Breakthroughs in the Search for Dyslexia Candidate Genes
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Rare Variants in Dynein Heavy Chain Genes in Two Individuals with Situs
bioRxiv preprint doi: https://doi.org/10.1101/2020.03.30.011783; this version posted March 31, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia Andrea Bieder1,*, Elisabet Einarsdottir1,2,3, Hans Matsson4,5,6, Harriet E. Nilsson1,7, Jesper Eisfeldt5,8,9, Anca Dragomir10, Martin Paucar11, Tobias Granberg11,12, Tie-Qiang Li13, Anna Lindstrand5,8,14, Juha Kere1,2,15, Isabel Tapia-Páez16,* 1Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden 2Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland and Folkhälsan Institute of Genetics, Helsinki, Finland 3Science for Life Laboratory, Department of Gene Technology, KTH-Royal Institute of Technology, Solna, Sweden 4Department of Women´s and Children´s Health, Karolinska Institutet, Solna, Sweden 5Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden 6Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden 7Department of Biomedical Engineering and Health Systems, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Huddinge, Sweden 8Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden 9Science for Life Laboratory, -
(12) Patent Application Publication (10) Pub. No.: US 2005/0010974A1 Milligan Et Al
US 20050010974A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0010974A1 Milligan et al. (43) Pub. Date: Jan. 13, 2005 (54) PROMOTERS FOR REGULATION OF GENE Publication Classification EXPRESSION IN PLANT ROOTS (51) Int. Cl." ............................ C12N 15/82; C12O 1/68; (76) Inventors: Stephen B Milligan, Kirkland, WA C12N 15/87; C12N 15/63; (US); Dale Skalla, Research Triangle C12N 15/85; C12N 5/10; Park, NC (US); Kay Lawton, Research C12N 15/09; CO7H 21/04 Triangle Park, NC (US) (52) U.S. Cl. ..................... 800/287; 536/23.6; 435/320.1; 435/455; 435/419; 435/468; Correspondence Address: 800/278; 435/6; 536/24.33 Randee S Schwatz Syngenta Biotechnology 3054 Cornwallis Road (57) ABSTRACT Research Triangle Park, NC 27709 (US) The present invention is directed to promoters isolated from (21) Appl. No.: 10/490,147 maize and functional equivalents thereto. The promoters of the present invention have particular utility in driving root (22) PCT Filed: Nov. 4, 2002 Specific expression of heterologous genes that impart (86) PCT No.: PCT/US02/35374 increased agronomic, horticultural and/or pesticidal charac teristics to a given promoters of the invention and trans (30) Foreign Application Priority Data formed plant tissues containing DNA molecules comprising a promoter of the invention operably linked to a heterolo Nov. 7, 2001 (US)........................................... 60337026 gous gene or genes, and Seeds thereof. US 2005/0010974 A1 Jan. 13, 2005 PROMOTERS FOR REGULATION OF GENE latory Sequences may be short regions of DNA sequence EXPRESSION IN PLANT ROOTS 6-100 base pairs that define the binding sites for trans-acting factors, Such as transcription factors. -
Downloaded and Searched Against the Dbest Database to Identify Ests
BMC Genomics BioMed Central Research article Open Access A transcription map of the 6p22.3 reading disability locus identifying candidate genes Eric R Londin1, Haiying Meng2 and Jeffrey R Gruen*2 Address: 1Graduate Program in Genetics, State University of New York at Stony Brook, NY, USA and 2Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA Email: Eric R Londin - [email protected]; Haiying Meng - [email protected]; Jeffrey R Gruen* - [email protected] * Corresponding author Published: 30 June 2003 Received: 22 April 2003 Accepted: 30 June 2003 BMC Genomics 2003, 4:25 This article is available from: http://www.biomedcentral.com/1471-2164/4/25 © 2003 Londin et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. reading disabilitydyslexia6p22.3In silicoESTs Abstract Background: Reading disability (RD) is a common syndrome with a large genetic component. Chromosome 6 has been identified in several linkage studies as playing a significant role. A more recent study identified a peak of transmission disequilibrium to marker JA04 (G72384) on chromosome 6p22.3, suggesting that a gene is located near this marker. Results: In silico cloning was used to identify possible candidate genes located near the JA04 marker. The 2 million base pairs of sequence surrounding JA04 was downloaded and searched against the dbEST database to identify ESTs. In total, 623 ESTs from 80 different tissues were identified and assembled into 153 putative coding regions from 19 genes and 2 pseudogenes encoded near JA04. -
Speech Sound Disorder Influenced by a Locus in 15Q14 Region
Behav Genet DOI 10.1007/s10519-006-9090-7 ORIGINAL PAPER Speech Sound Disorder Influenced by a Locus in 15q14 Region Catherine M. Stein Æ Christopher Millard Æ Amy Kluge Æ Lara E. Miscimarra Æ Kevin C. Cartier Æ Lisa A. Freebairn Æ Amy J. Hansen Æ Lawrence D. Shriberg Æ H. Gerry Taylor Æ Barbara A. Lewis Æ Sudha K. Iyengar Received: 27 September 2005 / Accepted: 23 May 2006 Ó Springer Science+Business Media, Inc. 2006 Abstract Despite a growing body of evidence in- phonological memory, and that linkage at D15S118 was dicating that speech sound disorder (SSD) has an un- potentially influenced by a parent-of-origin effect derlying genetic etiology, researchers have not yet (LOD score increase from 0.97 to 2.17, P = 0.0633). identified specific genes predisposing to this condition. These results suggest shared genetic determinants in The speech and language deficits associated with SSD this chromosomal region for SSD, autism, and PWS/AS. are shared with several other disorders, including dys- lexia, autism, Prader-Willi Syndrome (PWS), and An- Keywords Phonology Æ Speech Æ Language Æ gelman’s Syndrome (AS), raising the possibility of gene Parent-of-origin Æ Allele-sharing sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also Introduction shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD Speech–sound disorder (SSD) is a common communi- phenotypes and microsatellite markers on the chromo- cation disorder of unknown etiology with an estimated some 15q14–21 region, which has been associated with prevalence of 15.2% in children at age 3, persisting in autism, PWS/AS, and dyslexia. -
A Ciliopathy-Associated COPD Endotype
Perotin et al. Respir Res (2021) 22:74 https://doi.org/10.1186/s12931-021-01665-4 LETTER TO THE EDITOR Open Access CiliOPD: a ciliopathy-associated COPD endotype Jeanne‑Marie Perotin1,2, Myriam Polette1,3, Gaëtan Deslée1,2 and Valérian Dormoy1* Abstract The pathophysiology of chronic obstructive pulmonary disease (COPD) relies on airway remodelling and infam‑ mation. Alterations of mucociliary clearance are a major hallmark of COPD caused by structural and functional cilia abnormalities. Using transcriptomic databases of whole lung tissues and isolated small airway epithelial cells (SAEC), we comparatively analysed cilia‑associated and ciliopathy‑associated gene signatures from a set of 495 genes in 7 datasets including 538 non‑COPD and 508 COPD patients. This bio‑informatics approach unveils yet undescribed cilia and ciliopathy genes associated with COPD including NEK6 and PROM2 that may contribute to the pathology, and suggests a COPD endotype exhibiting ciliopathy features (CiliOPD). Keywords: COPD, Cilia, Transcriptomic Introduction signatures in 7 datasets including 538 non-COPD and Cilia dysfunction is a hallmark of chronic obstructive 508 COPD patients. infammatory lung diseases [1]. Alterations of both cilia structure and function alter airway mucociliary clear- Methods ance. Epithelial remodelling is indicted in COPD patho- Gene selection genesis, including distal to proximal repatterning of the Human cilia-associated genes (n = 447) and ciliopathy- small airways and altered generation of motile and pri- associated genes (n = -
Molecular Genetics of Dyslexia: an Overview
DYSLEXIA Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/dys.1464 ■ Molecular Genetics of Dyslexia: An Overview Amaia Carrion-Castillo1*, Barbara Franke2 and Simon E. Fisher1,2 1Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands 2Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Netherlands Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may con- tribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies have moved from mapping potential risk loci, through identification of associated gene variants, to characterization of gene function in cellular and animal model systems. Work thus far has highlighted some intriguing mechanistic pathways, such as neuronal migration, axon guidance, and ciliary biology, but it is clear that we still have much to learn about the molecular networks that are involved. We end the review by highlighting the past, present, and future contributions of the Dutch Dyslexia Programme to studies of genetic factors. In particular, we emphasize the importance of relating genetic information to intermediate neurobiological measures, as well as the value of incorporating longitudinal and developmental data into molecular designs. Copyright © 2013 John Wiley & Sons, Ltd. Keywords: molecular genetics; dyslexia; review INTRODUCTION Over the past decade or so, advances in molecular technologies have enabled researchers to begin pinpointing potential genetic risk factors implicated in human neurodevelopmental disorders (Graham & Fisher, 2013). A significant amount of work has focused on developmental dyslexia (specific reading disability). -
Supplementary Data
Supplementary Fig. 1 A B Responder_Xenograft_ Responder_Xenograft_ NON- NON- Lu7336, Vehicle vs Lu7466, Vehicle vs Responder_Xenograft_ Responder_Xenograft_ Sagopilone, Welch- Sagopilone, Welch- Lu7187, Vehicle vs Lu7406, Vehicle vs Test: 638 Test: 600 Sagopilone, Welch- Sagopilone, Welch- Test: 468 Test: 482 Responder_Xenograft_ NON- Lu7860, Vehicle vs Responder_Xenograft_ Sagopilone, Welch - Lu7558, Vehicle vs Test: 605 Sagopilone, Welch- Test: 333 Supplementary Fig. 2 Supplementary Fig. 3 Supplementary Figure S1. Venn diagrams comparing probe sets regulated by Sagopilone treatment (10mg/kg for 24h) between individual models (Welsh Test ellipse p-value<0.001 or 5-fold change). A Sagopilone responder models, B Sagopilone non-responder models. Supplementary Figure S2. Pathway analysis of genes regulated by Sagopilone treatment in responder xenograft models 24h after Sagopilone treatment by GeneGo Metacore; the most significant pathway map representing cell cycle/spindle assembly and chromosome separation is shown, genes upregulated by Sagopilone treatment are marked with red thermometers. Supplementary Figure S3. GeneGo Metacore pathway analysis of genes differentially expressed between Sagopilone Responder and Non-Responder models displaying –log(p-Values) of most significant pathway maps. Supplementary Tables Supplementary Table 1. Response and activity in 22 non-small-cell lung cancer (NSCLC) xenograft models after treatment with Sagopilone and other cytotoxic agents commonly used in the management of NSCLC Tumor Model Response type -
Mir-645 in Breast Cancer Was the Candidate Gene We Chose
European Review for Medical and Pharmacological Sciences 2017; 21: 4129-4136 Downregulation of microRNA-645 suppresses breast cancer cell metastasis via targeting DCDC2 Y. CAI, W.-F. LI, Y. SUN, K. LIU Department of Breast Surgery, Jilin Cancer Hospital, Changchun, Jilin Province, China Abstract. – OBJECTIVE: To analyze the func- large and medium cities, such as Beijing and tioning mode of miR-645 on breast cancer cell Shanghai3. The pathogenesis of BC is still unclear metastasis and provide therapeutic targets for so far, and it is thought that the occurrence and breast cancer. MATERIALS AND METHODS: development of BC are associated with a variety Quantitative of factors, such as genetic factors, endocrine Real-time PCR (qRT-PCR) assay was employed 4 to detect miR-645 expression level. Wound heal- factors and malignant benign breast lesions . Al- ing assay and transwell assay were performed though there are various treatment methods at to investigate metastasis capacity of breast can- present and the initial curative effects of tradi- cer cells. Protein levels were assessed by West- tional surgery, chemotherapy and other treatment ern blotting assay. The target gene was predict- measures are efficient, the treatment often fails ed and verified by bioinformatics analysis and due to the malignant biological behaviors of BC, luciferase assay. 5,6 RESULTS: MiR-645 was upregulated in breast such as easy relapse and early metastasis , so cancer tissues when compared with pericarci- it is particularly important to deeply focus on nous tissues (n=60). Downregulated miR-645 the formation mechanism of malignant biological could attenuate breast cancer cell migration and behaviors of BC.As a type of small non-coding invasion capacities, as well as inhibit the process ribose nucleic acid (RNA) transcripts, microRNA of epithelial-mesenchymal transition (EMT). -
Knockdown of Dyslexia-Gene Dcdc2 Interferes with Speech Sound Discrimination in Continuous Streams
The Journal of Neuroscience, April 27, 2016 • 36(17):4895–4906 • 4895 Neurobiology of Disease Knockdown of Dyslexia-Gene Dcdc2 Interferes with Speech Sound Discrimination in Continuous Streams X Tracy Michelle Centanni,1,2 Anne B. Booker,3 Fuyi Chen,3 XAndrew M. Sloan,1 Ryan S. Carraway,1 Robert L. Rennaker,1 Joseph J. LoTurco,3 and Michael P. Kilgard1 1University of Texas at Dallas, Richardson, Texas 75080, 2Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and 3University of Connecticut, Storrs, Connecticut 06269 Dyslexia is the most common developmental language disorder and is marked by deficits in reading and phonological awareness. One theory of dyslexia suggests that the phonological awareness deficit is due to abnormal auditory processing of speech sounds. Variants in DCDC2 and several other neural migration genes are associated with dyslexia and may contribute to auditory processing deficits. In the current study, we tested the hypothesis that RNAi suppression of Dcdc2 in rats causes abnormal cortical responses to sound and impaired speech sound discrimination. In the current study, rats were subjected in utero to RNA interference targeting of the gene Dcdc2 or a scrambledsequence.Primaryauditorycortex(A1)responseswereacquiredfrom11rats(5withDcdc2RNAi;DCϪ)beforeanybehavioral training.Aseparategroupof8rats(3DCϪ)weretrainedonavarietyofspeechsounddiscriminationtasks,andauditorycortexresponses were acquired following training. Dcdc2 RNAi nearly eliminated the ability of rats to identify specific speech sounds from a continuous train of speech sounds but did not impair performance during discrimination of isolated speech sounds. The neural responses to speech sounds in A1 were not degraded as a function of presentation rate before training. These results suggest that A1 is not directly involved in the impaired speech discrimination caused by Dcdc2 RNAi. -
Mclean, Chelsea.Pdf
COMPUTATIONAL PREDICTION AND EXPERIMENTAL VALIDATION OF NOVEL MOUSE IMPRINTED GENES A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Chelsea Marie McLean August 2009 © 2009 Chelsea Marie McLean COMPUTATIONAL PREDICTION AND EXPERIMENTAL VALIDATION OF NOVEL MOUSE IMPRINTED GENES Chelsea Marie McLean, Ph.D. Cornell University 2009 Epigenetic modifications, including DNA methylation and covalent modifications to histone tails, are major contributors to the regulation of gene expression. These changes are reversible, yet can be stably inherited, and may last for multiple generations without change to the underlying DNA sequence. Genomic imprinting results in expression from one of the two parental alleles and is one example of epigenetic control of gene expression. So far, 60 to 100 imprinted genes have been identified in the human and mouse genomes, respectively. Identification of additional imprinted genes has become increasingly important with the realization that imprinting defects are associated with complex disorders ranging from obesity to diabetes and behavioral disorders. Despite the importance imprinted genes play in human health, few studies have undertaken genome-wide searches for new imprinted genes. These have used empirical approaches, with some success. However, computational prediction of novel imprinted genes has recently come to the forefront. I have developed generalized linear models using data on a variety of sequence and epigenetic features within a training set of known imprinted genes. The resulting models were used to predict novel imprinted genes in the mouse genome. After imposing a stringency threshold, I compiled an initial candidate list of 155 genes. -
Evolutionary Diversification of DYX1C1 Transcripts Via an HERV-H LTR Integration Event
Genes Genet. Syst. (2011) 86, p. 277–284 Evolutionary diversification of DYX1C1 transcripts via an HERV-H LTR integration event Yun-Ji Kim1, Jae-Won Huh2, Dae-Soo Kim3, Kyudong Han4, Hwan-Mook Kim5 and Heui-Soo Kim1* 1Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea 2National Primate Research Center (NPRC), KRIBB, Ochang, Chungbuk 363-883, Republic of Korea 3Korean BioInformation Center, KRIBB, Daejeon 305-806, Republic of Korea 4Department of Nanobiomedical Science & WCU Research Center, Dankook University, Cheonan 330-714, Republic of Korea 5Department of Pharmacy, College of Pharmacy, Gachon University of Medicine and Science, Incheon 406-799, Republic of Korea (Received 21 May 2011, accepted 13 August 2011) DYX1C1 is a candidate gene for developmental dyslexia and has three alterna- tive pre-mRNA spliced forms in the human genome. One of the transcripts con- tains an HERV-H LTR that could affect the expression level of DYX1C1. We speculate that the HERV-H LTR integrated into the DYX1C1 locus in the catar- rhine lineage after its divergence from the platyrrhine lineage. Reverse tran- scription-PCR of the HERV-H LTR-related transcript produced four alternative forms from several human tissues. All of alternative forms were also identified in various rhesus macaque tissues. Through sequencing analysis of various pri- mate DNA samples, we found that a part of the HERV-H LTR sequence was dupli- cated within the DYX1C1 exon 9 only in catarrhines. However, the duplication event did not cause frameshift mutation of the DYX1C1 transcript. Taken together, this HERV-H LTR insertion into DYX1C1 has contributed to transcript diversification of DYX1C1 during primate evolution. -
Genome-Wide Association Scan Identifies New Variants Associated
Gialluisi et al. Translational Psychiatry (2019) 9:77 https://doi.org/10.1038/s41398-019-0402-0 Translational Psychiatry ARTICLE Open Access Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia Alessandro Gialluisi 1,2,3, Till F. M. Andlauer 1,2, Nazanin Mirza-Schreiber1,KristinaMoll4, Jessica Becker5,6, Per Hoffmann 5,6, Kerstin U. Ludwig 5,6,DarinaCzamara 1,BeateStPourcain 7,8,9, William Brandler10, Ferenc Honbolygó11,DénesTóth11,ValériaCsépe11, Guillaume Huguet12,13, Andrew P. Morris14,15, Jacqueline Hulslander16, Erik G. Willcutt16, John C. DeFries16,RichardK.Olson16, Shelley D. Smith17, Bruce F. Pennington18, Anniek Vaessen19,UrsMaurer20, Heikki Lyytinen21, Myriam Peyrard-Janvid22, Paavo H. T. Leppänen21, Daniel Brandeis23,24,25,26, Milene Bonte19,JohnF.Stein 27,JoelB.Talcott 28, Fabien Fauchereau12,13, Arndt Wilcke29,ClydeFrancks7,8, Thomas Bourgeron12,13, Anthony P. Monaco15,30, Franck Ramus 31, Karin Landerl32,JuhaKere 22,33,34,ThomasS.Scerri15,35, Silvia Paracchini 36,SimonE.Fisher 7,8, Johannes Schumacher5,6,MarkusM.Nöthen5,6, Bertram Müller-Myhsok1,2,37 and Gerd Schulte-Körne4 Abstract Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468).