across five primary referral sites that collectively represented an international consortium of over 100 clinical investigators. Subjects harbored a BCA that was detected by karyotyping and presented with various congenital anomalies and other developmental defects. Most of the 273 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 S1). Subjects were preferentially selected with confirmed de novo BCAs based on cytogenetic studies at the referring site or rearrangements that segregated with a phenotypic anomaly within a family (72.5% of subjects); however, inheritance information was not available for one or both parents in the remaining 27.5% of subjects. No subjects were included if a BCA was confirmed to be inherited from an unaffected parent. 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 autism spectrum disorder (ASD; Table 1). While no specific phenotypes were prioritized for inclusion (see Supplementary Figure S1), neurological defects were the most common feature in the cohort (80% of subjects when using digitalized phenotypes from the Human Phenome Ontology [HPO] PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hsZXI8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 19; Table 1; Supplementary Table S2). Breakpoints were successfully identified in 248 of the 273 cases (90.8%); all subsequent analyses were restricted to these 248 subjects (Fig. 1). This success rate was consistent with expectations, as simulation of one million random breakpoints in the genome and comparison against all uniquely alignable 10 bp – 100 bp kmers suggests that 7.6% of simulated breakpoints were localized within N-masked regions or genomic segments that cannot be confidently mapped by short-read sequencing (Supplementary Fig. S2). Sequencing identified 874 breakpoints genome-wide and revised the breakpoint localization by at least one sub-band in 93% of subjects when compared to the karyotype interpretation (Fig. 1a; breakpoint positions provided in Supplementary Table S3). Across all rearrangements, 26% of BCAs were revealed to be complex (i.e., involved three or more breakpoints), including 5.3% that were consistent with the phenomena of chromothripsis or chromoplexy that we and others have previously defined in cancer genomes and the human germline (complex reassembly of the chromosomes involving extensive shattering and random ligation of fragments from one or more chromosomes)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWNhPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 20-24. The most complex BCA involved 57 breakpoints (Supplementary Fig. S3). When analyses were restricted to the 230 subjects for which the karyotype suggested a simple chromosomal exchange, 48 (21%) were revealed to be rearrangements with complexity that was cryptic to the karyotype, emphasizing the insights that are gained from nucleotide resolution. Across all BCAs, 81% 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 S4). Importantly, 8.8% BCAs displayed an overall genomic imbalance greater than 1 Mb and 12.2% had imbalances of >100 kb in this study, representing a significantly lower fraction than previous cytogenetic estimatesPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZSBHcmVnb3JpPC9BdXRob3I+PFllYXI+MjAwNzwvWWVh
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ADDIN EN.CITE.DATA 25. The overall genomic imbalance associated with a BCA was larger among cases without CMA pre-screening, and 13.6%/18.2% of these subjects harbored imbalances greater than 1 Mb/100 kb, respectively (Fig. 1b, Supplementary Table S4). The overall genomic imbalance also generally increased with the number of breakpoints, although a few chromothripsis and chromoplexy events were practically 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 661 breakpoints, we found that nearly half displayed signatures of blunt-end ligation (45%), presumably driven by non-homologous end joining (NHEJ) (Fig. 1c) ADDIN EN.CITE <EndNote><Cite><Author>Weischenfeldt</Author><Year>2013</Year><RecNum>971</RecNum><DisplayText><style face="superscript">7</style></DisplayText><record><rec-number>971</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1447704583">971</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Weischenfeldt, J.</author><author>Symmons, O.</author><author>Spitz, F.</author><author>Korbel, J. O.</author></authors></contributors><auth-address>Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, 69117, Germany.</auth-address><titles><title>Phenotypic impact of genomic structural variation: insights from and for human disease</title><secondary-title>Nat Rev Genet</secondary-title></titles><periodical><full-title>Nat Rev Genet</full-title></periodical><pages>125-38</pages><volume>14</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Computational Biology</keyword><keyword>Disease/*genetics</keyword><keyword>Disease Models, Animal</keyword><keyword>Epistasis, Genetic</keyword><keyword>Gene Dosage</keyword><keyword>Gene Regulatory Networks</keyword><keyword>*Genetic Association Studies</keyword><keyword>Genetic Diseases, Inborn/genetics</keyword><keyword>*Genomic Structural Variation</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Models, Genetic</keyword><keyword>RNA, Messenger/genetics/metabolism</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1471-0064 (Electronic)
1471-0056 (Linking)</isbn><accession-num>23329113</accession-num><urls><related-urls><url>. A substantial fraction (29%) involved microhomology of 2-15 bp at the junction point (median: 3-bp microhomology), 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">26</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 (1 to 375 inserted bases, median: 6-bp), consistent with NHEJ or fork stalling and template switching (FoSTeS) mechanisms (Fig. 1c). Finally, only nine junctions (1%) contained long stretches of homologous sequences (>100 bp) that would be consistent with homology-mediated repair. It is however important to note that this is almost 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 breakpoints harbored significantly different signatures when compared to CNV breakpoints, particularly deletions, suggesting that they arise from distinct mechanisms. BCA breakpoints were enriched for blunt-ends signatures while depleted for microhomology and large homology sequences (Supplementary Fig. S4), consistent with a higher implication of parison of the observed breakpoints to 100,000 independent sets of simulated breakpoints that retained the properties of the observed dataset (see Online Methods) established nominal enrichment for repeat elements (P=0.015) and fragile sites (P=0.043), while no significant enrichment for the other genomic features tested (recombination hotspots, DNAse-I hypersensitive sites, or transcription factor binding sites; Supplementary Fig. S5). When incorporating Hi-C interaction dataPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SYW88L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 27. Consistent with this expectation, 67% (596/874) of all 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 RefSeq genes, expected n=392±20, P=0.220; Supplementary Fig. S7). While BCA breakpoints were not enriched for gene disruptions beyond expectations, the properties of the disrupted genes deviated significantly from randomly simulated breakpoints for several key features, suggesting that the pathogenic impact of BCAs are not a consequence of their likelihood to disrupt genes but rather a reflection of the gene(s) that they alter. We observed a significant enrichment for disruption of genes highly intolerant to truncating mutations, as defined by two independent groups (P=0.027 and P=0.001 for Residual Variation Intolerance Score [RVIS] and probability of loss-of-function [LoF] intolerance [pLI] scores, respectively; 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) were also more likely to be disrupted than expected by chance, 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)
1098-3600 (Linking)</isbn><accession-num>22995991</accession-num><urls><related-urls><url>. The strongest enrichment at breakpoints was detected for genes previously associated with developmental disorders (≥2 de novo LoF mutations [dnLoF]) as amalgamated from multiple independent datasets (P=2x10-5; see Supplementary Methods for references). Significant enrichment was also observed at breakpoints for FMRP-target genesPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYXJuZWxsPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA 32,33 and chromatin remodeling genes, replicating the enrichment observed for genes with dnLoF in subjects with neurodevelopmental disorders (Fig. 2b)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZSBSdWJlaXM8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA 39,40, or gene-sets associated with complex disorders that were considered as negative controls such as type-II diabetes, cancer, or height. Given the uneven distribution of clinical phenotypes in the cohort, we anticipated that some of those enrichment signals could be biased by the enriched ascertainment of subjects with neurological conditions. We therefore performed analyses that segregated subjects with or without nervous system related conditions using HPO-reported phenotypes, and replicated most associations for the subset of cases with neurological conditions while most enrichments were not significant for the smaller subset of subjects with no nervous system abnormalities reported (Supplementary Fig. S9). 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 proband and the genomic region(s) altered by the rearrangement. We built our interpretation using categories comparable to those established by ClinVar ADDIN EN.CITE <EndNote><Cite><Author>Landrum</Author><Year>2016</Year><RecNum>1128</RecNum><DisplayText><style face="superscript">41</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 variants of potential clinical relevance to Pathogenic or Likely Pathogenic, as detailed below. All other variants were interpreted as Variant of Unknown Significance (VUS), as we lacked clinical or functional support to claim variants as Benign or Likely Benign. 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, the Deciphering Developmental Disorders consortium [DDD], and amalgamated large-scale sequencing studies in neurodevelopmental disorders; see Supplementary Methods for references; Supplementary Table S5). In total, 65 subjects (26%) harbored Pathogenic BCAs that incriminated these previously defined developmental loci either through direct gene disruption or genomic imbalances (Fig. 2c). In the vast majority of these subjects (53/65; 82%), 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+PEF1dGhvcj5UYWxrb3dza2k8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy
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ADDIN EN.CITE.DATA 42-46, loci associated with imprinted disorders (SNURF-SNRPN), and genes well-established as highly penetrant loci in developmental disorders (e.g., CHD8, CDKL5, CUL3, DYRK1A, GRIN2B), as well as more recently described genes such as AHDC1, CTNND2, and WAC (Fig. 2c; Table 2; Supplementary Tables S5-7). Several genes were disrupted in two or more subjects in this cohort, further confirming their significant role in developmental anomalies: AUTS2, KDM6A, MBD5, MYO6, MYT1L, PHF21A, PHIP, SNURF-SNRPN, SOX5 and ZBTB20 (Fig. 2c; Supplementary Tables S5-7 and S9). Importantly, 9 subjects harbored BCA that disrupted genes associated with dominant disorders for which the expected phenotype (e.g. cardiovascular defects) did not match with the one reported in the proband. In the remaining twelve subjects with Pathogenic BCAs (12/65; 18%), genomic imbalances at the breakpoints either overlapped with known microdeletions/microduplications syndromes, or encompassed a gene associated with a dominant developmental disorder (e.g. 12p12.1-p11.22 deletion encompassing SOX5; 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 when the BCA did not disrupt established developmental loci, we relied on convergent genomic evidence from large-scale datasets. The assumption was that candidate genes associated with congenital anomalies or early developmental defects would show evidence of reduced reproductive fitness and intolerance to haploinsufficiency. Twenty-eight subjects harbored BCAs that were considered as likely pathogenic (Supplementary Tables S6, S8). In 23 subjects, the rearrangement directly disrupted a gene highly intolerant to dnLoF, and in which dnLoF mutations had been previously reported in isolated cases (2 or fewer subjects, with an additional subjects now represented by the BCA in our study; e.g. CACNA2D3, ROBO2, NFIB) and had strong biological support for involvement in developmental anomalies (EP400, STXBP5, NRXN3). Among those proposed candidate genes, several were disrupted in multiple subjects from the cohort (NPAS3x4, PTPRZ1x3, SYNCRIPx2, SENP6x2; Supplementary Tables S5-6 and S8-9). In the remaining five subjects with Likely Pathogenic BCAs, the rearrangement truncated genes that were established developmental disorders yet in which only activating mutations had been previously reported (NOTCH2, CACNA1C and GNB1)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZXRyb3Zza2k8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFy
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ADDIN EN.CITE.DATA 47-49, proposing a dosage sensitive model for these loci, comparable to recurrent genomic disorders. Based on these results, we interpreted that 11.3% (28/248) of subjects harbored a BCA that was likely contributing to the phenotype through the involvement of potentially novel candidate genes or mutational mechanisms.Collectively, these data suggest that 37.1% (92/248) of subjects from the cohort harbored a phenotype that can be at least partially explained by haploinsufficiency or increased dosage of an individual gene or locus disrupted by a BCA (Fig. 2c; Supplementary Tables S6-8). Importantly, the overall diagnostic yield was significantly higher in subsets of the cohort, such as among subjects who harbored confirmed de novo or co-segregating BCAs compared to subjects for which inheritance was unknown (Fig. 2d), or among subjects that 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 suggests that additional pathogenic mechanisms beyond direct gene disruption are likely to account for a subset of the remaining 155 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 using a sliding window of 10 kb. Only one genomic segment, consisting of several contiguous genomic bins, achieved genome-wide significance (P=8×10-9; Fig. 3a). This segment localized to cytogenetic band 5q14.3 and involved breakpoints from a remarkable eight independent BCAs. Of these eight BCAs, one directly disrupted MEF2C at 5q14.3 while the other seven BCAs mapped to intergenic regions proximal and distal to MEF2C. Importantly, among the latter 7 BCAs with intergenic disruption of 5q14.3, none included a breakpoint disrupting a locus of known significance elsewhere in the genome, suggesting that an alternative mechanism to direct gene disruption was operating in the 5q14.3 region. All BCA breakpoints from the 5q14.3 cluster overlapped with the previously described 5q14.3 microdeletion syndrome for which over 100 subjects have been previously reported, with MEF2C as the proposed driver locus for the syndromic phenotypes observed (Fig. 3b)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXJkb3NvPC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48
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ADDIN EN.CITE.DATA 50-56. However, there were deletions reported in cases that were in proximity to MEF2C but did not encompass this gene, and the presence of seven BCAs distal to MEF2C in this study challenged the hypothesis that direct disruption of MEF2C is a necessary and sufficient cause of the syndrome. When combining three previously described subjects with reported BCAs distal to MEF2C with the eight subjects from our cohort, we thus totaled eleven subjects with BCA breakpoints localized to the same 1 Mb region within 5q14.3PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GbG9yaXM8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 58,59. Correspondingly, in the four subjects that harbored BCA breakpoints up to 860 kb distal to MEF2C for which RNA from lymphoblastoid cell lines (LCLs) were available, analysis of MEF2C expression revealed a significant reduction in all four subjects compared to 16 age-matched controls divided equally by gender (Fig. 3d). These analyses provide compelling evidence that alteration of the TAD architecture encompassing this genomic disorder can inhibit normal MEF2C expression. When integrated with existing data, the converging clinical features suggest multiple distinct mutational mechanisms resulting in 5q14.3 microdeletion syndrome: (1) direct disruption of MEF2C via dnLoF mutations, (2) deletions, and (3) long-rage positional effect via alteration to the physical orientation of the TAD structure (Fig. 3c). Beyond 5q14.3, we also identified three other loci (2q33.1, 6q14.3, and 14q12) suggestive of an accumulation of BCA breakpoints, although these loci did not reach genome-wide significance (P=1x10-4). Each segment contained BCA breakpoints from four independent subjects and overlapped with known microdeletion syndromes (Figure 3a). At 2q33.1, one BCA disrupted SATB2, associated with Glass syndrome and established driver of the 2q33.1 microdeletion syndrome PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb3NlbmZlbGQ8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy
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ADDIN EN.CITE.DATA 44,12, while the remaining three rearrangements were predicted to impact long-range interactions between SATB2 and its regulatory elements, similar to the effect observed with MEF2C at 5q14.3 (Supplementary Figure S11). In the 14q12 cluster, all BCA breakpoints were distal of FOXG1, which has been reported in atypical Rett syndromePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZXJjaGU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 64 reported terms (HPO-sim P-value=0.006; see Methods and Supplementary Table S8) ADDIN EN.CITE <EndNote><Cite><Author>Deng</Author><Year>2015</Year><RecNum>1116</RecNum><DisplayText><style face="superscript">65</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 66. In one subject the BCA directly disrupted SYNCRIP, while 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 Figure S12). Finally, a systematic screen identified ten 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 (ANKH, NDP, NOTCH2, NRXN1, PITX2, SLC2A1, SOX9, SRCAP, SYN1, ZEB2; Supplementary Figure S13-15). In two of these regions, LCLs were available from the corresponding subjects and expression of the proposed driver gene was found to be significantly reduced when compared to a 16-samples control panel (SLC2A1 and SRCAP, Supplementary Figures S13 and S14). Collectively, 9.7% of subjects harbored a BCA that was predicted to alter long-range regulatory interactions involving an established syndromic locus with comparable phenotype, recurrently involving MEF2Cx7, SATB2x3, and FOXG1x4. These data suggest that alterations to TAD structures likely represent a significant component of deleterious mutations associated with genomic rearrangements. DISCUSSIONThis characterization of apparently balanced chromosomal rearrangements 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 nor the number of genes they disrupt (if any) provide substantial prognostic power, but rather that the properties of the specific genes and regions that they alter are 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+PEF1dGhvcj5JYm4tU2FsZW08L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA 64,58,59. The yield of clinically meaningful results in this study, which ranged from 26% to 46% of the subjects evaluated, suggests that there are alternative pathogenic mechanisms associated with de novo chromosomal rearrangements that warrant further exploration. These data provide an initial vantage of the potential utility of emerging datasets that characterize the nuclear organization of the chromosomes. They propose novel pathogenic mechanisms by which BCAs may operate, which appear to be a consequence of the disruption of long-range interactions between regulatory elements and their target genePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JYm4tU2FsZW08L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA 64,58,59. 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. These data propose that the recurrent disruption of a TAD encompassing a high confidence locus beyond what is expected by chance, concomitant with strong phenotypic overlap between the carrier of the variant and haploinsufficiency of the locus in independent subjects, may be a first step towards highlighting putative positional effects, though definitive conclusions will still require functional validation. Expression studies in peripheral cells of individual subjects are a plausible, yet suboptimal, method for confirming positional effects. There is clearly a need for sensitive and specific tools to predictive such positional effects caused by long-range regulatory perturbations, and to further annotate the morbid genome with more complete knowledge of these functional interactions. The fraction of BCAs in this study that may be associated with this pathogenic mechanism is thus just an initial glimpse into their likely significance as a component of the unexplained genetic contribution to human birth defects.In terms of evaluating diagnostic strategies, this study this study further highlights the limitations of current diagnostic tools such as karyotyping or CMA in detecting BCAsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5WZXJndWx0PC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 10,13-16. 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 co-author, Dorothy Warburton ADDIN EN.CITE <EndNote><Cite><Author>Warburton</Author><Year>1991</Year><RecNum>1040</RecNum><DisplayText><style face="superscript">9</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 25. Whole-genome sequencing in our cohort suggest that, even at the resolution of 100 kb, only about 12% of BCAs involved a genomic imbalance. If we considered the 168 subjects for which no CMA was previously performed, this proportion increases to 18.1%, suggesting 81.9% of BCAs in this study would be inaccessible to CMA analyses at 100 kb resolution, and 84.1% would be blind to BCAs at 500 kb resolution. Nonetheless, the benefit of an initial CMA screen seems evident: the yield of pathogenic variation was significantly lower among probands that had been pre-screened by CMA (19-37%) compared to those that had not (38-51%; Fig. 2e). These data strongly argue for the implementation of technologies capable of detecting both BCAs and CNVs. At present, this likely involves a conventional cytogenetic test followed by a reflex WGS analysis when an abnormality is detected, which we have previously demonstrated can be accomplished in a relatively rapid timeframe PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWxrb3dza2k8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFy
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ADDIN EN.CITE.DATA 67. Despite its great promise, it is important to recognize the limitations of massively parallel sequencing in routine cytogenetic practice. This study used large-insert jumping libraries to maximize physical coverage and minimize cost per base of genome covered. Yet these analyses failed to reveal breakpoints in 9% of BCAs tested, and our simulations indicate that at large sample sizes, we would anticipate ~7-8% of breakpoints to be undetectable by short-read sequencing. This result illuminates the importance of visualization of structural changes in the genome that are recalcitrant to massively parallel sequencing. As sequencing technologies and analytical capabilities improve, this component of the variant spectrum will become more tractable to genomic approaches, and the future implementation of long-read sequencing may revolutionize the capacity to survey currently inaccessible regions of the human genomePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGFpc3NvbjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+
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ADDIN EN.CITE.DATA 70,64, and more complex oligogenic models. Evaluation of extremely large cohorts will be required to further resolve such mechanisms, and characterization of control populations would further 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.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 that have contributed to the collection of samples. This study was supported by grants from the National Institutes of Health GM061354 (to M.E.T., J.F.G., C.C.M., and E.L.), MH095867 and HD081256 to M.E.T., the March of Dimes 6-FY15-255 and the Desmond and Ann Heathwood MGH Research Scholars award to M.E.T, as well as fellowships from the EMBO (EMBO ALTF-183-2015), the Bettencourt-Schueller Foundation and the Philippe Foundation to C.R. AUTHOR 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., J.T.G., W.P.K., V.P., M.R.S. and M.J.vR. performed computational analyses, C.H., C.M.S., C.A., B.B.C., W.L., and P.M. performed molecular genomic studies, T.K., E.M., J.C.H, MA.A, E.A., F.S.A, K.AY., J.F.A., T.B., E.M.B., E.H.B, C.W.B., H.T.B., B.C., H.C., T.C., M.D., A.D., M.D., B.B.dV., D.L.E., H.L.F., H.F., D.R.F., P.G., T.G., B.H.G., K.W.G., D.J.H., M.H., R.H., J.D.H., M.W.H., A.M.I., S.J., J.P.J., M.C.J., S.G.K, D.A.K., P.M.K., Y.L., W.L., W.L., K.L., A.V.L., B.L., E.C.L., C.L., E.J.L., D.L., M.J.M., P.M., C.L.M., B.M., L.R.M., T.M., G.M., A.N., Z.O., S.P., S.P.P., S.P., P.J.P., S.R., D.R., I.R., F.R., P.R., S.L.P.T., B.W.vB., J.vdK., T.vE., C.M.vR, S.V., N.VT., D.P.W., S.W., R.T.Z., H.G.B., N.d.L., W.P.K., E.C.T., C.C.M, collected samples and phenotype information. C.R. and M.E.T. wrote the manuscript, which was approved by all PETING FINANCIAL INTERESTSThe authors have none to declare.SUPPLEMENTARY INFORMATIONSupplementary material is available online and contains Supplementary Methods, ten Supplementary Tables and 60 Supplementary Figures.ONLINE METHODSSubjects 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, Nijmegen Medical Center, Nijmegen, NL. Enrollment was based on the presence of a developmental anomaly and concomitant detection by karyotyping of a BCA (de novo or that segregated with the abnormal phenotype), and exclusion of clinically significant genomic copy number imbalances using chromosomal microarray analyses (SNP array or array-CGH) when possible (168/273 tested subjects; Supplementary Fig. S1). 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) subjects. An informed consent was obtained from all subjects or their legal representative for the participation in the study. All studies were approved by respective Institutional Review Boards.Whole-genome sequencing using large-insert jumping librariesSamples were prepared using multiple sequencing methods over several years (Supplementary Table 1). Most samples were sequenced using whole-genome large-insert jumping library preparation protocols for subsequent Illumina sequencing: 150 using our 2x25-bp EcoP15l protocolPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWxrb3dza2k8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy
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ADDIN EN.CITE.DATA 10,71, 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 Methods) and 30 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=2) or targeted sequencing of the breakpoints based on previous positional cloning to narrow the breakpoint regions (n=34), as previously describedPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IaWdnaW5zPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48
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ADDIN EN.CITE.DATA 72,10,12. Of note, 89 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 the Human Phenotype Ontology (HPO; Supplementary Table 2)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JYm4tU2FsZW08L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA 64. 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 PhenomizerPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hsZXI8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 73. 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 S9) ADDIN EN.CITE <EndNote><Cite><Author>Deng</Author><Year>2015</Year><RecNum>1116</RecNum><DisplayText><style face="superscript">65</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)
1932-6203 (Linking)</isbn><accession-num>25664462</accession-num><urls><related-urls><url> discovery pipeline and breakpoint inferenceAll computational analyses have been previously described (ref LOGIC, Paired-Dups). 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">74</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 10,75. Anomalous read-pair clusters meeting our established thresholds of structural variation (ref Paired-Dups) were subsequently classified based on their read-pair orientation signature into the following categories: deletions, insertions, inversions, and translocations. 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 are computed relative to the successfully mapped cases (n=248). For the remaining 25 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 blind spots for short-read alignments. When additional DNA was available, precise breakpoint junctions were delineated at base-pair resolution by Sanger sequencing and the final breakpoints coordinates were reported; else the reported coordinates reflect the minimal breakpoint estimates based on the resolution of the jumping libraries (Supplementary Table 3). A total 76% (725/874) of the reported breakpoints could by tested by Sanger sequencing given DNA availability, among which 662 were eventually confirmed yielding an estimated 91.3% (662/725) sensitivity for our mapping method.Molecular signature of BCA breakpointsAlike previously described PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGlhbmc8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 23, we processed all Sanger sequences from validated breakpoints with the BWA Smith-Waterman algorithm (modified parameters z 100 -t 3 -H -T 1) in order to retrieve precise breakpoint coordinates as well as infer the associated microhomology, micro-insertions or blunt end signature. This approach was high-throughput enough to enable the direct comparison of BCA breakpoints with a large set of deletion breakpoints published by another group PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYnl6b3Y8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 76, at the cost of not allowing concomitant microhomology and base insertions at breakpoints.Monte-Carlo randomization testsA Browser Extensible Data (BED) file containing GRCh37/hg19 genomic coordinates of all 874 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 the 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 the cohort 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 in the actual cohort, 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">77</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>. The 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 S10.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 Methods for detailed references). 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 amalgamayed 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 S5-S7). Likely Pathogenic: Novel candidate genes or mechanisms. To evaluate the impact of the remaining BCAs and the genes they likely impacted on, 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, via various mechanisms (Supplementary Table S5-6, S8): (1) Disruption of a likely risk factor: Disruption of one copy of a gene in which at most 2 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 mutations while we reported LoF, or LoF when we reported full gene duplication)(3) Disruption of long-range interactions: BCA breakpoints located in the vicinity of a gene associated with dominant developmental disorders in a subject with consistent phenotype, and predicted to impact on 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 57,18, and genes contained within a domain for which at least one of its insulating boundaries was disrupted by a BCA were collected. Only genes that had been previously robustly associated to dominant developmental disorders (i.e. with dnLoF reported in 3 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 the subjects identified with a BCA of plausible positional effect, the region was visualized using JuiceboxPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdXJhbmQ8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 18,78 (Supplementary Fig. S10-15). Heatmaps represent observed intrachromosomal interactions in GM12878 lymphoblastoid cells in a specific window; previously reported contact domains (regions of increased contact, not necessarily materializing as loops) and loops (sites of increased focal contacts indicating the presence of a loop) were indicated PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SYW88L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 57,18, as well as the RefSeq genes located in the region.Measuring gene expression from lymphoblastsIn subjects for which the BCA was suspected to result in positional effects and for whom LCLs derived from blood were available, gene expression was investigated by quantitative real-time RT-PCR. Of note, LCLs were not tested for mycoplasma contamination. Of note, 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, DGA222; NDP: DGAP100; SATB2: DGAP237; SLC2A1: DGAP170; SRCAP: DGAP134) using custom designed primers (see Supplementary Methods). 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 three technical replicates. Results of technical replicates 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 NDP, SATB2, SLC2A1 and SRCAP, or sixteen (8 males, 8 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 qPCR results were independently replicated twice in the laboratory.TABLES Table 1. Overview of clinical phenotypes for all 273 subjects.Affected/Total subjectsFrequencyin cohortGenderMale159/27358%Female114/27342%Co-SegregationDe novo184/27367%Unknown75/27327%Inherited, segregating14/2235%array-CGH analysesNormal135/27349%VUS33/27320%Not Performed105/27338%Abdomen defects54/27320%Cardiovascular defects41/27315%Eye defects54/27320%Hearing defects52/27319%Genitourinary defects50/27318%Growth defects64/27323%Head/Neck/Cranofacial defects140/27351%Integument defects50/27318%Limb defects57/27321%Musculature defects71/27326%Neurological defects219/27380%Behavior disorders51/27319%Developmental delay159/27358%Epilepsy51/27319%Hypotonia41/27315%ASD/autistic features31/27311%High functioning ASD4/2731%Respiratory defects30/27311%Skeletal defects116/27342% FIGURESFigure 1. Characteristics of cytogenetically detected BCAs when mapped at nucleotide resolution013335000a. Circos plot of all BCA breakpoints identified in the cohort by whole-genome sequencing and their distribution across all chromosomes ADDIN EN.CITE <EndNote><Cite><Author>Krzywinski</Author><Year>2009</Year><RecNum>1126</RecNum><DisplayText><style face="superscript">79</style></DisplayText><record><rec-number>1126</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1470755421">1126</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; b. Scatter plot summarizing the overall genomic imbalance associated with all reconstructed BCAs (n=238) at different size thresholds. Curves represent the fraction of cases with final genomic imbalances greater of the corresponding size provided. The solid lines denote the final genomic imbalances for all BCAs (n=238), and are further delineated by deletions (red) or duplications (blue) emphasizing that cryptic imbalances connected to breakpoints are predominantly copy-losses. The final genomic imbalances among fully mapped BCAs is also split between cases that have been pre-screened by chromosomal microarray (CMA; dashed line; n=150) versus cases without CMA data (dotted line, n=88). CMA may denote distinct clinical aCGH and CMA platforms as performed by individual clinical sites; c. Sequence signatures of BCA breakpoints in the cohort. Histogram representing nucleotide signatures at the junction of 662 Sanger-validated breakpoints: inserted nucleotides (blue), blunt ends (grey), microhomology (orange), or longer stretches of homology (red). Figure 2. De novo BCAs associated with congenital anomalies disrupt functionally relevant loci 05334000a. Genes localized to BCA breakpoints in subjects with congenital anomalies were significantly enriched for constrained genes (1: Petrovski et al. ADDIN EN.CITE <EndNote><Cite><Author>Petrovski</Author><Year>2013</Year><RecNum>873</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>873</rec-number><foreign-keys><key app="EN" db-id="5vfw5rsv9xdtp5eeaevppz2v9dvtvaztrxtt" timestamp="1447092738">873</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Petrovski, S.</author><author>Wang, Q.</author><author>Heinzen, E. L.</author><author>Allen, A. S.</author><author>Goldstein, D. B.</author></authors></contributors><auth-address>Center for Human Genome Variation, Duke University, School of Medicine, Durham, North Carolina, United States of America. slave.petrovski@duke.edu</auth-address><titles><title>Genic intolerance to functional variation and the interpretation of personal genomes</title><secondary-title>PLoS Genet</secondary-title></titles><periodical><full-title>PLoS Genet</full-title></periodical><pages>e1003709</pages><volume>9</volume><number>8</number><keywords><keyword>*Exome</keyword><keyword>Genetic Diseases, Inborn/*genetics/pathology</keyword><keyword>*Genetic Variation</keyword><keyword>*Genome, Human</keyword><keyword>Humans</keyword><keyword>Individualized Medicine</keyword><keyword>Mutation</keyword></keywords><dates><year>2013</year></dates><isbn>1553-7404 (Electronic)
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ADDIN EN.CITE.DATA 29 [P=0.0009]), embryonically-expressed genes (P=0.001), genes previously associated to autosomal dominant disorders (P=0.002), principally developmental disorders (P=0.00002), FMRP-target genes (1: Ascano et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bc2Nhbm88L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 33, and [P=0.036], and 2: Darnell et al.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYXJuZWxsPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA 18. Forward (green) and reverse (red) CTCF binding sites that overlap with MEF2C-associated loop and domain boundaries are shown; c. A 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 was observed in LCLs from subjects harboring BCAs that disrupt the MEF2C-associated TADs when compared to age-matched controls (DGAP131: P=0.009, DGAP191: P=0.009, DGAP218: P=0.016, DGAP222: P=0.009), suggesting regulatory changes via a positional effect that disrupts the MEF2C TAD based on real-time RT-PCR compared to mean expression value from 16 age-matched controls using three technical replicates and normalized against the average of the three endogenous controls (ACTB, GAPDH and POLR2A). Differential gene expression was tested using a Wilcoxon Mann-Whitney test (* P<0.05, ** P<0.01). Figure 4. Broad genotype-to-phenotype correlations in subjects harboring pathogenic BCAscenter317500Heatmap summarizing the correlation between disrupted genes at breakpoints of pathogenic BCAs and phenotypes reported in probands. For each gene, the phenotypes reported in the corresponding subject were digitalized using HPO terms and grouped together under broad HPO categories. One tile represents the count of HPO terms belonging to each broad category reported in the subject(s). The generated matrix of HPO-terms count per category for each gene was normalized per gene, and genes were clustered together when sharing similarly affected organs. Five groups are delineated based on clustering: 1- genes associated with severe nervous system and cranofacial abnormalities (dark blue); 2- genes connected to severe neurological phenotypes (red); 3- genes associated with cranofacial abnormalities and moderate neurological symptoms; 4- genes associated with skeletal and limb abnormalities, and with milder neurological involvement; 5- genes without neurological involvement (urogenital, respiratory, etc).REFERENCES ADDIN EN.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.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).8.Warburton, D. Current techniques in chromosome analysis. Pediatr. Clin. North Am. 27, 753-769 (1980).9.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).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.Talkowski, M.E. et al. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell 149, 525-537 (2012).13.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).14.Utami, K.H. et al. Detection of chromosomal breakpoints in patients with developmental delay and speech disorders. PLoS One 9, e90852 (2014).15.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).16.Tabet, A.C. et al. Complex nature of apparently balanced chromosomal rearrangements in patients with autism spectrum disorder. Mol. Autism 6, 19 (2015).17.Jin, F. et al. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 503, 290-294 (2013).18.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).19.Kohler, S. et al. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. Nucleic Acids Res. 42, D966-974 (2014).20.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).21.Meyerson, M. & Pellman, D. Cancer genomes evolve by pulverizing single chromosomes. Cell 144, 9-10 (2011).22.Stephens, P.J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144, 27-40 (2011).23.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).24.Baca, S.C. et al. Punctuated evolution of prostate cancer genomes. Cell 153, 666-677 (2013).25.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).26.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).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.Hawrylycz, M.J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391-399 (2012).39.Fromer, M. et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 506, 179-184 (2014).40.Purcell, S.M. et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 506, 185-190 (2014).41.Landrum, M.J. et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 44, D862-868 (2016).42.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).43.Lu, W. et al. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects. PLoS Genet 3, e80 (2007).44.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).45.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).46.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).47.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).48.Simpson, M.A. et al. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat. Genet. 43, 303-305 (2011).49.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).50.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).51.Cardoso, C. et al. Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion. Neurology 72, 784-792 (2009).52.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).53.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).54.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).55.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).56.Zweier, M. & Rauch, A. TheMEF2C-Related and 5q14.3q15 Microdeletion Syndrome. Mol. Syndromol. 2, 164-170 (2011).57.Dixon, J.R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380 (2012).58.Lupianez, D.G. et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161, 1012-1025 (2015).59.Lupianez, D.G., Spielmann, M. & Mundlos, S. Breaking TADs: How Alterations of Chromatin Domains Result in Disease. Trends Genet. 32, 225-237 (2016).60.Mencarelli, M.A. et al. 14q12 Microdeletion syndrome and congenital variant of Rett syndrome. Eur. J. Med. Genet. 52, 148-152 (2009).61.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).62.Perche, O. et al. Dysregulation of FOXG1 pathway in a 14q12 microdeletion case. Am. J. Med. Genet. A 161A, 3072-3077 (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.Ibn-Salem, J. et al. Deletions of chromosomal regulatory boundaries are associated with congenital disease. Genome Biol. 15, 423 (2014).65.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).66.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).67.Brand, H. et al. Cryptic and complex chromosomal aberrations in early-onset neuropsychiatric disorders. Am. J. Hum. Genet. 95, 454-461 (2014).68.Huddleston, J. et al. Reconstructing complex regions of genomes using long-read sequencing technology. Genome Res. 24, 688-696 (2014).69.Chaisson, M.J. et al. Resolving the complexity of the human genome using single-molecule sequencing. Nature 517, 608-611 (2015).70.Lettice, L.A. et al. Enhancer-adoption as a mechanism of human developmental disease. Hum. Mutat. 32, 1492-1499 (2011).71.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).72.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).73.Kohler, S. et al. Clinical diagnostics in human genetics with semantic similarity searches in ontologies. Am. J. Hum. Genet. 85, 457-464 (2009).74.Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009).75.Tarasov, A., Vilella, A.J., Cuppen, E., Nijman, I.J. & Prins, P. Sambamba: fast processing of NGS alignment formats. Bioinformatics 31, 2032-2034 (2015).76.Abyzov, A. et al. Analysis of deletion breakpoints from 1,092 humans reveals details of mutation mechanisms. Nat Commun 6, 7256 (2015).77.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).78.Durand, N.C. et al. Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom. Cell Syst 3, 99-101 (2016).79.Krzywinski, M. et al. Circos: an information aesthetic for comparative genomics. Genome Res. 19, 1639-1645 (2009). ................
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