An emerging molecular “parts list” for schizophrenia

Slides:



Advertisements
Similar presentations
Manolis Kellis Broad Institute of MIT and Harvard
Advertisements

Chapter 10 Molecular Diagnosis. Keypoints Identification of the gene for a disorder permits diagnostic testing by direct mutation analysis. Some genetic.
What does it take to detect risk genes for psychiatric disorders?
Clinical Neuroscience Second Edition Chapter 9: Mood Disorders Kelly Lambert and Craig Howard Kinsley Copyright © 2011 by Oxford University Press, Inc.
Illustration of how the diagnostic yield changes as the size of the gene panel (number of genes) increases. The general characteristics of panels of various.
Transverse illustration of the upper abdomen that demonstrates the dependent compartments where free intraperitoneal fluid may collect (A). A transverse.
Contrasting hypotheses of genomic imprinting in cancer
(Adapted, with permission, from Fagin JA
Mutations in the retinoblastoma tumor-suppressor gene (RB1) contribute to inherited and sporadic cancers. The figure indicates that cell context affects.
Approach to hypernatremia
Structure of the A-subunit gene and identified mutations
(Reprinted by permission from Macmillan Publishers Ltd
Proposed sites of action of current multiple sclerosis (MS) treatments
Upregulation of the cAMP pathway as a mechanism of opiate tolerance and dependence. Opiates acutely inhibit the functional activity of the cAMP pathway.
Prototypical eukaryotic gene
Communication strategy: increasing mammogram use
Limbic regions involved in emotion and mood. A
Neural reward circuits for various drugs (cocaine, amphetamines, opiates, nicotine, and ethanol) in a sagittal section of rat brain. A limbic–extrapyramidal.
Hypothetical mechanism of ketamine’s antidepressant effects
More complex considerations of receptor signaling. A
[From Pansky B: Review of Gross Anatomy, 6th ed
Ca2+ and phosphatidylinositol second messenger systems
Activation of protein kinases. A
Midsagittal section through the brain of a patient with a brain stem tumor. Histologic findings showed the tumor to be an ependymoma. Source: Discussion.
Proteins involved in muscular dystrophies
Model accounting for the mechanisms linking epipodophyllotoxin therapy, MLL fusion proteins, cell cycle progression, and the relaxation of cell cycle checkpoints,
Contrasting hypotheses of genomic imprinting in cancer
Evolution of the ubiquitous α-, β-, and γ-crystallins and their structure. Details are described in the text. The α-crystallins are related to heat-shock.
Depiction of meiotic crossing over and linkage analysis
Illustration of ways regression lines can differ
Ultrasound image of the large internal jugular vein and deeper carotid artery. Transducer position (A) and corresponding ultrasound image (B). CA = Carotid.
Regulation of gating in ion channels
(Adapted and reprinted with permission, from Hughes JM et al: Effect of lung volume on the distribution of pulmonary blood flow in man. Respir Physiol.
The processing of microRNA that is involved in gene regulation by RNA interference. (Reprinted with permission from Brooker RJ: Genetics: Analysis & Principles,
Decision tree for ulcerative colitis
Adapted with permission from Hsia, J et al
Array technology permits simultaneous quantification of dozens to millions of analytes. In the array-based rtPCR panel depicted here, RNA is extracted.
Adult basic life support health care provider algorithm
MRI contrast-enhancement and progression of X-ALD
This defibrillator device has been set to synchronized “SYNC” mode
Internal hemorrhoids. (Used, with permission, from John Cello, MD.)
Down syndrome (DS) critical region
Molecular testing for the trinucleotide repeats in fragile X syndrome
Hierarchy of clinical evidence
(b) Higher magnification shows the relationship of the many rounded, thin-walled alveoli (A) to alveolar ducts (AD). Alveolar ducts end in two or more.
The effects of apo E alleles on various lipoprotein parameters
[From: Galli : et al: Emergency Orthopedics: The Spine
Basic algorithm for cancer risk assessment that employs gene testing.
(Reproduced, with permission, from Fulop M, et al
Color Doppler of right kidney—longitudinal views
Chapter 3 Image Slides Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Schizophrenia and Affective Disorders—Cosegregation with a Translocation at Chromosome 1q42 That Directly Disrupts Brain-Expressed Genes: Clinical and.
Transmission of Action Potential Across a Synapse
Copyright © 2004 The McGraw-Hill Companies, Inc. All rights reserved.
Psychiatric Disorders: Diagnosis to Therapy
Mutations Chapter 9.
Neuroscience of Addiction
Copyright © 2004 The McGraw-Hill Companies, Inc. All rights reserved.
The Challenges and Promise of Neuroimaging in Psychiatry
Volume 68, Issue 2, Pages (October 2010)
Steven A. McCarroll, Steven E. Hyman  Neuron 
Copyright © 2004 The McGraw-Hill Companies, Inc. All rights reserved.
Volume 70, Issue 5, Pages (June 2011)
Psychiatric Disorders: Diagnosis to Therapy
Joshua W. Buckholtz, Andreas Meyer-Lindenberg  Neuron 
Copyright © 2004 The McGraw-Hill Companies, Inc. All rights reserved.
The Role of Neuronal Complexes in Human X-Linked Brain Diseases
Copyright © 2004 The McGraw-Hill Companies, Inc. All rights reserved.
Copyright © 2013 Elsevier Inc. All rights reserved.
Copyright © 2013 Elsevier Inc. All rights reserved.
Presentation transcript:

An emerging molecular “parts list” for schizophrenia An emerging molecular “parts list” for schizophrenia. Analysis of both common and rare genetic variants associated with schizophrenia is beginning to yield an initial list of proteins that appear to be associated with risk. Most common risk-associated variants likely affect levels of gene expression, while rare variants within exons may influence protein function. Shown here is an α1 subunit of the L-type Ca2+ channel (encoded by CACNA1C), which forms a pore, and a β subunit (eg, encoded by CACNB2), which is regulatory. Functioning channels include additional regulatory subunits (depicted by orange oval). A common variant linked to CACNA1C is among the most strongly associated risk alleles for both schizophrenia and bipolar disorder; common variants within CACNB2 are strongly associated not only with schizophrenia but also with risk for several other psychiatric disorders. In addition, both common and rare variants associated with schizophrenia cluster in postsynaptic specializations of excitatory synapses (see 5–1 in Chapter 5). (Adapted with permission from McCarroll SA, Hyman SE. Progress in the genetics of polygenic brain disorders: significant challenges for neurobiology. Neuron. 2013;80(3):578–587.) Source: Schizophrenia and Bipolar Disorder, Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e Citation: Nestler EJ, Hyman SE, Holtzman DM, Malenka RC. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e; 2015 Available at: https://neurology.mhmedical.com/DownloadImage.aspx?image=/data/books/1204/nes003_fig_17-03.png&sec=72650667&BookID=1204&ChapterSecID=72650640&imagename= Accessed: December 27, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved