Disentangling the Role of SHANK1 in a Mouse Model for Autism Spectrum Disorder: from Brain to Behavior
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Prevention Or Amelioration of Autism-Like Symptoms in Animal Models: Will It Bring Us Closer to Treating Human ASD?
International Journal of Molecular Sciences Review Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD? Asher Ornoy 1,* , Liza Weinstein-Fudim 1 and Zivanit Ergaz 1,2 1 Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel; [email protected] 2 Neonatology Department, Hadassah Hebrew University Medical Center, Jerusalem 9112001, Israel; [email protected] * Correspondence: [email protected]; Tel.: +972-2-6758329 Received: 17 February 2019; Accepted: 23 February 2019; Published: 1 March 2019 Abstract: Since the first animal model of valproic acid (VPA) induced autistic-like behavior, many genetic and non-genetic experimental animal models for Autism Spectrum Disorder (ASD) have been described. The more common non-genetic animal models induce ASD in rats and mice by infection/inflammation or the prenatal or early postnatal administration of VPA. Through the establishment of these models, attempts have been made to ameliorate or even prevent ASD-like symptoms. Some of the genetic models have been successfully treated by genetic manipulations or the manipulation of neurotransmission. Different antioxidants have been used (i.e., astaxanthin, green tea, piperine) to reduce brain oxidative stress in VPA-induced ASD models. Agents affecting brain neurotransmitters (donepezil, agmatine, agomelatine, memantine, oxytocin) also successfully reduced ASD-like symptoms. However, complete prevention of the development of symptoms was achieved only rarely. In our recent study, we treated mouse offspring exposed on postnatal day four to VPA with S-adenosine methionine (SAM) for three days, and prevented ASD-like behavior, brain oxidative stress, and the changes in gene expression induced by VPA. -
Kazlauskas, Nadia. 2017 03 17
Tesis Doctoral Alteraciones sexo-específicas en sociabilidad y neuroinflamación en un modelo en ratón de autismo Kazlauskas, Nadia 2017-03-17 Este documento forma parte de la colección de tesis doctorales y de maestría de la Biblioteca Central Dr. Luis Federico Leloir, disponible en digital.bl.fcen.uba.ar. Su utilización debe ser acompañada por la cita bibliográfica con reconocimiento de la fuente. This document is part of the doctoral theses collection of the Central Library Dr. Luis Federico Leloir, available in digital.bl.fcen.uba.ar. It should be used accompanied by the corresponding citation acknowledging the source. Cita tipo APA: Kazlauskas, Nadia. (2017-03-17). Alteraciones sexo-específicas en sociabilidad y neuroinflamación en un modelo en ratón de autismo. Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Cita tipo Chicago: Kazlauskas, Nadia. "Alteraciones sexo-específicas en sociabilidad y neuroinflamación en un modelo en ratón de autismo". Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. 2017-03-17. Dirección: Biblioteca Central Dr. Luis F. Leloir, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires. Contacto: [email protected] Intendente Güiraldes 2160 - C1428EGA - Tel. (++54 +11) 4789-9293 Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales Departamento de Fisiología, Biología Molecular y Celular Alteraciones sexo-específicas en sociabilidad y neuroinflamación en un modelo en ratón de autismo Tesis presentada para optar por el título de Doctor de la Universidad de Buenos Aires en el área Ciencias Biológicas Nadia Kazlauskas Directora de tesis: Dra. Amaicha Mara Depino Consejera de estudios: Dra. Lidia Szczupak Lugar de trabajo: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE-CONICET). -
Deciphering the Molecular Profile of Plaques, Memory Decline And
ORIGINAL RESEARCH ARTICLE published: 16 April 2014 AGING NEUROSCIENCE doi: 10.3389/fnagi.2014.00075 Deciphering the molecular profile of plaques, memory decline and neuron loss in two mouse models for Alzheimer’s disease by deep sequencing Yvonne Bouter 1†,Tim Kacprowski 2,3†, Robert Weissmann4, Katharina Dietrich1, Henning Borgers 1, Andreas Brauß1, Christian Sperling 4, Oliver Wirths 1, Mario Albrecht 2,5, Lars R. Jensen4, Andreas W. Kuss 4* andThomas A. Bayer 1* 1 Division of Molecular Psychiatry, Georg-August-University Goettingen, University Medicine Goettingen, Goettingen, Germany 2 Department of Bioinformatics, Institute of Biometrics and Medical Informatics, University Medicine Greifswald, Greifswald, Germany 3 Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany 4 Human Molecular Genetics, Department for Human Genetics of the Institute for Genetics and Functional Genomics, Institute for Human Genetics, University Medicine Greifswald, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany 5 Institute for Knowledge Discovery, Graz University of Technology, Graz, Austria Edited by: One of the central research questions on the etiology of Alzheimer’s disease (AD) is the Isidro Ferrer, University of Barcelona, elucidation of the molecular signatures triggered by the amyloid cascade of pathological Spain events. Next-generation sequencing allows the identification of genes involved in disease Reviewed by: Isidro Ferrer, University of Barcelona, processes in an unbiased manner. We have combined this technique with the analysis of Spain two AD mouse models: (1) The 5XFAD model develops early plaque formation, intraneu- Dietmar R. Thal, University of Ulm, ronal Ab aggregation, neuron loss, and behavioral deficits. (2)TheTg4–42 model expresses Germany N-truncated Ab4–42 and develops neuron loss and behavioral deficits albeit without plaque *Correspondence: formation. -
Supplementary Table 1. Mutated Genes That Contain Protein Domains Identified Through Mutation Enrichment Analysis
Supplementary Table 1. Mutated genes that contain protein domains identified through mutation enrichment analysis A. Breast cancers InterPro ID Mutated genes (number of mutations) IPR000219 ARHGEF4(2), ECT2(1), FARP1(1), FLJ20184(1), MCF2L2(1), NET1(1), OBSCN(5), RASGRF2(2), TRAD(1), VAV3(1) IPR000225 APC2(2), JUP(1), KPNA5(2), SPAG6(1) IPR000357 ARFGEF2(2), CMYA4(1), DRIM(2), JUP(1), KPNA5(2), PIK3R4(1), SPAG6(1) IPR000533 AKAP9(2), C10orf39(1), C20orf23(1), CUTL1(1), HOOK1(1), HOOK3(1), KTN1(2), LRRFIP1(3), MYH1(3), MYH9(2), NEF3(1), NF2(1), RSN(1), TAX1BP1(1), TPM4(1) IPR000694 ADAM12(3), ADAMTS19(1), APC2(2), APXL(1), ARID1B(1), BAT2(2), BAT3(1), BCAR1(1), BCL11A(2), BCORL1(1), C14orf155(3), C1orf2(1), C1QB(1), C6orf31(1), C7orf11(1), CD2(1), CENTD3(3), CHD5(3), CIC(3), CMYA1(2), COL11A1(3), COL19A1(2), COL7A1(3), DAZAP1(1), DBN1(3), DVL3(1), EIF5(1), FAM44A(1), FAM47B(1), FHOD1(1), FLJ20584(1), G3BP2(2), GAB1(2), GGA3(1), GLI1(3), GPNMB(2), GRIN2D(3), HCN3(1), HOXA3(2), HOXA4(1), IRS4(1), KCNA5(1), KCNC2(1), LIP8(1), LOC374955(1), MAGEE1(2), MICAL1(2), MICAL‐L1(1), MLLT2(1), MMP15(1), N4BP2(1), NCOA6(2), NHS(1), NUP214(3), ODZ1(3), PER1(2), PER2(1), PHC1(1), PLXNB1(1), PPM1E(2), RAI17(2), RAPH1(2), RBAF600(2), SCARF2(1), SEMA4G(1), SLC16A2(1), SORBS1(1), SPEN(2), SPG4(1), TBX1(1), TCF1(2), TCF7L1(1), TESK1(1), THG‐1(1), TP53(18), TRIF(1), ZBTB3(2), ZNF318(2) IPR000909 CENTB1(2), PLCB1(1), PLCG1(1) IPR000998 AEGP(3), EGFL6(2), PRSS7(1) IPR001140 ABCB10(2), ABCB6(1), ABCB8(2) IPR001164 ARFGAP3(1), CENTB1(2), CENTD3(3), CENTG1(2) IPR001589 -
Rare Gene Deletions in Genetic Generalized and Rolandic Epilepsies
RESEARCH ARTICLE Rare gene deletions in genetic generalized and Rolandic epilepsies Kamel Jabbari1,2☯, Dheeraj R. Bobbili3☯, Dennis Lal1,4,5,6, Eva M. Reinthaler7, Julian Schubert8, Stefan Wolking8, Vishal Sinha9, Susanne Motameny1, Holger Thiele1, Amit Kawalia1, Janine AltmuÈ ller1,10, Mohammad Reza Toliat1, Robert Kraaij11, Jeroen van Rooij11, Andre G. Uitterlinden11, M. Arfan Ikram12, EuroEPINOMICS CoGIE Consortium¶, Federico Zara13, Anna-Elina Lehesjoki14,15, Roland Krause3, Fritz Zimprich7, Thomas Sander1, Bernd A. Neubauer16, Patrick May3, Holger Lerche8, Peter NuÈrnberg1,17,18* a1111111111 1 Cologne Center for Genomics, University of Cologne, Cologne, Germany, 2 Cologne Biocenter, Institute a1111111111 for Genetics, University of Cologne, Cologne, Germany, 3 Luxembourg Centre for Systems Biomedicine, a1111111111 University of Luxembourg, Esch-sur-Alzette, Luxembourg, 4 Psychiatric and Neurodevelopmental Genetics a1111111111 Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of a1111111111 America, 5 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 6 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 7 Department of Neurology, Medical University of Vienna, Vienna, Austria, 8 Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of TuÈbingen, TuÈbingen, Germany, 9 Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland, 10 Institute of Human Genetics, University of Cologne, OPEN ACCESS Cologne, Germany, 11 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands, 12 Departments of Epidemiology, Neurology, and Radiology, Erasmus Medical Center, Citation: Jabbari K, Bobbili DR, Lal D, Reinthaler Rotterdam, The Netherlands, 13 Laboratory of Neurogenetics and Neuroscience, Institute G. -
Whole Genome Sequencing Puts Forward Hypotheses on Metastasis Evolution and Therapy in Colorectal Cancer
ARTICLE DOI: 10.1038/s41467-018-07041-z OPEN Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer Naveed Ishaque1,2,3, Mohammed L. Abba4,5, Christine Hauser4,5, Nitin Patil4,5, Nagarajan Paramasivam3,6, Daniel Huebschmann 3, Jörg Hendrik Leupold4,5, Gnana Prakash Balasubramanian2, Kortine Kleinheinz 3, Umut H. Toprak3, Barbara Hutter 2, Axel Benner7, Anna Shavinskaya4, Chan Zhou4,5, Zuguang Gu1,3, Jules Kerssemakers 3, Alexander Marx8, Marcin Moniuszko9, Miroslaw Kozlowski9, Joanna Reszec9, Jacek Niklinski9, Jürgen Eils3, Matthias Schlesner 3,10, Roland Eils 1,3,11, Benedikt Brors 2,12 & 1234567890():,; Heike Allgayer 4,5 Incomplete understanding of the metastatic process hinders personalized therapy. Here we report the most comprehensive whole-genome study of colorectal metastases vs. matched primary tumors. 65% of somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. Tumor- and metastasis-specific mutations harbor elevated levels of BRCAness. We confirm multistage progression with new components ARHGEF7/ARHGEF33. Recurrently mutated non-coding elements include ncRNAs RP11-594N15.3, AC010091, SNHG14,3’ UTRs of FOXP2, DACH2, TRPM3, XKR4, ANO5, CBL, CBLB, the latter four potentially dual protagonists in metastasis and efferocytosis-/PD-L1 mediated immunosuppression. Actionable metastasis- specific lesions include FAT1, FGF1, BRCA2, KDR, and AKT2-, AKT3-, and PDGFRA-3’ UTRs. Metastasis specific mutations are enriched in PI3K-Akt signaling, cell adhesion, ECM and hepatic stellate activation genes, suggesting genetic programs for site-specific colonization. Our results put forward hypotheses on tumor and metastasis evolution, and evidence for metastasis-specific events relevant for personalized therapy. -
Perkinelmer Genomics to Request the Saliva Swab Collection Kit for Patients That Cannot Provide a Blood Sample As Whole Blood Is the Preferred Sample
Autism and Intellectual Disability TRIO Panel Test Code TR002 Test Summary This test analyzes 2429 genes that have been associated with Autism and Intellectual Disability and/or disorders associated with Autism and Intellectual Disability with the analysis being performed as a TRIO Turn-Around-Time (TAT)* 3 - 5 weeks Acceptable Sample Types Whole Blood (EDTA) (Preferred sample type) DNA, Isolated Dried Blood Spots Saliva Acceptable Billing Types Self (patient) Payment Institutional Billing Commercial Insurance Indications for Testing Comprehensive test for patients with intellectual disability or global developmental delays (Moeschler et al 2014 PMID: 25157020). Comprehensive test for individuals with multiple congenital anomalies (Miller et al. 2010 PMID 20466091). Patients with autism/autism spectrum disorders (ASDs). Suspected autosomal recessive condition due to close familial relations Previously negative karyotyping and/or chromosomal microarray results. Test Description This panel analyzes 2429 genes that have been associated with Autism and ID and/or disorders associated with Autism and ID. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis is designed to detect the majority of deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines. Condition Description Autism Spectrum Disorder (ASD) refers to a group of developmental disabilities that are typically associated with challenges of varying severity in the areas of social interaction, communication, and repetitive/restricted behaviors. -
Protein Family Members. the GENE.FAMILY
Table 3: Protein family members. The GENE.FAMILY col- umn shows the gene family name defined either by HGNC (superscript `H', http://www.genenames.org/cgi-bin/family_ search) or curated manually by us from Entrez IDs in the NCBI database (superscript `C' for `Custom') that we have identified as corresonding for each ENTITY.ID. The members of each gene fam- ily that are in at least one of our synaptic proteome datasets are shown in IN.SYNAPSE, whereas those not found in any datasets are in the column OUT.SYNAPSE. In some cases the intersection of two HGNC gene families are needed to specify the membership of our protein family; this is indicated by concatenation of the names with an ampersand. ENTITY.ID GENE.FAMILY IN.SYNAPSE OUT.SYNAPSE AC Adenylate cyclasesH ADCY1, ADCY2, ADCY10, ADCY4, ADCY3, ADCY5, ADCY7 ADCY6, ADCY8, ADCY9 actin ActinsH ACTA1, ACTA2, ACTB, ACTC1, ACTG1, ACTG2 ACTN ActininsH ACTN1, ACTN2, ACTN3, ACTN4 AKAP A-kinase anchoring ACBD3, AKAP1, AKAP11, AKAP14, proteinsH AKAP10, AKAP12, AKAP17A, AKAP17BP, AKAP13, AKAP2, AKAP3, AKAP4, AKAP5, AKAP6, AKAP8, CBFA2T3, AKAP7, AKAP9, RAB32 ARFGEF2, CMYA5, EZR, MAP2, MYO7A, MYRIP, NBEA, NF2, SPHKAP, SYNM, WASF1 CaM Endogenous ligands & CALM1, CALM2, EF-hand domain CALM3 containingH CaMKK calcium/calmodulin- CAMKK1, CAMKK2 dependent protein kinase kinaseC CB CalbindinC CALB1, CALB2 CK1 Casein kinase 1C CSNK1A1, CSNK1D, CSNK1E, CSNK1G1, CSNK1G2, CSNK1G3 CRHR Corticotropin releasing CRHR1, CRHR2 hormone receptorsH DAGL Diacylglycerol lipaseC DAGLA, DAGLB DGK Diacylglycerol kinasesH DGKB, -
Alteraciones Sexo-Específicas En Sociabilidad Y Neuroinflamación En Un Modelo En Ratón De Autismo
Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales Alteraciones sexo-específicas en sociabilidad y neuroinflamación en un modelo en ratón de autismo Tesis presentada para optar por el título de Doctor de la Universidad de Buenos Aires en el área Ciencias Biológicas Nadia Kazlauskas Directora de tesis: Dra. Amaicha Mara Depino Consejera de estudios: Dra. Lidia Szczupak Lugar de trabajo: Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE-CONICET). Buenos Aires, 2017 1 Alteraciones sexo-específicas en sociabilidad y neuroinflamación en un modelo en ratón de autismo El autismo es un desorden del desarrollo neural caracterizado por impedimentos en la interacción social, habilidades comunicativas reducidas y la presencia de comportamientos estereotipados o repetitivos. Estos síntomas típicamente aparecen durante los primeros años de vida, y pueden afectar hasta a 1 en 38 niños, con una incidencia entre tres y cuatro veces mayor en varones que en mujeres. Actualmente no se conoce una única causa del desorden, sino que se proponen múltiples agentes etiológicos. Estudios postmortem realizados en humanos han establecido un nexo entre autismo y neuroinflamación. El objetivo general de esta tesis fue dilucidar el rol de la respuesta inflamatoria del sistema nervioso central, particularmente la activación glial, en el desarrollo del autismo. Para ello utilizamos el modelo de administración prenatal de Ácido Valproico (VPA) en ratón. Encontramos que la exposición al VPA produce una disminución en la sociabilidad de los ratones macho adultos, pero no así de los ratones hembra. Además, las hembras VPA presentan micro y astrogliosis en el cerebelo, y una respuesta inflamatoria periférica exacerbada ante la administración de un estímulo inflamatorio. -
Eco-HAB As a Fully Automated and Ecologically Relevant Assessment of Social Impairments in Mouse Models of Autism
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2016 Eco-HAB as a fully automated and ecologically relevant assessment of social impairments in mouse models of autism Puścian, Alicja ; Łęski, Szymon ; Kasprowicz, Grzegorz ; Winiarski, Maciej ; Borowska, Joanna ; Nikolaev, Tomasz ; Boguszewski, Paweł M ; Lipp, Hans-Peter ; Knapska, Ewelina Abstract: Eco-HAB is an open source, RFID-based system for automated measurement and analysis of social preference and in-cohort sociability in mice. The system closely follows murine ethology. It requires no contact between a human experimenter and tested animals, overcoming the confounding factors that lead to irreproducible assessment of murine social behavior between laboratories. In Eco-HAB, group- housed animals live in a spacious, four-compartment apparatus with shadowed areas and narrow tunnels, resembling natural burrows. Eco-HAB allows for assessment of the tendency of mice to voluntarily spend time together in ethologically relevant mouse group sizes. Custom-made software for automated tracking, data extraction, and analysis enables quick evaluation of social impairments. The developed protocols and standardized behavioral measures demonstrate high replicability. Unlike classic three-chambered sociability tests, Eco-HAB provides measurements of spontaneous, ecologically relevant social behaviors in group-housed animals. Results are obtained faster, with less manpower, and without confounding factors. DOI: https://doi.org/10.7554/eLife.19532 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-131758 Journal Article Published Version Originally published at: Puścian, Alicja; Łęski, Szymon; Kasprowicz, Grzegorz; Winiarski, Maciej; Borowska, Joanna; Nikolaev, Tomasz; Boguszewski, Paweł M; Lipp, Hans-Peter; Knapska, Ewelina (2016). -
Synaptic Pathways Related to Shank3 and Its Interaction Partner Prosapip1
International Graduate School in Molecular Medicine Ulm International PhD Programme in Molecular Medicine Synaptic pathways related to Shank3 and its interaction partner ProSAPiP1 Dissertation submitted in partial fulfilment of the requirements for the degree of „Doctor rerum naturalium” (Dr. rer. nat.) of the International Graduate School in Molecular Medicine Ulm Dominik Reim Born in Nürtingen, Germany Institute for Anatomy and Cell Biology, Head: Prof. Dr. Tobias M. Böckers 2016 1. Current dean / chairman of the Graduate School: Prof. Dr. Michael Kühl 2. Thesis Advisory Committee: - First supervisor: Prof. Dr. Tobias M. Böckers - Second supervisor: Prof. Dr. Thomas Wirth - Third supervisor: Dr. Chiara Verpelli 3. External reviewer: Prof. Dr. Matthias Kneussel 4. Day doctorate awarded: March 20, 2017 Results gained in my thesis have previously been published in the following publications: Reim, D., Distler, U., Halbedl, S., Verpelli, C., Sala, C., Bockmann, J., Tenzer, S., Boeckers, T.M., and Schmeisser, M.J. (2017). Proteomic analysis of postsynaptic density fractions from Shank3 mutant mice reveals brain region specific changes relevant to autism spectrum disorder. Front Mol Neurosci, doi: 10.3389/fnmol.2017.00026 Reim, D., Weis, T.M., Halbedl, S., Delling, J.P., Grabrucker, A.M., Boeckers, T.M., and Schmeisser, M.J. (2016). The Shank3 Interaction Partner ProSAPiP1 Regulates Postsynaptic SPAR Levels and the Maturation of Dendritic Spines in Hippocampal Neurons. Front Synaptic Neurosci 8, 13, doi: 10.3389/fnsyn.2016.00013 Vicidomini, C., Ponzoni, L., Lim, D., Schmeisser, M.J., Reim, D., Morello, N., Orellana, D., Tozzi, A., Durante, V., Scalmani, P., Mantegazza, M., Genazzani, A.A., Giustetto, M., Sala, M., Calabresi, P., Boeckers, T.M., Sala, C., and Verpelli, C. -
Using Gene Ontology to Describe the Role of the Neurexin-Neuroligin-SHANK Complex in Human, Mouse and Rat and Its Relevance to Autism Patel Et Al
Using Gene Ontology to describe the role of the neurexin-neuroligin-SHANK complex in human, mouse and rat and its relevance to autism Patel et al. Patel et al. BMC Bioinformatics (2015) 16:186 DOI 10.1186/s12859-015-0622-0 Patel et al. BMC Bioinformatics (2015) 16:186 DOI 10.1186/s12859-015-0622-0 METHODOLOGY ARTICLE Open Access Using Gene Ontology to describe the role of the neurexin-neuroligin-SHANK complex in human, mouse and rat and its relevance to autism Sejal Patel1,2,3, Paola Roncaglia4,5 and Ruth C. Lovering3* Abstract Background: People with an autistic spectrum disorder (ASD) display a variety of characteristic behavioral traits, including impaired social interaction, communication difficulties and repetitive behavior. This complex neurodevelopment disorder is known to be associated with a combination of genetic and environmental factors. Neurexins and neuroligins play a key role in synaptogenesis and neurexin-neuroligin adhesion is one of several processes that have been implicated in autism spectrum disorders. Results: In this report we describe the manual annotation of a selection of gene products known to be associated with autism and/or the neurexin-neuroligin-SHANK complex and demonstrate how a focused annotation approach leads to the creation of more descriptive Gene Ontology (GO) terms, as well as an increase in both the number of gene product annotations and their granularity, thus improving the data available in the GO database. Conclusions: The manual annotations we describe will impact on the functional analysis of a variety of future autism-relevant datasets. Comprehensive gene annotation is an essential aspect of genomic and proteomic studies, as the quality of gene annotations incorporated into statistical analysis tools affects the effective interpretation of data obtained throughgenomewideassociationstudies, next generation sequencing, proteomic and transcriptomic datasets.