David E Root

David E Root

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David E Root

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Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers.

Cell Rep 2019 Oct;29(1):118-134.e8

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, MA. Electronic address:

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http://dx.doi.org/10.1016/j.celrep.2019.08.090DOI Listing
October 2019

A Functional Landscape of Resistance to MEK1/2 and CDK4/6 Inhibition in NRAS-Mutant Melanoma.

Cancer Res 2019 May 28;79(9):2352-2366. Epub 2019 Feb 28.

Cancer Program, The Broad Institute of M.I.T. and Harvard, Cambridge, Massachusetts.

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2711DOI Listing
May 2019

DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells.

Nature 2018 11 31;563(7732):522-526. Epub 2018 Oct 31.

Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1038/s41586-018-0670-5DOI Listing
November 2018

Regulation of Cellular Heterogeneity and Rates of Symmetric and Asymmetric Divisions in Triple-Negative Breast Cancer.

Cell Rep 2018 09;24(12):3237-3250

Department of Developmental Biology and Cancer Research, Institute for Medical Research-Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S22111247183133
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http://dx.doi.org/10.1016/j.celrep.2018.08.053DOI Listing
September 2018

Nitric Oxide Engages an Anti-inflammatory Feedback Loop Mediated by Peroxiredoxin 5 in Phagocytes.

Cell Rep 2018 07;24(4):838-850

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02114, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:

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http://dx.doi.org/10.1016/j.celrep.2018.06.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156773PMC
July 2018

Pooled Lentiviral-Delivery Genetic Screens.

Curr Protoc Mol Biol 2018 01 16;121:32.1.1-32.1.21. Epub 2018 Jan 16.

Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

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http://dx.doi.org/10.1002/cpmb.52DOI Listing
January 2018

Defining a Cancer Dependency Map.

Cell 2017 Jul;170(3):564-576.e16

Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA, USA; Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cell.2017.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667678PMC
July 2017

CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors.

Cell Host Microbe 2017 May;21(5):580-591.e7

Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

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http://dx.doi.org/10.1016/j.chom.2017.04.005DOI Listing
May 2017

Complementary information derived from CRISPR Cas9 mediated gene deletion and suppression.

Nat Commun 2017 05 23;8:15403. Epub 2017 May 23.

Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA.

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http://dx.doi.org/10.1038/ncomms15403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457492PMC
May 2017

PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA.

Nat Commun 2017 04 27;8:15110. Epub 2017 Apr 27.

Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.

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http://dx.doi.org/10.1038/ncomms15110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414184PMC
April 2017

A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation.

Cell Metab 2016 12 22;24(6):875-885. Epub 2016 Sep 22.

Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

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http://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30433-
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http://www.cell.com/cms/attachment/2064501967/2065983246/mmc
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http://dx.doi.org/10.1016/j.cmet.2016.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474757PMC
December 2016

High-Throughput Platform for Identifying Molecular Factors Involved in Phenotypic Stabilization of Primary Human Hepatocytes In Vitro.

J Biomol Screen 2016 Oct 4;21(9):897-911. Epub 2016 Aug 4.

Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA The Broad Institute of MIT and Harvard, Cambridge, MA, USA Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA Institute for Medical Engineering and Science, MIT, Cambridge, MA, USA Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA Howard Hughes Medical Institute, Chevy Chase, MD, USA

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http://dx.doi.org/10.1177/1087057116660277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352718PMC
October 2016

Bromodomain Inhibitors Correct Bioenergetic Deficiency Caused by Mitochondrial Disease Complex I Mutations.

Mol Cell 2016 10 22;64(1):163-175. Epub 2016 Sep 22.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA 02215; Department of Cell Biology, Harvard Medical School, Boston, MA, USA 02215; Broad Institute of MIT and Harvard, Cambridge, MA, USA 02142. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S10972765163046
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055448PMC
http://dx.doi.org/10.1016/j.molcel.2016.08.023DOI Listing
October 2016

Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in β-Catenin-Active Cancers.

Cell Syst 2016 09;3(3):302-316.e4

Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cels.2016.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455996PMC
September 2016

Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting.

Cancer Discov 2016 08 3;6(8):914-29. Epub 2016 Jun 3.

Dana-Farber Cancer Institute, Boston, Massachusetts. Broad Institute of Harvard and MIT, Cambridge, Massachusetts. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.

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http://dx.doi.org/10.1158/2159-8290.CD-16-0154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972686PMC
August 2016

Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies.

Sci Data 2014 30;1:140035. Epub 2014 Sep 30.

Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA ; Department of Medical, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA ; Center for Cancer Genome Discovery, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA ; Departments of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, USA.

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http://www.nature.com/articles/sdata201435
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http://dx.doi.org/10.1038/sdata.2014.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432652PMC
February 2016

Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors.

Mol Cancer Ther 2015 Dec 8;14(12):2700-11. Epub 2015 Sep 8.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. The Broad Institute, Cambridge, Massachusetts. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1158/1535-7163.MCT-15-0136-TDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674359PMC
December 2015

Resources for the design of CRISPR gene editing experiments.

Genome Biol 2015 Nov 27;16:260. Epub 2015 Nov 27.

Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

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http://genomebiology.com/2015/16/1/260
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http://dx.doi.org/10.1186/s13059-015-0823-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661947PMC
November 2015

Identification of an oncogenic RAB protein.

Science 2015 Oct 3;350(6257):211-7. Epub 2015 Sep 3.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

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http://sabatinilab.wi.mit.edu/pubs/2013/Science-2015-Wheeler
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http://www.sciencemag.org/cgi/doi/10.1126/science.aaa4903
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http://dx.doi.org/10.1126/science.aaa4903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600465PMC
October 2015

The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity.

Nat Immunol 2015 May 6;16(5):495-504. Epub 2015 Apr 6.

Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.

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http://dx.doi.org/10.1038/ni.3143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406861PMC
May 2015

Synthetic lethal screening in the mammalian central nervous system identifies Gpx6 as a modulator of Huntington's disease.

Proc Natl Acad Sci U S A 2015 Jan 22;112(1):268-72. Epub 2014 Dec 22.

The Broad Institute of MIT and Harvard University, Cambridge, MA 02142; The Picower Institute for Learning and Memory, Cambridge, MA 02139; and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139

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http://dx.doi.org/10.1073/pnas.1417231112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291668PMC
January 2015

Inducible RNAi in vivo reveals that the transcription factor BATF is required to initiate but not maintain CD8+ T-cell effector differentiation.

Proc Natl Acad Sci U S A 2015 Jan 29;112(2):512-7. Epub 2014 Dec 29.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; Broad Institute of MIT and Harvard, Cambridge, MA 02142; Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA 02115

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http://dx.doi.org/10.1073/pnas.1413291112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299213PMC
January 2015

Genetic modifiers of EGFR dependence in non-small cell lung cancer.

Proc Natl Acad Sci U S A 2014 Dec 15;111(52):18661-6. Epub 2014 Dec 15.

Broad Institute of Harvard and MIT, Cambridge, MA 02142; Departments of Pathology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; and

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http://dx.doi.org/10.1073/pnas.1412228112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284598PMC
December 2014

Targeted shRNA screening identified critical roles of pleckstrin-2 in erythropoiesis.

Haematologica 2014 Jul 18;99(7):1157-67. Epub 2014 Apr 18.

Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL

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http://dx.doi.org/10.3324/haematol.2014.105809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077076PMC
July 2014

Requirement for CDK6 in MLL-rearranged acute myeloid leukemia.

Blood 2014 Jul 24;124(1):13-23. Epub 2014 Apr 24.

Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany; German Consortium for Translational Cancer Research, Heidelberg, Germany;

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http://dx.doi.org/10.1182/blood-2014-02-558114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190617PMC
July 2014

KRAS and YAP1 converge to regulate EMT and tumor survival.

Cell 2014 Jul 19;158(1):171-84. Epub 2014 Jun 19.

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cell.2014.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110062PMC
July 2014

An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia.

Nat Genet 2014 Apr 2;46(4):364-70. Epub 2014 Mar 2.

1] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3] Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [4] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.

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http://www.nature.com/articles/ng.2913
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http://dx.doi.org/10.1038/ng.2913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086945PMC
April 2014

Genome-scale CRISPR-Cas9 knockout screening in human cells.

Science 2014 Jan 12;343(6166):84-87. Epub 2013 Dec 12.

Broad Institute of MIT and Harvard, 7 Cambridge Center, MA 02142, USA.

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http://dx.doi.org/10.1126/science.1247005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089965PMC
January 2014

An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription.

Proc Natl Acad Sci U S A 2014 Jan 16;111(4):1491-6. Epub 2014 Jan 16.

Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.

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http://dx.doi.org/10.1073/pnas.1323535111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910647PMC
January 2014

ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state.

Cell Rep 2014 Jan 16;6(2):313-24. Epub 2014 Jan 16.

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

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http://dx.doi.org/10.1016/j.celrep.2013.12.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041390PMC
January 2014

A melanocyte lineage program confers resistance to MAP kinase pathway inhibition.

Nature 2013 Dec 3;504(7478):138-42. Epub 2013 Nov 3.

1] The Broad Institute of Harvard University and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.

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http://dx.doi.org/10.1038/nature12688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098832PMC
December 2013

SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer.

Cancer Cell 2013 Dec;24(6):738-50

Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ccr.2013.10.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910168PMC
December 2013

Receptor tyrosine kinases fall into distinct classes based on their inferred signaling networks.

Sci Signal 2013 Jul 16;6(284):ra58. Epub 2013 Jul 16.

Department of Chemistry & Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.

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http://dx.doi.org/10.1126/scisignal.2003994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3987808PMC
July 2013

The ANK3 bipolar disorder gene regulates psychiatric-related behaviors that are modulated by lithium and stress.

Biol Psychiatry 2013 Apr 11;73(7):683-90. Epub 2012 Dec 11.

Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, USA.

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http://dx.doi.org/10.1016/j.biopsych.2012.10.016DOI Listing
April 2013