Integrating healthcare and research genetic data empowers the discovery of 28 novel 1 developmental disorders 2 3

developmental disorders 2 3 Joanna Kaplanis*, Kaitlin E. Samocha*, Laurens Wiel*, Zhancheng Zhang*, Kevin J. Arvai, 4 Ruth Y. Eberhardt, Giuseppe Gallone, Stefan H. Lelieveld, Hilary C. Martin, Jeremy F. 5 McRae, Patrick J. Short, Rebecca I. Torene, Elke de Boer, Petr Danecek, Eugene J. 6 Gardner, Ni Huang, Jenny Lord, Iñigo Martincorena, Rolph Pfundt, Margot R. F. 7 Reijnders, Alison Yeung, Helger G. Yntema, DDD Study, Lisenka E. L. M. Vissers, Jane 8 Juusola, Caroline F. Wright, Han G. Brunner, Helen V. Firth, David R. FitzPatrick, 9 Jeffrey C. Barrett, Matthew E. Hurles†, Christian Gilissen, Kyle Retterer 10

[1]  Matthew W. Mosconi,et al.  Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism , 2019, Cell.

[2]  Seth I. Berger,et al.  TFE3‐associated neurodevelopmental disorder: A distinct recognizable syndrome , 2019, American journal of medical genetics. Part A.

[3]  Maximilian E. R. Weiss,et al.  De Novo Variants in TAOK1 Cause Neurodevelopmental Disorders. , 2019, American journal of human genetics.

[4]  R. Hochstenbach,et al.  Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features , 2019, American journal of medical genetics. Part A.

[5]  Nancy T. Malintan,et al.  Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment , 2019, American journal of human genetics.

[6]  E. van Binsbergen,et al.  De Novo Missense Substitutions in the Gene Encoding CDK8, a Regulator of the Mediator Complex, Cause a Syndromic Developmental Disorder , 2019, American journal of human genetics.

[7]  Carol J. Saunders,et al.  Heterozygous variants in KMT2E cause a spectrum of neurodevelopmental disorders and epilepsy , 2019, bioRxiv.

[8]  Michael B. Stadler,et al.  Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3. , 2019, Cell stem cell.

[9]  Jay F Rowland,et al.  Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study , 2019, The Lancet.

[10]  H. Mefford,et al.  ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder. , 2019, American journal of human genetics.

[11]  Ryan L. Collins,et al.  Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes , 2019, bioRxiv.

[12]  David G. Knowles,et al.  Predicting Splicing from Primary Sequence with Deep Learning , 2019, Cell.

[13]  Ellen F. Macnamara,et al.  De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A, PPP2CA, Cause Syndromic Intellectual Disability Resembling Other PP2A-Related Neurodevelopmental Disorders. , 2019, American journal of human genetics.

[14]  Joan,et al.  Prevalence and architecture of de novo mutations in developmental disorders , 2017, Nature.

[15]  James D Stephenson,et al.  Quantifying the contribution of recessive coding variation to developmental disorders , 2017, Science.

[16]  Trygve E Bakken,et al.  Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity , 2018, Nature Genetics.

[17]  Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes. , 2018, Genome research.

[18]  F. McCormick,et al.  SHOC2–MRAS–PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis , 2018, Proceedings of the National Academy of Sciences.

[19]  Ivan K. Chinn,et al.  Identifying Genes Whose Mutant Transcripts Cause Dominant Disease Traits by Potential Gain-of-Function Alleles. , 2018, American journal of human genetics.

[20]  Birgit Sikkema-Raddatz,et al.  Improving the diagnostic yield of exome- sequencing by predicting gene–phenotype associations using large-scale gene expression analysis , 2018, Nature Communications.

[21]  L. A. Lowery,et al.  The Role of the Microtubule Cytoskeleton in Neurodevelopmental Disorders , 2018, Front. Cell. Neurosci..

[22]  M. Stratton,et al.  Universal Patterns of Selection in Cancer and Somatic Tissues , 2018, Cell.

[23]  K. Heimdal,et al.  Heterozygous mutations affecting the protein kinase domain of CDK13 cause a syndromic form of developmental delay and intellectual disability , 2017, Journal of Medical Genetics.

[24]  M. Daly,et al.  Regional missense constraint improves variant deleteriousness prediction , 2017, bioRxiv.

[25]  Deciphering Developmental Disorders Study,et al.  Prevalence and architecture of de novo mutations in developmental disorders , 2017, Nature.

[26]  David P. Nusinow,et al.  Estimating the Selective Effects of Heterozygous Protein Truncating Variants from Human Exome Data , 2017, Nature Genetics.

[27]  Stephan J Sanders,et al.  Refining the role of de novo protein truncating variants in neurodevelopmental disorders using population reference samples , 2016, Nature Genetics.

[28]  W. Chung,et al.  Deep Genetic Connection Between Cancer and Developmental Disorders , 2016, Human mutation.

[29]  E. Giannoulatou,et al.  Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes , 2016, Proceedings of the National Academy of Sciences.

[30]  James Y. Zou Analysis of protein-coding genetic variation in 60,706 humans , 2015, Nature.

[31]  J. Clayton-Smith,et al.  A recurrent synonymous KAT6B mutation causes Say‐Barber‐Biesecker/Young‐Simpson syndrome by inducing aberrant splicing , 2015, American journal of medical genetics. Part A.

[32]  Tomas W. Fitzgerald,et al.  Large-scale discovery of novel genetic causes of developmental disorders , 2014, Nature.

[33]  M. Okano,et al.  Cohort Study , 2020, Definitions.

[34]  Kali T. Witherspoon,et al.  Refining analyses of copy number variation identifies specific genes associated with developmental delay , 2014, Nature Genetics.

[35]  J. Shendure,et al.  A general framework for estimating the relative pathogenicity of human genetic variants , 2014, Nature Genetics.

[36]  Joshua M. Stuart,et al.  The Cancer Genome Atlas Pan-Cancer analysis project , 2013, Nature Genetics.

[37]  Kathryn Roeder,et al.  Integrated Model of De Novo and Inherited Genetic Variants Yields Greater Power to Identify Risk Genes , 2013, PLoS genetics.

[38]  Xiaomei Wu,et al.  Improving the Measurement of Semantic Similarity between Gene Ontology Terms and Gene Products: Insights from an Edge- and IC-Based Hybrid Method , 2013, PloS one.

[39]  Wei Wu,et al.  From neural development to cognition: unexpected roles for chromatin , 2013, Nature Reviews Genetics.

[40]  A. Wilkie,et al.  Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. , 2012, American journal of human genetics.

[41]  Gregory M. Cooper,et al.  A Copy Number Variation Morbidity Map of Developmental Delay , 2011, Nature Genetics.

[42]  Helga Thorvaldsdóttir,et al.  Integrative Genomics Viewer , 2011, Nature Biotechnology.

[43]  S. Dib-Hajj,et al.  Inherited Neuronal Ion Channelopathies: New Windows on Complex Neurological Diseases , 2008, The Journal of Neuroscience.

[44]  Jeffrey H. Miller,et al.  Mutagenic deamination of cytosine residues in DNA , 1980, Nature.