DOCSLIB.ORG

Genetic Studies of Autism Spectrum Disorder in Asians

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genetic Studies of Autism Spectrum Disorder in Asians Overview Taiwanese Journal of Psychiatry (Taipei) Vol. 29 No. 3 2015 • 139 • Genetic Studies of Autism Spectrum Disorder in Asians Luke Y. Tsai, M.D.* The genetics of autism spectrum disorder (ASD) has been studied for more than three decades. Earlier twin and family studies have provided some support for a genetic rȏle in the development of ASD. More recent molecular techniques have identifi ed more than 400 potential genes involved in etiology of ASD. But many of the genes have also been identifi ed as potential genes for other neuropsychiatric disorders. The fi eld of ASD genetics has concluded that ASD as defi ned for the last three decades is a heterogeneous clinical disorder with heterogeneous genetic eti- ologies. This overview is to focus on the ethnic differences as a potential factor of the heterogeneous etiologies. In this overview, the author attempts to compile all available published ASD genetic studies in Asian populations to explore the direc- tions for future comparisons between Asian and Western ASD genetic studies. It is concluded that the quantity of the Asian ASD genetic studies is still quite limited, though there are a few studies indeed have found some ethnic differences in certain candidate genes for ASD. Key words: candidate gene, genome wide, copy number variation, ethnic difference (Taiwanese Journal of Psychiatry [Taipei] 2015; 29: 139-54) infantile autism in almost 400 siblings of autistic Introduction individuals in the literature. However, the 7 (1.8%) undocumented cases of autism among sib- When Kanner (1943) fi rst described infantile lings, did suggest a familial clustering of autism. autism, he suggested that it was resulted from an There were only 18 pairs of twins reported in the inborn defect of presumably constitutional origin literature before 1976. Hanson and Gottesman [1]. Over the next three decades, the possible rȏle (1976) concluded that the data were inadequate of genetic factors tended to be dismissed. In an for genetic analysis and there was no report on extensive review and analysis of the literature, offspring of autistic individuals. They concluded Hanson and Gottesman (1976) concluded that that the cause of infantile autism is unlikely to be there was no clear evidence exsits to indicate that genetic [2]. This conclusion is also supported by genetic factors play a rôle in infantile autism [2]. the lacking of identifi ed chromosome anomalies They found no adequately documented cases of associated with infantile autism [3] and by the lit- Departments of Psychiatry and Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, U.S.A. Received: October 2, 2015; accepted: October 7, 2015 *Corresponding author. No. 2385, Placid Way, Ann Arbor, 48105, Michigan, U.S.A. E-mail: Luke Y. Tsai <[email protected]> • 140 • Autism Spectrum Disorder erature review carried out by Smalley et al. (1988), showing only some 2% of cases with two autistic Search Strategy and children in the same family [4]. Identifi cation of Since then and over the last three decades, Relevant Studies considerable evidence has accumulated to support the thought that genetic factors may play a con- To identify the studies that support the ge- tributory hereditary rȏle in the devel-opment of netic role of the development of ASD, I conducted ASD in a subgroup of individuals with such a dis- a systematic literature search to locate the pub- order. Furthermore, the development of new tech- lished studies up to August 2015 that examined nologies in both molecular genetics and cytoge- the genetics of ASD in Chinese, Japanese and netics has substantially enhanced our capacity to Korean populations. The scope of the search was investigate the rôle of genetics in ASD. Attention limited to English-language journal articles. has turned to a more detailed consideration of spe- Publications were identifi ed by conducting cifi c aspects of genetic factors relating to the de- searches in the major scientifi c literature databas- velopment of ASD. es Pub-Med, MEDLINE, and PsycINFO. Search In this overview, I will focus on the genetic was also conducted by entering the following studies of ASD in Asian populations including terms: autism, autistic disorder, Asperger’s disor- ethnic Chinese, Japanese, and Koreans because der, PDD-NOS, pervasive developmental disor- some genetic studies have found “clear ethnic dif- der, autism spectrum disorder, gene, and genetics. ferences” in certain ASD related gene [e.g., gam- Key fi ndings and the bibliographies of many pre- ma-aminobutyric acid-A receptor subunit β3 vious reviews of genetics of ASD were incorpo- (GABRB3) gene [5], or confl icting results in dif- rated into the selection of studies. Reference lists ferent ethnic background [e.g., neuroligin 3 from relevant articles in recent editions of key (NLGN3) and neuroligin 4X (NLGN4X) genes [6]; journals likely to publish such genetic studies CD38 gene [7]. I hope that such a review would (e.g., Journal of Child Psychology and Psychiatry, build a database for future ASD genetic studies of Autism, Journal of Autism and Developmental comparisons between various ethnic groups to Disorders, Research of Autism Spectrum Disorder) help clarify the relevance of the genes to ASD. were also used to identify the relevant studies. Due to the limited space allowed for this overview paper, only the summaries of the identi- Twin Studies fi ed relevant studies are presented here. Readers of the Taiwanese Journal of Psychiatry are re- ‧ Ishijima and Kurita (2007) reported a pair of ferred to other related references for the details of Japanes MZ male twins concordant for DSM- the functions of the genes which are presented in IV Asperger’s disorder [8]. this paper. Family Studies ‧ To investigate the behavioral problems and par- enting style among children with autism and their siblings in an ethnic Chinese population, Tsai LY • 141 • Gau et al. (2010) recruited a total of 151 chil- dren with DSM-IV autistic disorder, aged 3-12 Cytogenetics and years, 134 siblings without autism, and 113 Chromosome Abnormalities normally developing controls. The investiga- tors found that children with autism had signifi - Cytogenetics mainly investigates chromo- cantly more severe behavioral problems, and some abnormalities, such as translocation, inver- obtained less affection and more overprotection sion, deletion, and duplication. Studies of the loca- and authoritarian controlling from their parents tion of chromosomal abnormalities and breakpoints than the unaffected siblings. But compared to can be extremely useful in the identifi cation and the controls, unaffected siblings have shown mapping of genes predisposing to any monogenic some behavioral problems. The investigators or polygenic disease. To date, there have been suggested that the unaffected siblings may be at many reports in the literature of chromosome ab- risk for developing the wide range of behav- normalities in autism covering a broad spectrum of ioral problems and impaired parent–child inter- anomalies, including terminal and interstitial dele- actions as exhibited by their siblings with au- tions, balanced and unbalanced translocations and tism [9]. inversions. The following is the study summaries, reporting chromosomal abnormalities in Asian in- Studies of Personality Traits dividuals with ASD or autistic behaviors: and Behavioral Characteristics Chromosome 2 - Deletion: a patient with au- tistic behavior, at 2p15-16.1 [11]; a 3 years and 4 ‧ Shen et al. (2011) reported the clinical and ge- months old girl with autistic features, at 2q24.2- nomic characteristics of three 16p11.2 deletion q24.3 [12]. carriers in a Chinese family. The father carries Chromosome 4 - Deletion: an 8 years old boy a de novo 16p11.2 deletion, and it was transmit- with ASD at 4q35.1-35.2 [13]. ted to the proband and sib. The proband pre- Chromosome 8 - Deletion: a 12-year-old boy sented with ASD, intellectual disability, learn- with ASD at 8p23.2-pter [13]. ing diffi culty, congenital malformations such as Chromosome 9 - Mosaic tetrasomy 9p: A atrial septal defect and scoliosis. His dysmor- 20-year-old female patient with autism [14]. phic features include myopia and strabismus, Chromosome 18 - Duplication: A 7-year-old fl at and broad nasal bridge, etc. While the fa- girl with autism, at 18q12.1 [15]. ther shared same neurodevelopmental prob- Chromosome X - Deletion: 2 brothers with lems as the proband, the younger brother does autistic behavior, at Xp11.22 [16]; Duplication: a not show many of the proband’s phenotypes. female with ASD, in Xp11.22-p11.23 [17]; Fragile The authors comment that their study demon- X: 8 children with ASD [18]. strates the different developmental trajectory Sex chromosomeaneuploidy – 2 ASD cases and discordant phenotypes among family mem- with 47, XXY, one ASD case with 47, XYY [19]. bers with the same 16p11.2 deletion and further Reciprocal chromosomal translocation be- illustrates the phenotypic complexity and het- tween long arms of chromosomes 4 and 14, desig- erogeneity of the 16p11.2 deletion [10]. nated t(4;14)(q31.3;q24.1) - in a patient with Asperger’s disorder [19]. • 142 • Autism Spectrum Disorder chromosomal abnormality; and has been located Candidate Genes positionally by linkage studies [22]. Over the last two decades, many candidate The fi rst molecular genetic studies of autism gene studies have been conducted, and more than took form in candidate gene association studies. 100 functional or positional candidate genes have The introduction of cost-effective resequencing been tested directly. The majority of them did not has made it possible to build on cytogenetic stud- reveal a conclusive evidence of involvement in ies and obtain evidence for the involvement of ASD by showing clear picture of either positive specifi c candidate genes in the ASDs. Candidate association at a certain gene or genomic locus or gene study is hypothesis-driven research which identifi cation of disease-relevant variations or choses several candidate genes for additional mutations.
Load more

Recommended publications
  • A Guide to Glutamate Receptors
    A guide to glutamate receptors 1 Contents Glutamate receptors . 4 Ionotropic glutamate receptors . 4 - Structure ........................................................................................................... 4 - Function ............................................................................................................ 5 - AMPA receptors ................................................................................................. 6 - NMDA receptors ................................................................................................. 6 - Kainate receptors ............................................................................................... 6 Metabotropic glutamate receptors . 8 - Structure ........................................................................................................... 8 - Function ............................................................................................................ 9 - Group I: mGlu1 and mGlu5. .9 - Group II: mGlu2 and mGlu3 ................................................................................. 10 - Group III: mGlu4, mGlu6, mGlu7 and mGlu8 ............................................................ 10 Protocols and webinars . 11 - Protocols ......................................................................................................... 11 - Webinars ......................................................................................................... 12 References and further reading . 13 Excitatory synapse pathway
    [Show full text]
  • Chromosome 18
    Chromosome 18 Description Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 18, one copy inherited from each parent, form one of the pairs. Chromosome 18 spans about 78 million DNA building blocks (base pairs) and represents approximately 2.5 percent of the total DNA in cells. Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 18 likely contains 200 to 300 genes that provide instructions for making proteins. These proteins perform a variety of different roles in the body. Health Conditions Related to Chromosomal Changes The following chromosomal conditions are associated with changes in the structure or number of copies of chromosome 18. Distal 18q deletion syndrome Distal 18q deletion syndrome occurs when a piece of the long (q) arm of chromosome 18 is missing. The term "distal" means that the missing piece (deletion) occurs near one end of the chromosome arm. The signs and symptoms of distal 18q deletion syndrome include delayed development and learning disabilities, short stature, weak muscle tone ( hypotonia), foot abnormalities, and a wide variety of other features. The deletion that causes distal 18q deletion syndrome can occur anywhere between a region called 18q21 and the end of the chromosome. The size of the deletion varies among affected individuals. The signs and symptoms of distal 18q deletion syndrome are thought to be related to the loss of multiple genes from this part of the long arm of chromosome 18.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Kainate Receptors in Health and Disease
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuron Review Kainate Receptors in Health and Disease Juan Lerma1,* and Joana M. Marques1 1Instituto de Neurociencias, CSIC-UMH, San Juan de Alicante, 03550 Spain *Correspondence: [email protected] http://dx.doi.org/10.1016/j.neuron.2013.09.045 Our understanding of the molecular properties of kainate receptors and their involvement in synaptic phys- iology has progressed significantly over the last 30 years. A plethora of studies indicate that kainate receptors are important mediators of the pre- and postsynaptic actions of glutamate, although the mechanisms under- lying such effects are still often a topic for discussion. Three clear fields related to their behavior have emerged: there are a number of interacting proteins that pace the properties of kainate receptors; their activity is unconventional since they can also signal through G proteins, behaving like metabotropic recep- tors; they seem to be linked to some devastating brain diseases. Despite the significant progress in their importance in brain function, kainate receptors remain somewhat puzzling. Here we examine discoveries linking these receptors to physiology and their probable implications in disease, in particular mood disorders, and propose some ideas to obtain a deeper understanding of these intriguing proteins. A Historical Overview The absence of specific antibodies against different KAR Most excitatory synapses in the brain use the amino acid gluta- subunits has been a significant limitation in terms of exploring re- mate as a neurotransmitter. Since the excitatory properties of ceptor distribution. Thus, most of the information regarding their glutamate were postulated nearly 40 years ago, an extraordinary tissue expression comes from in situ hybridization studies that, wealth of data has accumulated on the types of synaptic re- although informative, cannot reveal the subcellular distribution sponses triggered by this neurotransmitter.
    [Show full text]
  • First Case Report of Maternal Mosaic Tetrasomy 9P Incidentally Detected on Non-Invasive Prenatal Testing
    G C A T T A C G G C A T genes Article First Case Report of Maternal Mosaic Tetrasomy 9p Incidentally Detected on Non-Invasive Prenatal Testing Wendy Shu 1,*, Shirley S. W. Cheng 2 , Shuwen Xue 3, Lin Wai Chan 1, Sung Inda Soong 4, Anita Sik Yau Kan 5 , Sunny Wai Hung Cheung 6 and Kwong Wai Choy 3,* 1 Department of Obstetrics and Gynaecology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China; [email protected] 2 Clinical Genetic Service, Hong Hong Children Hospital, Ngau Tau Kok, Hong Kong, China; [email protected] 3 Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, Hong Kong, China; [email protected] 4 Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China; [email protected] 5 Prenatal Diagnostic Laboratory, Tsan Yuk Hospital, Sai Ying Pun, Hong Kong, China; [email protected] 6 NIPT Department, NGS Lab, Xcelom Limited, Hong Kong, China; [email protected] * Correspondence: [email protected] (W.S.); [email protected] (K.W.C.); Tel.: +852-25-957-359 (W.S.); +852-35-053-099 (K.W.C.) Abstract: Tetrasomy 9p (ORPHA:3390) is a rare syndrome, hallmarked by growth retardation; psychomotor delay; mild to moderate intellectual disability; and a spectrum of skeletal, cardiac, renal and urogenital defects. Here we present a Chinese female with good past health who conceived her pregnancy naturally. Non-invasive prenatal testing (NIPT) showed multiple chromosomal aberrations were consistently detected in two sampling times, which included elevation in DNA from Citation: Shu, W.; Cheng, S.S.W.; chromosome 9p.
    [Show full text]
  • Supplemental Materials ZNF281 Enhances Cardiac Reprogramming
    Supplemental Materials ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E. Dickson, Kunhua Song, Wenduo Ye, Min S. Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A. Posner, Rhonda Bassel-Duby and Eric N. Olson Supplemental Table 1; related to Figure 1. Supplemental Table 2; related to Figure 1. Supplemental Table 3; related to the “quantitative mRNA measurement” in Materials and Methods section. Supplemental Table 4; related to the “ChIP-seq, gene ontology and pathway analysis” and “RNA-seq” and gene ontology analysis” in Materials and Methods section. Supplemental Figure S1; related to Figure 1. Supplemental Figure S2; related to Figure 2. Supplemental Figure S3; related to Figure 3. Supplemental Figure S4; related to Figure 4. Supplemental Figure S5; related to Figure 6. Supplemental Table S1. Genes included in human retroviral ORF cDNA library. Gene Gene Gene Gene Gene Gene Gene Gene Symbol Symbol Symbol Symbol Symbol Symbol Symbol Symbol AATF BMP8A CEBPE CTNNB1 ESR2 GDF3 HOXA5 IL17D ADIPOQ BRPF1 CEBPG CUX1 ESRRA GDF6 HOXA6 IL17F ADNP BRPF3 CERS1 CX3CL1 ETS1 GIN1 HOXA7 IL18 AEBP1 BUD31 CERS2 CXCL10 ETS2 GLIS3 HOXB1 IL19 AFF4 C17ORF77 CERS4 CXCL11 ETV3 GMEB1 HOXB13 IL1A AHR C1QTNF4 CFL2 CXCL12 ETV7 GPBP1 HOXB5 IL1B AIMP1 C21ORF66 CHIA CXCL13 FAM3B GPER HOXB6 IL1F3 ALS2CR8 CBFA2T2 CIR1 CXCL14 FAM3D GPI HOXB7 IL1F5 ALX1 CBFA2T3 CITED1 CXCL16 FASLG GREM1 HOXB9 IL1F6 ARGFX CBFB CITED2 CXCL3 FBLN1 GREM2 HOXC4 IL1F7
    [Show full text]
  • Coupling of Autism Genes to Tissue-Wide Expression and Dysfunction of Synapse, Calcium Signalling and Transcriptional Regulation
    PLOS ONE RESEARCH ARTICLE Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation 1 2,3 4 1,5 Jamie ReillyID *, Louise Gallagher , Geraldine Leader , Sanbing Shen * 1 Regenerative Medicine Institute, School of Medicine, Biomedical Science Building, National University of a1111111111 Ireland (NUI) Galway, Galway, Ireland, 2 Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland, 3 Trinity Translational Medicine Institute, Trinity Centre for Health SciencesÐTrinity College a1111111111 Dublin, St. James's Hospital, Dublin, Ireland, 4 Irish Centre for Autism and Neurodevelopmental Research a1111111111 (ICAN), Department of Psychology, National University of Ireland (NUI) Galway, Galway, Ireland, a1111111111 5 FutureNeuro Research Centre, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland a1111111111 * [email protected] (JR); [email protected] (SS) Abstract OPEN ACCESS Citation: Reilly J, Gallagher L, Leader G, Shen S Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied (2020) Coupling of autism genes to tissue-wide with many co-morbidities. Recent genetic studies have identified various pathways from expression and dysfunction of synapse, calcium hundreds of candidate risk genes with varying levels of association to ASD. However, it is signalling and transcriptional regulation. PLoS ONE unknown which pathways are specific to the core symptoms or which are shared by the co- 15(12): e0242773. https://doi.org/10.1371/journal. pone.0242773 morbidities. We hypothesised that critical ASD candidates should appear widely across dif- ferent scoring systems, and that comorbidity pathways should be constituted by genes Editor: Nirakar Sahoo, The University of Texas Rio Grande Valley, UNITED STATES expressed in the relevant tissues.
    [Show full text]
  • Mechanisms Underlying the EEG Biomarker in Dup15q Syndrome Joel Frohlich1,2,3* , Lawrence T
    Frohlich et al. Molecular Autism (2019) 10:29 https://doi.org/10.1186/s13229-019-0280-6 RESEARCH Open Access Mechanisms underlying the EEG biomarker in Dup15q syndrome Joel Frohlich1,2,3* , Lawrence T. Reiter4, Vidya Saravanapandian2, Charlotte DiStefano2, Scott Huberty2,5, Carly Hyde2, Stormy Chamberlain6, Carrie E. Bearden7, Peyman Golshani8, Andrei Irimia9, Richard W. Olsen10, Joerg F. Hipp1† and Shafali S. Jeste2† Abstract Background: Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods: To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results: Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz).
    [Show full text]
  • Mosaic Tetrasomy 9P at Amniocentesis: Prenatal Diagnosis, Molecular Cytogenetic Characterization, and Literature Review
    Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 79e85 Contents lists available at ScienceDirect Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com Short Communication Mosaic tetrasomy 9p at amniocentesis: Prenatal diagnosis, molecular cytogenetic characterization, and literature review Chih-Ping Chen a,b,c,d,e,f,*, Liang-Kai Wang a, Schu-Rern Chern b, Peih-Shan Wu g, Yu-Ting Chen b, Yu-Ling Kuo h, Wen-Lin Chen a, Meng-Shan Lee a, Wayseen Wang b,i a Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan b Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan c Department of Biotechnology, Asia University, Taichung, Taiwan d School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan e Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan f Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan g Gene Biodesign Co. Ltd, Taipei, Taiwan h Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan i Department of Bioengineering, Tatung University, Taipei, Taiwan article info abstract Article history: Objective: This study was aimed at prenatal diagnosis of mosaic tetrasomy 9p and reviewing the Accepted 17 December 2013 literature. Materials and methods: A 37-year-old woman underwent amniocentesis at 20 weeks’ gestation because Keywords: of advanced maternal age and fetal ascites. Cytogenetic analysis of cultured amniocytes revealed 21.4% amniocentesis (6/28 colonies) mosaicism for a supernumerary i(9p). Repeat amniocentesis was performed at 23 weeks’ mosaicism gestation. Array comparative genomic hybridization, interphase fluorescence in situ hybridization, and supernumerary isochromosome 9p quantitative fluorescent polymerase chain reaction were applied to uncultured amniocytes, and con- tetrasomy 9p ventional cytogenetic analysis was applied to cultured amniocytes.
    [Show full text]
  • Aneuploidy and Aneusomy of Chromosome 7 Detected by Fluorescence in Situ Hybridization Are Markers of Poor Prognosis in Prostate Cancer'
    [CANCERRESEARCH54,3998-4002,August1, 19941 Advances in Brief Aneuploidy and Aneusomy of Chromosome 7 Detected by Fluorescence in Situ Hybridization Are Markers of Poor Prognosis in Prostate Cancer' Antonio Alcaraz, Satoru Takahashi, James A. Brown, John F. Herath, Erik J- Bergstralh, Jeffrey J. Larson-Keller, Michael M Lieber, and Robert B. Jenkins2 Depart,nent of Urology [A. A., S. T., J. A. B., M. M. U, Laboratory Medicine and Pathology (J. F. H., R. B. fl, and Section of Biostatistics (E. J. B., J. J. L-JCJ, Mayo Clinic and Foundation@ Rochester, Minnesota 55905 Abstract studies on prostate carcinoma samples. Interphase cytogenetic analy sis using FISH to enumerate chromosomes has the potential to over Fluorescence in situ hybridization is a new methodologj@which can be come many of the difficulties associated with traditional cytogenetic used to detect cytogenetic anomalies within interphase tumor cells. We studies. Previous studies from this institution have demonstrated that used this technique to identify nonrandom numeric chromosomal alter ations in tumor specimens from the poorest prognosis patients with path FISH analysis with chromosome enumeration probes is more sensitive ological stages T2N@M,Jand T3NOMOprostate carcinomas. Among 1368 than FCM for detecting aneuploid prostate cancers (4, 5, 7). patients treated by radical prostatectomy, 25 study patients were ascer We designed a case-control study to test the hypothesis that spe tamed who died most quickly from progressive prostate carcinoma within cific, nonrandom cytogenetic changes are present in tumors removed 3 years of diagnosis and surgery. Tumors from 25 control patients who from patients with prostate carcinomas with poorest prognoses .
    [Show full text]
  • Sex Differences in Glutamate Receptor Gene Expression in Major Depression and Suicide
    Molecular Psychiatry (2015) 20, 1057–1068 © 2015 Macmillan Publishers Limited All rights reserved 1359-4184/15 www.nature.com/mp IMMEDIATE COMMUNICATION Sex differences in glutamate receptor gene expression in major depression and suicide AL Gray1, TM Hyde2,3, A Deep-Soboslay2, JE Kleinman2 and MS Sodhi1,4 Accumulating data indicate that the glutamate system is disrupted in major depressive disorder (MDD), and recent clinical research suggests that ketamine, an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor (GluR), has rapid antidepressant efficacy. Here we report findings from gene expression studies of a large cohort of postmortem subjects, including subjects with MDD and controls. Our data reveal higher expression levels of the majority of glutamatergic genes tested in the dorsolateral prefrontal cortex (DLPFC) in MDD (F21,59 = 2.32, P = 0.006). Posthoc data indicate that these gene expression differences occurred mostly in the female subjects. Higher expression levels of GRIN1, GRIN2A-D, GRIA2-4, GRIK1-2, GRM1, GRM4, GRM5 and GRM7 were detected in the female patients with MDD. In contrast, GRM5 expression was lower in male MDD patients relative to male controls. When MDD suicides were compared with MDD non-suicides, GRIN2B, GRIK3 and GRM2 were expressed at higher levels in the suicides. Higher expression levels were detected for several additional genes, but these were not statistically significant after correction for multiple comparisons. In summary, our analyses indicate a generalized disruption of the regulation of the GluRs in the DLPFC of females with MDD, with more specific GluR alterations in the suicides and in the male groups.
    [Show full text]
  • Chapter Chapter 2
    Chapter Chapter 2 Attenuated AMPA receptor expression allows glioblastoma cell survival in glutamate-rich environment Dannis G. van Vuurden, Maryam Yazdani, Ingeborg Bosma, Richard A.J.F. Broekhuizen, Tjeerd J. Postma, Jan J. Heimans, Paul van der Valk, Eleonora Aronica, Bakhos A. Tannous, Thomas Würdinger, Gertjan J. L. Kaspers, Jacqueline Cloos PLoS ONE 2009; 4(6): e5953 23 Proefschrift1.indd 23 24-04-14 13:54 ABSTRACT Background: Glioblastoma multiforme (GBM) cells secrete large amounts of glutamate that can trigger AMPA-type glutamate receptors (AMPARs). This commonly results in Na+ and Ca2+-permeability and thereby in excitotoxic cell death of the surrounding neurons. Here we investigated how the GBM cells themselves survive in a glutamate-rich environment. Methods and Findings: In silico analysis of published reports shows down-regulation of all ionotropic glutamate receptors in GBM as compared to normal brain. In vitro, in all GBM samples tested, mRNA expression of AMPAR subunit GluR1, 2 and 4 was relatively low compared to adult and fetal total brain mRNA and adult cerebellum mRNA. These findings were in line with primary GBM samples, in which protein expression patterns were down- regulated as compared to the normal tissue. Furthermore, mislocalized expression of these receptors was found. Sequence analysis of GluR2 RNA in primary and established GBM cell lines showed that the GluR2 subunit was found to be partly unedited. Conclusions: Together with the lack of functional effect of AMPAR inhibition by NBQX our results suggest that down-regulation and non-functionality of AMPARs, enable GBM cells to survive in a high glutamate environment without going into excitotoxic cell death themselves.
    [Show full text]