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Ryan L. Collins

ORCID: 0000-0003-1268-9995
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A5022093098
Research Areas
  • Genomics and Rare Diseases
  • Genomic variations and chromosomal abnormalities
  • Genomics and Phylogenetic Studies
  • CRISPR and Genetic Engineering
  • Autism Spectrum Disorder Research
  • Genetics and Neurodevelopmental Disorders
  • Cancer Genomics and Diagnostics
  • Congenital heart defects research
  • Chromosomal and Genetic Variations
  • RNA and protein synthesis mechanisms
  • Genetic Associations and Epidemiology
  • Prenatal Screening and Diagnostics
  • Genomics and Chromatin Dynamics
  • RNA modifications and cancer
  • Adipose Tissue and Metabolism
  • Genetic Neurodegenerative Diseases
  • Genetics, Bioinformatics, and Biomedical Research
  • Congenital Ear and Nasal Anomalies
  • RNA Research and Splicing
  • RNA regulation and disease
  • Neurological diseases and metabolism
  • Craniofacial Disorders and Treatments
  • Parkinson's Disease Mechanisms and Treatments
  • Single-cell and spatial transcriptomics
  • Connective tissue disorders research

Massachusetts General Hospital
 2015-2025

Harvard University
 2016-2025

Broad Institute
 2016-2025

Dana-Farber Cancer Institute
 2023-2025

Massachusetts Institute of Technology
 2019-2023

QorTek (United States)
 2023

Williams (United States)
 2023

SRM Institute of Science and Technology
 2023

Center for Genomic Science
 2018-2019

Harvard University Press
 2019

 The mutational constraint spectrum quantified from variation in 141,456 humans
OPENALEX - Publications 
Konrad J. Karczewski Laurent C. Francioli Grace Tiao Beryl B. Cummings Jessica Alföldi and 95 more Qingbo Wang Ryan L. Collins Kristen M. Laricchia Andrea Ganna Daniel P. Birnbaum Laura D. Gauthier Harrison Brand Matthew Solomonson Nicholas A. Watts Daniel R. Rhodes Moriel Singer‐Berk Eleina England Eleanor G. Seaby Jack A. Kosmicki Raymond K. Walters Katherine Tashman Yossi Farjoun Eric Banks Timothy Poterba Arcturus Wang Cotton Seed Nicola Whiffin Jessica X. Chong Kaitlin E. Samocha Emma Pierce‐Hoffman Zachary Zappala Anne O’Donnell‐Luria Eric Vallabh Minikel Ben Weisburd Monkol Lek James S. Ware Christopher Vittal Irina M. Armean Louis Bergelson Kristian Cibulskis Kristen M. Connolly Miguel Covarrubias Stacey Donnelly Steven Ferriera Stacey Gabriel Jeff Gentry Namrata Gupta Thibault Jeandet Diane Kaplan Christopher Llanwarne Ruchi Munshi Sam Novod Nikelle Petrillo David Roazen Valentín Ruano-Rubio Andrea Saltzman Molly Schleicher José Soto Kathleen Tibbetts Charlotte Tolonen Gordon Wade Michael E. Talkowski Carlos A. Aguilar‐Salinas Tariq Ahmad Christine M. Albert Diego Ardissino Gil Atzmon John Barnard Laurent Beaugerie Emelia J. Benjamin Michael Boehnke Lori L. Bonnycastle Erwin P. Böttinger Donald W. Bowden Matthew J. Bown John C. Chambers Juliana C.N. Chan Daniel I. Chasman Judy H. Cho Mina K. Chung Bruce M. Cohen Adolfo Correa Dana Dabelea Mark J. Daly Dawood Darbar Ravindranath Duggirala Josée Dupuis Patrick T. Ellinor Roberto Elosúa Jeanette Erdmann Tõnu Esko Martti Färkkilâ José C. Florez André Franke Gad Getz Benjamin Gläser Stephen J. Glatt David Goldstein Clicerio González Leif Groop

Abstract Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences gene disruption: crucial for function an organism will be depleted such in natural populations, whereas non-essential tolerate their accumulation. However, predicted loss-of-function enriched annotation errors, and tend to found at extremely low frequencies, so analysis requires careful variant very large sample sizes 1 . Here we describe aggregation 125,748...

10.1038/s41586-020-2308-7 article EN cc-by Nature 2020-05-27
 Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
OPENALEX - Publications 
F. Kyle Satterstrom Jack A. Kosmicki Jiebiao Wang Michael S. Breen Silvia De Rubeis and 95 more Joon‐Yong An Minshi Peng Ryan L. Collins Jakob Grove Lambertus Klei Christine Stevens Jennifer Reichert Maureen Mulhern Mykyta Artomov Sherif Gerges Brooke Sheppard Xinyi Xu Aparna Bhaduri Utku Norman Harrison Brand Grace Schwartz Rachel Nguyen Elizabeth E. Guerrero Caroline Dias Catalina Betancur Edwin H. Cook Louise Gallagher Michael Gill James S. Sutcliffe Audrey Thurm Michael E. Zwick Anders D. Børglum Matthew W. State A. Ercüment Çiçek Michael E. Talkowski David J. Cutler Bernie Devlin Stephan Sanders Kathryn Roeder Mark J. Daly Joseph D. Buxbaum Branko Aleksić Richard Anney Mafalda Barbosa Somer Bishop Alfredo Brusco Jonas Bybjerg‐Grauholm Ángel Carracedo Marcus C.Y. Chan Andreas G. Chiocchetti Brian Hon‐Yin Chung Hilary Coon Michael L. Cuccaro Aurora Currò Bernardo Dalla Bernardina Ryan N. Doan Enrico Domenici Shan Dong Chiara Fallerini Montserrat Fernández Prieto Giovanni Battista Ferrero Christine M. Freitag Menachem Fromer J. Jay Gargus Daniel H. Geschwind Elisa Giorgio Javier González‐Peñas Stephen J. Guter Danielle Halpern Emily Hansen‐Kiss Xin He Gail E. Herman Irva Hertz‐Picciotto David M. Hougaard Christina M. Hultman Iuliana Ionita‐Laza Suma Jacob Jesslyn Jamison Astanand Jugessur Miia Kaartinen Gun Peggy Knudsen Alexander Kolevzon Itaru Kushima So Lun Lee Terho Lehtimäki Elaine T. Lim Carla Lintas W. Ian Lipkin Diego Lopergolo Fátima Lopes Yunin Ludeña Patrı́cia Maciel Per Magnus Behrang Mahjani Nell Maltman Dara S. Manoach Gal Meiri Idan Menashe Judith Miller Nancy J. Minshew

10.1016/j.cell.2019.12.036 article EN publisher-specific-oa Cell 2020-01-23
 The mutational constraint spectrum quantified from variation in 141,456 humans
OPENALEX - Publications 
Konrad J. Karczewski Laurent C. Francioli Grace Tiao Beryl B. Cummings Jessica Alföldi and 60 more Qingbo Wang Ryan L. Collins Kristen M. Laricchia Andrea Ganna Daniel P. Birnbaum Laura D. Gauthier Harrison Brand Matthew Solomonson Nicholas A. Watts Daniel R. Rhodes Moriel Singer‐Berk Eleina England Eleanor G. Seaby Jack A. Kosmicki Raymond K. Walters Katherine Tashman Yossi Farjoun Eric Banks Timothy Poterba Arcturus Wang Cotton Seed Nicola Whiffin Jessica X. Chong Kaitlin E. Samocha Emma Pierce‐Hoffman Zachary Zappala Anne O’Donnell‐Luria Eric Vallabh Minikel Ben Weisburd Monkol Lek James S. Ware Christopher Vittal Irina M. Armean Louis Bergelson Kristian Cibulskis Kristen M. Connolly Miguel Covarrubias Stacey Donnelly Steven Ferriera Stacey Gabriel Jeff Gentry Namrata Gupta Thibault Jeandet Diane Kaplan Christopher Llanwarne Ruchi Munshi Sam Novod Nikelle Petrillo David Roazen Valentín Ruano-Rubio Andrea Saltzman Molly Schleicher José Soto Kathleen Tibbetts Charlotte Tolonen Gordon Wade Michael E. Talkowski Benjamin M. Neale Mark J. Daly Daniel G. MacArthur

Summary Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences gene disruption: critical for an organism’s function will be depleted such in natural populations, while non-essential tolerate their accumulation. However, predicted loss-of-function (pLoF) enriched annotation errors, and tend to found at extremely low frequencies, so analysis requires careful variant very large sample sizes 1 . Here, we describe aggregation...

10.1101/531210 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2019-01-28
 Multi-platform discovery of haplotype-resolved structural variation in human genomes
OPENALEX - Publications 
Mark Chaisson Ashley D. Sanders Xuefang Zhao Ankit Malhotra David Porubský and 92 more Tobias Rausch Eugene J. Gardner Oscar L. Rodriguez Li Guo Ryan L. Collins Xian Fan Jia Wen Robert E. Handsaker Susan Fairley Zev Kronenberg Xiangmeng Kong Fereydoun Hormozdiari Dillon Lee Aaron M. Wenger Alex Hastie Danny Antaki Thomas Anantharaman Peter A. Audano Harrison Brand Stuart Cantsilieris Han Cao Eliza Cerveira Chong Chen Xintong Chen Chen-Shan Chin Zechen Chong Nelson T. Chuang Christine Lambert Deanna M. Church Laura Clarke Andrew Farrell Joey Flores Timur R. Galeev David U. Gorkin Madhusudan Gujral Victor Guryev Haynes Heaton Jonas Korlach Sushant Kumar Jee Young Kwon Ernest T. Lam Jong Eun Lee Joyce Lee Wan-Ping Lee Sau Peng Lee Shantao Li Patrick Marks Karine A. Viaud‐Martinez Sascha Meiers Katherine M. Munson Fábio C. P. Navarro Bradley J. Nelson Conor Nodzak Amina Noor Sofia Kyriazopoulou-Panagiotopoulou Andy Wing Chun Pang Yunjiang Qiu Gabriel Rosanio Xian Mallory Adrian M. Stütz Diana C.J. Spierings Alistair Ward AnneMarie E. Welch Ming Xiao Wei Xu Chengsheng Zhang Qihui Zhu Xiangqun Zheng-Bradley Ernesto Lowy Sergei Yakneen Steven A. McCarroll Goo Jun Li Ding Chong‐Lek Koh Bing Ren Paul Flicek Ken Chen Mark Gerstein Pui‐Yan Kwok Peter M. Lansdorp Gábor Marth Jonathan Sebat Xinghua Shi Ali Bashir Kai Ye Scott E. Devine Michael E. Talkowski Ryan E. Mills Tobias Marschall Jan O. Korbel Evan E. Eichler Charles Lee

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies human genetic diversity and disease association. Here, we apply a suite long-read, short-read, strand-specific technologies, optical mapping, variant discovery algorithms to comprehensively analyze three trios define the full spectrum variation in haplotype-resolved manner. We identify 818,054 indel (<50 bp) 27,622 SVs (≥50 per genome. also discover 156 inversions genome 58 intersect...

10.1038/s41467-018-08148-z article EN cc-by Nature Communications 2019-04-16
 A structural variation reference for medical and population genetics
OPENALEX - Publications 
Ryan L. Collins Harrison Brand Konrad J. Karczewski Xuefang Zhao Jessica Alföldi and 95 more Laurent C. Francioli Amit V. Khera Chelsea Lowther Laura D. Gauthier Harold Wang Nicholas A. Watts Matthew Solomonson Anne O’Donnell‐Luria Alexander Baumann Ruchi Munshi Mark Walker Christopher W. Whelan Yongqing Huang Ted Brookings Ted Sharpe Matthew R. Stone Elise Valkanas Jack Fu Grace Tiao Kristen M. Laricchia Valentín Ruano-Rubio Christine Stevens Namrata Gupta Caroline Cusick Lauren Margolin Jessica Alföldi Irina M. Armean Eric Banks Louis Bergelson Kristian Cibulskis Ryan L. Collins Kristen M. Connolly Miguel Covarrubias Beryl B. Cummings Mark J. Daly Stacey Donnelly Yossi Farjoun Steven Ferriera Laurent C. Francioli Stacey Gabriel Laura D. Gauthier Jeff Gentry Namrata Gupta Thibault Jeandet Diane Kaplan Konrad J. Karczewski Kristen M. Laricchia Christopher Llanwarne Eric Vallabh Minikel Ruchi Munshi Benjamin M. Neale Sam Novod Anne O’Donnell‐Luria Nikelle Petrillo Timothy Poterba David Roazen Valentín Ruano-Rubio Andrea Saltzman Kaitlin E. Samocha Molly Schleicher Cotton Seed Matthew Solomonson José Soto Grace Tiao Kathleen Tibbetts Charlotte Tolonen Christopher Vittal Gordon Wade Arcturus Wang Qingbo Wang James S. Ware Nicholas A. Watts Ben Weisburd Nicola Whiffin Carlos A. Aguilar‐Salinas Tariq Ahmad Christine M. Albert Diego Ardissino Gil Atzmon J. A. Barnard Laurent Beaugerie Emelia J. Benjamin Michael Boehnke Lori L. Bonnycastle Erwin P. Böttinger Donald W. Bowden Matthew J. Bown John C. Chambers Juliana C.N. Chan Daniel I. Chasman Judy H. Cho Mina K. Chung Bruce M. Cohen Adolfo Correa Dana Dabelea

Structural variants (SVs) rearrange large segments of DNA

10.1038/s41586-020-2287-8 article EN cc-by Nature 2020-05-27
 Genome-wide enhancer maps link risk variants to disease genes
OPENALEX - Publications 
Joseph Nasser Drew T. Bergman Charles P. Fulco Philine Guckelberger Benjamin R. Doughty and 27 more Tejal A. Patwardhan Thouis R. Jones Tung H. Nguyen Jacob C. Ulirsch Fritz Lekschas Kristy S. Mualim Heini M. Natri E. Weeks Glen Munson Michael Kane Helen Y. Kang Ang Cui John Ray Thomas Eisenhaure Ryan L. Collins Kushal K. Dey Hanspeter Pfister Alkes L. Price Charles B. Epstein Anshul Kundaje Ramnik J. Xavier Mark J. Daly Hailiang Huang Hilary K. Finucane Nir Hacohen Eric S. Lander J Engreitz

10.1038/s41586-021-03446-x article EN Nature 2021-04-07
 A genomic mutational constraint map using variation in 76,156 human genomes
OPENALEX - Publications 
Siwei Chen Laurent C. Francioli Julia K. Goodrich Ryan L. Collins Masahiro Kanai and 95 more Qingbo Wang Jessica Alföldi Nicholas A. Watts Christopher Vittal Laura D. Gauthier Timothy Poterba Michael W. Wilson Yekaterina Tarasova William Phu Riley Grant Mary T. Yohannes Zan Koenig Yossi Farjoun Eric Banks Stacey Donnelly Stacey Gabriel Namrata Gupta Steven Ferriera Charlotte Tolonen Sam Novod Louis Bergelson David Roazen Valentín Ruano-Rubio Miguel Covarrubias Christopher Llanwarne Nikelle Petrillo Gordon Wade Thibault Jeandet Ruchi Munshi Kathleen Tibbetts María T. Abreu Carlos A. Aguilar‐Salinas Tariq Ahmad Christine M. Albert Diego Ardissino Irina M. Armean Elizabeth G. Atkinson Gil Atzmon John Barnard Samantha Baxter Laurent Beaugerie Emelia J. Benjamin David Benjamin Michael Boehnke Lori L. Bonnycastle Erwin P. Böttinger Donald W. Bowden Matthew J. Bown Harrison Brand Steven R. Brant Ted Brookings Sam Bryant Sarah E. Calvo Hannia Campos John C. Chambers Juliana C.N. Chan Katherine R. Chao Sinéad B. Chapman Daniel I. Chasman Rex L. Chisholm Judy H. Cho Rajiv Chowdhury Mina K. Chung Wendy K. Chung Kristian Cibulskis Bruce M. Cohen Kristen M. Connolly Adolfo Correa Beryl B. Cummings Dana Dabelea John Danesh Dawood Darbar Phil Darnowsky Joshua C. Denny Ravindranath Duggirala Josée Dupuis Patrick T. Ellinor Roberto Elosúa James Emery Eleina England Jeanette Erdmann Tõnu Esko Emily Evangelista Diane Fatkin José C. Florez André Franke Jack Fu Martti Färkkilâ Kiran Garimella Jeff Gentry Gad Getz David C. Glahn Benjamin Gläser Stephen J. Glatt David B. Goldstein

10.1038/s41586-023-06045-0 article EN Nature 2023-12-06
 Low Incidence of Off-Target Mutations in Individual CRISPR-Cas9 and TALEN Targeted Human Stem Cell Clones Detected by Whole-Genome Sequencing
OPENALEX - Publications 
Adrian Veres Bridget S. Gosis Qiurong Ding Ryan L. Collins Ashok Ragavendran and 5 more Harrison Brand Serkan Erdin Chad A. Cowan Michael E. Talkowski Kiran Musunuru

10.1016/j.stem.2014.04.020 article EN publisher-specific-oa Cell stem cell 2014-07-01
 Efficient Ablation of Genes in Human Hematopoietic Stem and Effector Cells using CRISPR/Cas9
OPENALEX - Publications 
Pankaj Kumar Mandal Leonardo M. R. Ferreira Ryan L. Collins Torsten Meißner Christian L. Boutwell and 12 more Max Friesen Vladimir Vrbanac Brian S. Garrison Alexei Stortchevoi David Bryder Kiran Musunuru Harrison Brand Andrew M. Tager Todd M. Allen Michael E. Talkowski Derrick J. Rossi Chad A. Cowan

10.1016/j.stem.2014.10.004 article EN publisher-specific-oa Cell stem cell 2014-11-01
 Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder
OPENALEX - Publications 
Joon‐Yong An Kevin Lin Lingxue Zhu Donna M. Werling Shan Dong and 30 more Harrison Brand Harold Z. Wang Xuefang Zhao Grace Schwartz Ryan L. Collins Benjamin Currall Claudia Dastmalchi Jeanselle Dea Clif Duhn Michael C. Gilson Lambertus Klei Lindsay Liang Eirene Markenscoff-Papadimitriou Sirisha Pochareddy Nadav Ahituv Joseph D. Buxbaum Hilary Coon Mark J. Daly Young S. Kim Gábor Marth Benjamin M. Neale Aaron R. Quinlan John L.R. Rubenstein Nenad Šestan Matthew W. State A. Jeremy Willsey Michael E. Talkowski Bernie Devlin Kathryn Roeder Stephan Sanders

INTRODUCTION The DNA of protein-coding genes is transcribed into mRNA, which translated proteins. “coding genome” describes the that contains information to make these proteins and represents ~1.5% human genome. Newly arising de novo mutations (variants observed in a child but not either parent) coding genome contribute numerous childhood developmental disorders, including autism spectrum disorder (ASD). Discovery effects aided by triplet code enables functional impact many be readily...

10.1126/science.aat6576 article EN Science 2018-12-14
 The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies
OPENALEX - Publications 
Claire Redin Harrison Brand Ryan L. Collins Tammy Kammin Elyse Mitchell and 95 more Jennelle C. Hodge Carrie Hanscom Vamsee Pillalamarri Catarina M. Seabra Mary‐Alice Abbott Omar Abdul‐Rahman Erika Aberg Rhett Adley Sofía Lizeth Alcaráz‐Estrada Fowzan S. Alkuraya Yu An MaryAnne Anderson Caroline Antolik Kwame Anyane‐Yeboa Joan Atkin Tina M. Bartell Jonathan A. Bernstein Elizabeth Beyer Ian Blumenthal Ernie M.H.F. Bongers Eva H. Brilstra Chester Brown Hennie T. Brüggenwirth Bert Callewaert Colby Chiang Ken Corning Helen Cox Edwin Cuppen Benjamin Currall Tom Cushing D. David Matthew A. Deardorff Annelies Dheedene Marc D’Hooghe Bert B.A. de Vries Dawn Earl Heather Ferguson Heather Fisher David Fitzpatrick Pamela Gerrol Daniela Giachino Joseph Glessner Troy J. Gliem Margo Grady Brett H. Graham Cristin Griffis Karen W. Gripp Andrea Gropman Andrea Hanson‐Kahn David J. Harris Mark A. Hayden R. Sean Hill Ron Hochstenbach Jodi D. Hoffman Robert J. Hopkin Monika Weisz Hubshman A. Micheil Innes Mira Irons Melita Irving Jessie C. Jacobsen Sandra Janssens Tamison Jewett John P. Johnson Marjolijn C.J. Jongmans Stephen G. Kahler David A. Koolen Jerome Korzelius Peter M. Kroisel Yves Lacassie William Lawless Emmanuelle Lemyre Kathleen A. Leppig Alex V. Levin Haibo Li Hong Li Eric C. Liao Cynthia Lim Edward J. Lose Diane Lucente Michael J. Macera Poornima Manavalan Giorgia Mandrile Carlo Marcelis Lauren Margolin Tamara Mason Diane Masser‐Frye Michael McClellan Cinthya J. Zepeda Mendoza Björn Menten Sjors Middelkamp Liya Regina Mikami Emily Moe Shehla Mohammed Tarja Mononen Megan Mortenson

10.1038/ng.3720 article EN Nature Genetics 2016-11-14
 An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder
OPENALEX - Publications 
Donna M. Werling Harrison Brand Joon‐Yong An Matthew R. Stone Lingxue Zhu and 42 more Joseph Glessner Ryan L. Collins Shan Dong Ryan M. Layer Eirene Markenscoff-Papadimitriou Andrew Farrell Grace Schwartz Harold Z. Wang Benjamin Currall Xuefang Zhao Jeanselle Dea Clif Duhn Carolyn A. Erdman Michael C. Gilson Rachita Yadav Robert E. Handsaker Seva Kashin Lambertus Klei Jeffrey D. Mandell Tomasz J. Nowakowski Yuwen Liu Sirisha Pochareddy Louw Smith Michael F. Walker Matthew J. Waterman Xin He Arnold R. Kriegstein John L.R. Rubenstein Nenad Šestan Steven A. McCarroll Benjamin M. Neale Hilary Coon A. Jeremy Willsey Joseph D. Buxbaum Mark J. Daly Matthew W. State Aaron R. Quinlan Gábor Marth Kathryn Roeder Bernie Devlin Michael E. Talkowski Stephan Sanders

10.1038/s41588-018-0107-y article EN Nature Genetics 2018-04-25
 A genome-wide mutational constraint map quantified from variation in 76,156 human genomes
OPENALEX - Publications 
Siwei Chen Laurent C. Francioli Julia K. Goodrich Ryan L. Collins Masahiro Kanai and 40 more Qingbo Wang Jessica Alföldi Nicholas A. Watts Christopher Vittal Laura D. Gauthier Timothy Poterba Michael W. Wilson Yekaterina Tarasova William Phu Mary T. Yohannes Zan Koenig Yossi Farjoun Eric Banks Stacey Donnelly Stacey Gabriel Namrata Gupta Steven Ferriera Charlotte Tolonen Sam Novod Louis Bergelson David Roazen Valentín Ruano-Rubio Miguel Covarrubias Christopher Llanwarne Nikelle Petrillo Gordon Wade Thibault Jeandet Ruchi Munshi Kathleen Tibbetts Anne O’Donnell‐Luria Matthew Solomonson Cotton Seed Alicia R. Martin Michael E. Talkowski Heidi L. Rehm Mark J. Daly Grace Tiao Benjamin M. Neale Daniel G. MacArthur Konrad J. Karczewski

Abstract The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders, but attempts assess constraint for non-protein-coding regions have proven more difficult. Here we aggregate, process, and release a dataset 76,156 genomes from the Genome Aggregation Database (gnomAD), largest public open-access genome reference dataset, use this build mutational map whole genome. We present...

10.1101/2022.03.20.485034 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2022-03-21
 Whole-Genome Sequencing to Characterize Monogenic and Polygenic Contributions in Patients Hospitalized With Early-Onset Myocardial Infarction
OPENALEX - Publications 
Amit V. Khera Mark Chaffin Seyedeh M. Zekavat Ryan L. Collins Carolina Roselli and 18 more Pradeep Natarajan Judith H. Lichtman Gail D’Onofrio Jennifer A. Mattera Rachel P. Dreyer John A. Spertus Kent D. Taylor Bruce M. Psaty Stephen S. Rich Wendy S. Post Namrata Gupta Stacey Gabriel Eric S. Lander Yii‐Der Ida Chen Michael E. Talkowski Jerome I. Rotter Harlan M. Krumholz Sekar Kathiresan

Background: The relative prevalence and clinical importance of monogenic mutations related to familial hypercholesterolemia high polygenic score (cumulative impact many common variants) pathways for early-onset myocardial infarction remain uncertain. Whole-genome sequencing enables simultaneous ascertainment both each individual. Methods: We performed deep-coverage whole-genome 2081 patients from 4 racial subgroups hospitalized in the United States with (age ≤55 years) recruited a 2:1...

10.1161/circulationaha.118.035658 article EN Circulation 2019-01-17
 A cross-disorder dosage sensitivity map of the human genome
OPENALEX - Publications 
Ryan L. Collins Joseph Glessner Eleonora Porcu Maarja Lepamets Rhonda Brandon and 48 more Christopher Lauricella Lide Han Theodore Morley Lisa‐Marie Niestroj Jacob C. Ulirsch Selin Everett Daniel P. Howrigan Philip M. Boone Jack Fu Konrad J. Karczewski Georgios Kellaris Chelsea Lowther Diane Lucente Kiana Mohajeri Margit Nõukas Xander Nuttle Kaitlin E. Samocha Mi K. Trinh Farid Ullah Urmo Võsa Matthew E. Hurles Swaroop Aradhya Erica E. Davis Hilary K. Finucane James F. Gusella Aura Janze Nicholas Katsanis Ludmila Matyakhina Benjamin M. Neale D. B. Sanders Stephanie Warren Jennelle C. Hodge Dennis Lal Douglas M. Ruderfer Jeanne Meck Reedik Mägi Tõnu Esko Alexandre Reymond Zoltán Kutalik Hákon Hákonarson Shamil Sunyaev Harrison Brand Michael E. Talkowski Andres Metspalu Reedik Mägi Mari Nelis Lili Milani Tõnu Esko

10.1016/j.cell.2022.06.036 article EN publisher-specific-oa Cell 2022-08-01
 Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly
OPENALEX - Publications 
Tatsiana Aneichyk William T. Hendriks Rachita Yadav David Shin Dadi Gao and 40 more Christine A. Vaine Ryan L. Collins Aloysius Domingo Benjamin Currall Alexei Stortchevoi Trisha Multhaupt‐Buell Ellen B. Penney Lilian Cruz Jyotsna Dhakal Harrison Brand Carrie Hanscom Caroline Antolik Marisela Dy-Hollins Ashok Ragavendran Jason G. Underwood Stuart Cantsilieris Katherine M. Munson Evan E. Eichler Patrick Acuña Criscely L. Go Roland Dominic G. Jamora Raymond L. Rosales Deanna M. Church Stephen R. Williams Sarah Garcia Christine Klein Ulrich Müller Kirk C. Wilhelmsen H. T. Marc Timmers Yechiam Sapir Brian J. Wainger Daniel A. Henderson Naoto Ito Neil Weisenfeld David M. Jaffe Nutan Sharma Xandra O. Breakefield Laurie J. Ozelius D. Cristopher Bragg Michael E. Talkowski

10.1016/j.cell.2018.02.011 article EN publisher-specific-oa Cell 2018-02-01
 Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome
OPENALEX - Publications 
Ryan L. Collins Harrison Brand Claire Redin Carrie Hanscom Caroline Antolik and 25 more Matthew R. Stone Joseph Glessner Tamara Mason Giulia Pregno Naghmeh Dorrani Giorgia Mandrile Daniela Giachino Danielle Perrin Cole Walsh Michelle Cipicchio Maura Costello Alexei Stortchevoi Joon‐Yong An Benjamin Currall Catarina M. Seabra Ashok Ragavendran Lauren Margolin Julián A. Martínez-Agosto Diane Lucente Brynn Levy Stephan Sanders Ronald J. Wapner Fabiola Quintero‐Rivera Wigard P. Kloosterman Michael E. Talkowski

Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. We sequenced 689 participants with autism disorder (ASD) other developmental abnormalities construct a genome-wide map large SV. Using long-insert jumping libraries at 105X mean physical coverage linked-read whole-genome sequencing from 10X Genomics, we document seven major classes ~5 kb...

10.1186/s13059-017-1158-6 article EN cc-by Genome biology 2017-02-20
 Transcript expression-aware annotation improves rare variant interpretation
OPENALEX - Publications 
Beryl B. Cummings Konrad J. Karczewski Jack A. Kosmicki Eleanor G. Seaby Nicholas A. Watts and 95 more Moriel Singer‐Berk Jonathan M. Mudge Juha Karjalainen F. Kyle Satterstrom Anne O’Donnell‐Luria Timothy Poterba Cotton Seed Matthew Solomonson Jessica Alföldi Jessica Alföldi Irina M. Armean Eric Banks Louis Bergelson Kristian Cibulskis Ryan L. Collins Kristen M. Connolly Miguel Covarrubias Beryl B. Cummings Mark J. Daly Stacey Donnelly Yossi Farjoun Steven Ferriera Laurent C. Francioli Stacey Gabriel Laura D. Gauthier Jeff Gentry Namrata Gupta Thibault Jeandet Diane Kaplan Konrad J. Karczewski Kristen M. Laricchia Christopher Llanwarne Eric Vallabh Minikel Ruchi Munshi Benjamin M. Neale Sam Novod Anne O’Donnell‐Luria Nikelle Petrillo Timothy Poterba David Roazen Valentín Ruano-Rubio Andrea Saltzman Kaitlin E. Samocha Molly Schleicher Cotton Seed Matthew Solomonson José Soto Grace Tiao Kathleen Tibbetts Charlotte Tolonen Christopher Vittal Gordon Wade Arcturus Wang Qingbo Wang James S. Ware Nicholas A. Watts Ben Weisburd Nicola Whiffin Carlos A. Aguilar‐Salinas Tariq Ahmad Christine M. Albert Diego Ardissino Gil Atzmon John Barnard Laurent Beaugerie Emelia J. Benjamin Michael Boehnke Lori L. Bonnycastle Erwin P. Böttinger Donald W. Bowden Matthew J. Bown John C. Chambers Juliana C.N. Chan Daniel I. Chasman Judy H. Cho Mina K. Chung Bruce M. Cohen Adolfo Correa Dana Dabelea Mark J. Daly Dawood Darbar Ravindranath Duggirala Josée Dupuis Patrick T. Ellinor Roberto Elosúa Jeanette Erdmann Tõnu Esko Martti Färkkilâ José C. Florez André Franke Gad Getz Benjamin Gläser Stephen J. Glatt David Goldstein Clicerio González

Abstract The acceleration of DNA sequencing in samples from patients and population studies has resulted extensive catalogues human genetic variation, but the interpretation rare variants remains problematic. A notable example this challenge is existence disruptive dosage-sensitive disease genes, even apparently healthy individuals. Here, by manual curation putative loss-of-function (pLoF) haploinsufficient genes Genome Aggregation Database (gnomAD) 1 , we show that one explanation for...

10.1038/s41586-020-2329-2 article EN cc-by Nature 2020-05-27
 Evaluating drug targets through human loss-of-function genetic variation
OPENALEX - Publications 
Eric Vallabh Minikel Konrad J. Karczewski Hilary C. Martin Beryl B. Cummings Nicola Whiffin and 95 more Daniel R. Rhodes Jessica Alföldi Richard C. Trembath David A. van Heel Mark J. Daly Jessica Alföldi Irina M. Armean Eric Banks Louis Bergelson Kristian Cibulskis Ryan L. Collins Kristen M. Connolly Miguel Covarrubias Beryl B. Cummings Mark J. Daly Stacey Donnelly Yossi Farjoun Steven Ferriera Laurent C. Francioli Stacey Gabriel Laura D. Gauthier Jeff Gentry Namrata Gupta Thibault Jeandet Diane Kaplan Konrad J. Karczewski Kristen M. Laricchia Christopher Llanwarne Eric Vallabh Minikel Ruchi Munshi Benjamin M. Neale Sam Novod Anne O’Donnell‐Luria Nikelle Petrillo Timothy Poterba David Roazen Valentín Ruano-Rubio Andrea Saltzman Kaitlin E. Samocha Molly Schleicher Cotton Seed Matthew Solomonson José Soto Grace Tiao Kathleen Tibbetts Charlotte Tolonen Christopher Vittal Gordon Wade Arcturus Wang Qingbo Wang James S. Ware Nicholas A. Watts Ben Weisburd Nicola Whiffin Carlos A. Aguilar‐Salinas Tariq Ahmad Christine M. Albert Diego Ardissino Gil Atzmon J. A. Barnard Laurent Beaugerie Emelia J. Benjamin Michael Boehnke Lori L. Bonnycastle Erwin P. Böttinger Donald W. Bowden Matthew J. Bown John C. Chambers Juliana C.N. Chan Daniel I. Chasman Judy H. Cho Mina K. Chung Bruce M. Cohen Adolfo Correa Dana Dabelea Mark J. Daly Dawood Darbar Ravindranath Duggirala Josée Dupuis Patrick T. Ellinor Roberto Elosúa Jeanette Erdmann Tõnu Esko Martti Färkkilâ José C. Florez André Franke Gad Getz Benjamin Gläser Stephen J. Glatt David Goldstein Clicerio González Per‐Henrik Groop Christopher Haiman Craig L. Hanis Matthew Harms

Abstract Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of gene inactivation complements knockout studies cells and organisms. Here we report three key findings regarding the assessment candidate drug targets using loss-of-function variants. First, even essential genes, which not tolerated, can be highly successful as inhibitory drugs. Second, most sufficiently rare genotype-based ascertainment homozygous or compound...

10.1038/s41586-020-2267-z article EN cc-by Nature 2020-05-27
 GATK-gCNV enables the discovery of rare copy number variants from exome sequencing data
OPENALEX - Publications 
Mehrtash Babadi Jack Fu Samuel K. Lee Andrey N. Smirnov Laura D. Gauthier and 10 more Mark Walker David Benjamin Xuefang Zhao Konrad J. Karczewski Isaac Wong Ryan L. Collins Alba Sanchis‐Juan Harrison Brand Eric Banks Michael E. Talkowski

10.1038/s41588-023-01449-0 article EN Nature Genetics 2023-08-21
 Loss of δ-catenin function in severe autism
OPENALEX - Publications 
Tychele N. Turner Kamal Sharma Edwin C. Oh Yangfan P. Liu Ryan L. Collins and 18 more Maria X. Sosa Dallas R. Auer Harrison Brand Stephan Sanders Daniel Moreno‐De‐Luca Vasyl Pihur Teri M. Plona Kristen Pike Daniel Soppet Michael W. Smith Sau Wai Cheung Christa Lese Martin Matthew W. State Michael E. Talkowski Edwin H. Cook Richard L. Huganir Nicholas Katsanis Aravinda Chakravarti

10.1038/nature14186 article EN Nature 2015-03-24
 SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
OPENALEX - Publications 
Natalie D. Shaw Harrison Brand Zachary A Kupchinsky Hemant Bengani Lacey Plummer and 73 more Takako I. Jones Serkan Erdin Kathleen A. Williamson Joe Rainger Alexei Stortchevoi Kaitlin E. Samocha Benjamin Currall Donncha S. Dunican Ryan L. Collins Jason R. Willer Angela Lek Monkol Lek Malik Nassan Shahrin Pereira Tammy Kammin Diane Lucente Alexandra Silva Catarina M. Seabra Colby Chiang Yu An Morad Ansari Jacqueline K. Rainger Shelagh Joss Jill Smith Margaret Lippincott Sylvia Singh Nirav Patel Jenny W Jing Jennifer Law Nalton Ferraro Alain Verloès Anita Rauch Katharina Steindl Markus Zweier Ianina Scheer Daisuke Sato Nobuhiko Okamoto Christina M. Jacobsen Jeanie B. Tryggestad Steven D. Chernausek Lisa A. Schimmenti Benjamin Brasseur Claudia Cesaretti José Elías García‐Ortíz Tatiana Pineda Buitrago Orlando Pérez Silva Jodi D. Hoffman W. Mühlbauer Klaus W. Ruprecht Bart Loeys Masato Shino Angela M. Kaindl Chie Hee Cho Cynthia C. Morton Richard R. Meehan Veronica van Heyningen Eric C. Liao Ravikumar Balasubramanian Janet E. Hall Stephanie B. Seminara Daniel G. MacArthur Steven A. Moore Koh-ichiro Yoshiura James F. Gusella Joseph A. Marsh John M. Graham Angela E. Lin Nicholas Katsanis Peter L. Jones William F. Crowley Erica E. Davis David Fitzpatrick Michael E. Talkowski

10.1038/ng.3743 article EN Nature Genetics 2017-01-09
 Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals
OPENALEX - Publications 
Nicola Whiffin Konrad J. Karczewski Xiaolei Zhang Sonia Chothani Miriam J. Smith and 95 more D. Gareth Evans Angharad M. Roberts Nicholas M. Quaife Sebastian Schäfer Owen J. L. Rackham Jessica Alföldi Anne O’Donnell‐Luria Laurent C. Francioli Irina M. Armean Eric Banks Louis Bergelson Kristian Cibulskis Ryan L. Collins Kristen M. Connolly Miguel Covarrubias Beryl B. Cummings Mark J. Daly Stacey Donnelly Yossi Farjoun Steven Ferriera Stacey Gabriel Laura D. Gauthier Jeff Gentry Namrata Gupta Thibault Jeandet Diane Kaplan Kristen M. Laricchia Christopher Llanwarne Eric Vallabh Minikel Ruchi Munshi Benjamin M. Neale Sam Novod Nikelle Petrillo Timothy Poterba David Roazen Valentín Ruano-Rubio Andrea Saltzman Kaitlin E. Samocha Molly Schleicher Cotton Seed Matthew Solomonson José Soto Grace Tiao Kathleen Tibbetts Charlotte Tolonen Christopher Vittal Gordon Wade Arcturus Wang Qingbo Wang Nicholas A. Watts Ben Weisburd Carlos A. Aguilar‐Salinas Tariq Ahmad Christine M. Albert Diego Ardissino Gil Atzmon John Barnard Laurent Beaugerie Emelia J. Benjamin Michael Boehnke Lori L. Bonnycastle Erwin P. Böttinger Donald W. Bowden Matthew J. Bown John C. Chambers Juliana C.N. Chan Daniel I. Chasman Judy H. Cho Mina K. Chung Bruce M. Cohen Adolfo Correa Dana Dabelea Mark J. Daly Dawood Darbar Ravindranath Duggirala Josée Dupuis Patrick T. Ellinor Roberto Elosúa Jeanette Erdmann Tõnu Esko Martti Färkkilâ José C. Florez André Franke Gad Getz Benjamin Gläser Stephen J. Glatt David Goldstein Clicerio González Leif Groop Christopher Haiman Craig L. Hanis Matthew B. Harms Mikko Hiltunen Matti Holi Christina M. Hultman

Upstream open reading frames (uORFs) are tissue-specific cis-regulators of protein translation. Isolated reports have shown that variants create or disrupt uORFs can cause disease. Here, in a systematic genome-wide study using 15,708 whole genome sequences, we show new upstream start codons, and disrupting stop sites existing uORFs, under strong negative selection. This selection signal is significantly stronger for arising genes intolerant to loss-of-function variants. Furthermore, creating...

10.1038/s41467-019-10717-9 article EN cc-by Nature Communications 2020-05-27
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