title: The Influence of Microdeletions and Microduplications of 16p11.2 on Global Transcription Profiles.
abstract: Copy number variants (CNVs) of a 600 kb region on 16p11.2 are associated with neurodevelopmental disorders and changes in brain volume. The authors hypothesize that abnormal brain development associated with this CNV can be attributed to changes in transcriptional regulation. The authors determined the effects of 16p11.2 dosage on gene expression by transcription profiling of lymphoblast cell lines derived from 6 microdeletion carriers, 15 microduplication carriers and 15 controls. Gene dosage had a significant influence on the transcript abundance of a majority (20/34) of genes within the CNV region. In addition, a limited number of genes were dysregulated in trans. Genes most strongly correlated with patient head circumference included SULT1A, KCTD13, and TMEM242. Given the modest effect of 16p11.2 copy number on global transcriptional regulation in lymphocytes, larger studies utilizing neuronal cell types may be needed in order to elucidate the signaling pathways that influence brain development in this genetic disorder.
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA Department of Biology, Chemistry and Environmental Studies, Molloy College, Rockville Centre, New York 11571, USA Current affiliation.
authors.forename: Mary
authors.initials: M
authors.lastname: Kusenda
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vacic
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry, and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Malhotra
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Rodgers
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pavon
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Meth
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: Ravinesh A
authors.initials: RA
authors.lastname: Kumar
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Christian
authors.affiliation: Laboratory for Genetics of Human Development, Department of Human Genetics, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Netherlands.
authors.forename: Hilde
authors.initials: H
authors.lastname: Peeters
authors.affiliation: Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry, and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Shawn S
authors.initials: SS
authors.lastname: Cho
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Anjene
authors.initials: A
authors.lastname: Addington
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.affiliation: Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry, and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA jsebat@ucsd.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sebat
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002885:Chromosomes, Human, Pair 16; D056915:DNA Copy Number Variations; D020440:Gene Duplication; D015870:Gene Expression / Q000235:genetics; D006257:Head / Q000473:pathology; D004854:Herpesvirus 4, Human; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D046228:Microarray Analysis; D009929:Organ Size; D060888:Real-Time Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion; D059467:Transcriptome / Q000235:genetics*
keywords: 16p11.2; autism spectrum disorders (ASD); copy number variation (CNV); gene expression; schizophrenia (SCZ)