The mutational constraint spectrum quantified from variation in 141,456 humans

Irina M. Armean | Judy H. Cho | Y. J. Kim | T. Spector | M. McCarthy | E. Banks | K. Cibulskis | S. Gabriel | M. Daly | D. MacArthur | T. Lehtimäki | J. Suvisaari | M. Owen | M. O’Donovan | P. Sullivan | S. Mccarroll | G. Getz | J. Rioux | V. Salomaa | E. Vartiainen | R. Xavier | M. Chung | L. Groop | M. Laakso | M. Boehnke | B. Neale | D. Chasman | N. Samani | N. Rahman | Y. Teo | C. Albert | E. Benjamin | P. Ellinor | K. Karczewski | R. Duggirala | J. Kaprio | J. Erdmann | H. Schunkert | C. Haiman | H. Soininen | D. Roden | Jeff Gentry | A. Palotie | S. Ripatti | A. Metspalu | T. Esko | P. Sklar | C. Hultman | M. Lek | E. Minikel | L. Bonnycastle | S. Kathiresan | J. Florez | O. Melander | D. Ardissino | J. Meigs | J. Dupuis | S. Ferriera | Z. Zappala | M. Hiltunen | A. Franke | K. Samocha | R. McPherson | A. O’Donnell-Luria | J. Ware | B. Cummings | Daniel P Birnbaum | J. Kosmicki | E. Pierce-Hoffman | L. Gauthier | N. Gupta | L. Orozco | Valentín Ruano-Rubio | G. Tiao | B. Weisburd | S. Donnelly | R. Elosua | S. Glatt | D. Saleheen | J. Scharf | H. Watkins | James G. Wilson | L. Francioli | S. Koskinen | J. Kooner | R. Collins | H. Brand | M. Talkowski | E. Bottinger | J. Barnard | A. Correa | D. Bowden | J. Chambers | R. Loos | H. Sokol | C. Palmer | A. Ganna | R. Weersma | S. Kugathasan | M. Holi | J. Marrugat | David Roazen | K. Connolly | R. Walters | M. Bown | D. Ongur | S. Lubitz | A. Pulver | Jessica Alföldi | Qingbo S. Wang | K. Laricchia | M. Solomonson | N. Watts | Daniel Rhodes | M. Singer-Berk | E. Seaby | K. Tashman | Y. Farjoun | T. Poterba | Arcturus Wang | C. Seed | N. Whiffin | J. Chong | C. Vittal | Louis Bergelson | Miguel Covarrubias | Thibault Jeandet | D. Kaplan | Christopher Llanwarne | Ruchi Munshi | Sam Novod | Nikelle Petrillo | A. Saltzman | M. Schleicher | J. Soto | Kathleen M. Tibbetts | C. Tolonen | Gordon Wade | M. Färkkilä | Bong-Jo Kim | S. Kwak | G. Atzmon | M. Wessman | M. Kallela | Tariq Ahmad | D. Darbar | D. Dabelea | T. Tusié-Luna | David Goldstein | M. Shoemaker | D. Turner | L. Beaugerie | Juliana C. N. Chan | A. Remes | E. England | S. Ferriera | Carlos A. Tariq Christine M. Diego Gil John Laurent Emeli Aguilar Salinas Ahmad Albert Ardissino Atz | C. A. Aguilar Salinas | Bruce M. Cohen | Benjamin Glaser | C. Gonzalez | Craig Hanis | Matthew S. Harms | G. Kirov | H. Krumholz | Ronald C W Ma | K. Mattila | D. McGovern | Peter M. Nilsson | K. Park | Carlos Pato | E. S. Tai | Tuomi Tiinamaija | M. Tsuang | Jessica X. Chong | Daniel Birnbaum

[1]  Ryan L. Collins,et al.  The effect of LRRK2 loss-of-function variants in humans , 2020, Nature Medicine.

[2]  Tariq Ahmad,et al.  A structural variation reference for medical and population genetics , 2020, Nature.

[3]  Jonathan M. Mudge,et al.  Transcript expression-aware annotation improves rare variant interpretation , 2020, Nature.

[4]  M. Hall.  National Heart, Lung, and Blood Institute , 2020, The Grants Register 2021.

[5]  Ryan L. Collins,et al.  Evaluating drug targets through human loss-of-function genetic variation , 2019, Nature.

[6]  Alex Diaz-Papkovich,et al.  UMAP reveals cryptic population structure and phenotype heterogeneity in large genomic cohorts , 2019, PLoS genetics.

[7]  Jakob Grove,et al.  Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have a similar burden of rare protein-truncating variants , 2019, Nature Neuroscience.

[8]  CRISPR-Cas9-based mutagenesis frequently provokes on-target mRNA misregulation , 2019, Nature Communications.

[9]  Michael J Bamshad,et al.  Mendelian Gene Discovery: Fast and Furious with No End in Sight. , 2019, American journal of human genetics.

[10]  G. Sella,et al.  Measuring intolerance to mutation in human genetics , 2018, Nature Genetics.

[11]  D. Stainier,et al.  Genetic compensation triggered by mutant mRNA degradation , 2019, Nature.

[12]  Alicia R. Martin,et al.  Clinical use of current polygenic risk scores may exacerbate health disparities , 2019, Nature Genetics.

[13]  D. Mathews,et al.  CRISPR-Cas9-based mutagenesis frequently provokes on-target mRNA misregulation , 2019, Nature Communications.

[14]  Grace Tiao,et al.  An open resource of structural variation for medical and population genetics , 2019 .

[15]  Beryl B. Cummings,et al.  Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes , 2019, bioRxiv.

[16]  Beryl B. Cummings,et al.  Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinson’s disease , 2019, bioRxiv.

[17]  Jonathan M. Mudge,et al.  Transcript expression-aware annotation improves rare variant discovery and interpretation , 2019, bioRxiv.

[18]  Tariq Ahmad,et al.  Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals , 2019, bioRxiv.

[19]  Beryl B. Cummings,et al.  Evaluating potential drug targets through human loss-of-function genetic variation , 2019, bioRxiv.

[20]  P. Hainaut,et al.  Variable population prevalence estimates of germline TP53 variants: A gnomAD‐based analysis , 2018, Human mutation.

[21]  J. Pritchard,et al.  Evidence for Weak Selective Constraint on Human Gene Expression , 2018, Genetics.

[22]  Alicia R. Martin,et al.  Hidden ‘risk’ in polygenic scores: clinical use today could exacerbate health disparities , 2018, bioRxiv.

[23]  Alex Diaz-Papkovich,et al.  Revealing multi-scale population structure in large cohorts , 2018, bioRxiv.

[24]  Leland McInnes,et al.  UMAP: Uniform Manifold Approximation and Projection , 2018, J. Open Source Softw..

[25]  G. Sella,et al.  Measuring intolerance to mutation in human genetics , 2018, Nature Genetics.

[26]  Joseph D. Janizek,et al.  Accurate classification of BRCA1 variants with saturation genome editing , 2018, Nature.

[27]  Benjamin Neale,et al.  A synthetic-diploid benchmark for accurate variant calling evaluation , 2018, Nature Methods.

[28]  Alicia R. Martin,et al.  Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum. , 2018, American journal of human genetics.

[29]  Jörg Hakenberg,et al.  Predicting the clinical impact of human mutation with deep neural networks , 2018, Nature Genetics.

[30]  Mary E. Haas,et al.  Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease , 2018, Nature Communications.

[31]  Caroline F. Wright,et al.  De novo mutations in regulatory elements in neurodevelopmental disorders , 2018, Nature.

[32]  M. Daly,et al.  ASD and ADHD have a similar burden of rare protein-truncating variants , 2018, bioRxiv.

[33]  Bryce K. Allen,et al.  Comprehensive Analysis of Tissue-wide Gene Expression and Phenotype Data Reveals Tissues Affected in Rare Genetic Disorders. , 2018, Cell systems.

[34]  Nicola J. Rinaldi,et al.  Genetic effects on gene expression across human tissues , 2017, Nature.

[35]  Hannes P. Eggertsson,et al.  Parental influence on human germline de novo mutations in 1,548 trios from Iceland , 2017, Nature.

[36]  M. Rivas,et al.  Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study , 2018, Nature Communications.

[37]  K. Eilbeck,et al.  Settling the score: variant prioritization and Mendelian disease , 2017, Nature Reviews Genetics.

[38]  M. Weedon,et al.  Analysis of large‐scale sequencing cohorts does not support the role of variants in UCP2 as a cause of hyperinsulinaemic hypoglycaemia , 2017, Human mutation.

[39]  D. Durocher,et al.  Evaluation and Design of Genome-Wide CRISPR/SpCas9 Knockout Screens , 2017, G3: Genes, Genomes, Genetics.

[40]  Elvira Bramon,et al.  The contribution of rare variants to risk of 1 schizophrenia in individuals with and without 2 intellectual disability , 2017 .

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

[42]  Giulio Genovese,et al.  Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia , 2016, Nature Neuroscience.

[43]  Patrick F. Sullivan,et al.  Ultra-rare disruptive and damaging mutations influence educational attainment in the general population , 2016, Nature Neuroscience.

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

[45]  S. Gravel.  When Is Selection Effective? , 2014, Genetics.

[46]  Yakir A Reshef,et al.  Partitioning heritability by functional annotation using genome-wide association summary statistics , 2015, Nature Genetics.

[47]  Ayal B. Gussow,et al.  The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity , 2015, PLoS genetics.

[48]  Karynne E. Patterson,et al.  The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. , 2015, American journal of human genetics.

[49]  J. E. Richardson,et al.  MouseMine: a new data warehouse for MGI , 2015, Mammalian Genome.

[50]  A. Clark,et al.  Estimating the mutation load in human genomes , 2015, Nature Reviews Genetics.

[51]  Judith A. Blake,et al.  The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease , 2014, Nucleic Acids Res..

[52]  Korbinian Schneeberger,et al.  Using next-generation sequencing to isolate mutant genes from forward genetic screens , 2014, Nature Reviews Genetics.

[53]  Stephan J Sanders,et al.  A framework for the interpretation of de novo mutation in human disease , 2014, Nature Genetics.

[54]  J. Zook,et al.  Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls , 2013, Nature Biotechnology.

[55]  E. Banks,et al.  De novo mutations in schizophrenia implicate synaptic networks , 2014, Nature.

[56]  Mauricio O. Carneiro,et al.  From FastQ Data to High‐Confidence Variant Calls: The Genome Analysis Toolkit Best Practices Pipeline , 2013, Current protocols in bioinformatics.

[57]  D. Goldstein,et al.  Correction: Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes , 2013, PLoS Genetics.

[58]  D. Goldstein,et al.  Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes , 2013, PLoS genetics.

[59]  Evan T. Geller,et al.  Patterns and rates of exonic de novo mutations in autism spectrum disorders , 2012, Nature.

[60]  Joseph K. Pickrell,et al.  A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes , 2012, Science.

[61]  Avner Schlessinger,et al.  ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI , 2012 .

[62]  E. Perez-stable,et al.  Division of General Internal Medicine , 2009 .

[63]  Jonathan C. Cohen,et al.  Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. , 2006, The New England journal of medicine.

[64]  A. Sands,et al.  Knockouts model the 100 best-selling drugs—will they model the next 100? , 2003, Nature Reviews Drug Discovery.