POLR1B and Neural Crest Cell Anomalies in Treacher Collins Syndrome Type 4
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Essential Genes and Their Role in Autism Spectrum Disorder
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Essential Genes And Their Role In Autism Spectrum Disorder Xiao Ji University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Bioinformatics Commons, and the Genetics Commons Recommended Citation Ji, Xiao, "Essential Genes And Their Role In Autism Spectrum Disorder" (2017). Publicly Accessible Penn Dissertations. 2369. https://repository.upenn.edu/edissertations/2369 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2369 For more information, please contact [email protected]. Essential Genes And Their Role In Autism Spectrum Disorder Abstract Essential genes (EGs) play central roles in fundamental cellular processes and are required for the survival of an organism. EGs are enriched for human disease genes and are under strong purifying selection. This intolerance to deleterious mutations, commonly observed haploinsufficiency and the importance of EGs in pre- and postnatal development suggests a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication and repetitive behavior. More and more genetic evidence points to a polygenic model of ASD and it is estimated that hundreds of genes contribute to ASD. The central question addressed in this dissertation is whether genes with a strong effect on survival and fitness (i.e. EGs) play a specific oler in ASD risk. I compiled a comprehensive catalog of 3,915 mammalian EGs by combining human orthologs of lethal genes in knockout mice and genes responsible for cell-based essentiality. -
POLR1D Gene RNA Polymerase I and III Subunit D
POLR1D gene RNA polymerase I and III subunit D Normal Function The POLR1D gene provides instructions for making one part (subunit) of two related enzymes called RNA polymerase I and RNA polymerase III. These enzymes are involved in the production (synthesis) of ribonucleic acid (RNA), a chemical cousin of DNA. Both enzymes help synthesize a form of RNA known as ribosomal RNA (rRNA). RNA polymerase III also plays a role in the synthesis of several other forms of RNA, including transfer RNA (tRNA). Ribosomal RNA and transfer RNA assemble protein building blocks (amino acids) into functioning proteins, which is essential for the normal functioning and survival of cells. Based on its involvement in Treacher Collins syndrome, the POLR1D gene appears to play a critical role in the early development of structures that become bones and other tissues of the face. Health Conditions Related to Genetic Changes Treacher Collins syndrome At least 20 mutations in the POLR1D gene have been identified in people with Treacher Collins syndrome, a condition that affects the development of bones and other tissues of the face. These mutations appear to alter the structure and function of the POLR1D protein, which reduces the amount of functional RNA polymerase I and RNA polymerase III in cells. Consequently, less rRNA is produced. Researchers speculate that a shortage of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the early development of facial bones and tissues. The abnormal cell death could underlie the specific problems with facial development found in Treacher Collins syndrome. However, it is unclear why the effects of a reduction in rRNA are limited to facial development. -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Supporting Information
Supporting Information Pratilas et al. 10.1073/pnas.0900780106 SI Text HER2) xenografts. In each of these analyses, all noncontrol Determination of Sensitivity to MEK Inhibition. Drug sensitivity probes (n ϭ 22,215) were rank-ordered according to the mag- assays were performed by using a 96-well plate and the Alamar nitude of their difference in expression after MEK inhibition Blue reagent (Invitrogen) as reported (1). The cells were treated compared with DMSO-treated controls, as measured by SAM- with PD0325901 (Pfizer) in a range of concentrations from 0.1 derived d-scores. The positions of the output genes in this signed to 500 nM (Fig. S1). ranking were then scored in a manner similar to that described by the Connectivity Map (2). This empirical and nonparametric Enrichment Analysis Over a Time Course of MEK Inhibition. Af- Kolmogorov-Smirnov-based statistic reflects an enrichment fymetrix U133A 2.0 array analysis of V600EBRAF, SkMel-28 cells, score that ranges from ϩ1toϪ1, where a score of 0 is a lack of at 0, 2, 8, and 24 h after MEK inhibition was completed as enrichment in either direction of expression, or graphically, a described (see Experimental Procedures). Robust multiarray av- random distribution of the output profile genes. Those with erage (RMA) was used to estimate the expression of probe sets. enrichment scores nearer to 1 indicated increasing correlation Each time point from2hto24wascompared with 0 h, and in between the output profile and the rank-ordered gene set from each comparison, we considered only probe sets with an expres- the experimental comparison. -
Abstracts from the 51St European Society of Human Genetics Conference: Electronic Posters
European Journal of Human Genetics (2019) 27:870–1041 https://doi.org/10.1038/s41431-019-0408-3 MEETING ABSTRACTS Abstracts from the 51st European Society of Human Genetics Conference: Electronic Posters © European Society of Human Genetics 2019 June 16–19, 2018, Fiera Milano Congressi, Milan Italy Sponsorship: Publication of this supplement was sponsored by the European Society of Human Genetics. All content was reviewed and approved by the ESHG Scientific Programme Committee, which held full responsibility for the abstract selections. Disclosure Information: In order to help readers form their own judgments of potential bias in published abstracts, authors are asked to declare any competing financial interests. Contributions of up to EUR 10 000.- (Ten thousand Euros, or equivalent value in kind) per year per company are considered "Modest". Contributions above EUR 10 000.- per year are considered "Significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal Genetics then compared this data to de novo cases where research based PO studies were completed (N=57) in NY. E-P01.01 Results: MFSIQ (66.4) for familial deletions was Parent of origin in familial 22q11.2 deletions impacts full statistically lower (p = .01) than for de novo deletions scale intelligence quotient scores (N=399, MFSIQ=76.2). MFSIQ for children with mater- nally inherited deletions (63.7) was statistically lower D. E. McGinn1,2, M. Unolt3,4, T. B. Crowley1, B. S. Emanuel1,5, (p = .03) than for paternally inherited deletions (72.0). As E. H. Zackai1,5, E. Moss1, B. Morrow6, B. Nowakowska7,J. compared with the NY cohort where the MFSIQ for Vermeesch8, A. -
The Roles of RNA Polymerase I and III Subunits Polr1a, Polr1c, and Polr1d in Craniofacial Development BY
The roles of RNA Polymerase I and III subunits Polr1a, Polr1c, and Polr1d in craniofacial development BY © 2016 Kristin Emily Noack Watt Submitted to the graduate degree program in Anatomy and Cell Biology and to the Graduate Faculty of The University of Kansas Medical Center in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Paul Trainor, Co-Chairperson Brenda Rongish, Co-Chairperson Brian Andrews Jennifer Gerton Tatjana Piotrowski Russell Swerdlow Date Defended: January 26, 2016 The Dissertation Committee for Kristin Watt certifies that this is the approved version of the following dissertation: The roles of RNA Polymerase I and III subunits Polr1a, Polr1c, and Polr1d in craniofacial development Paul Trainor, Co-Chairperson Brenda Rongish, Co-Chairperson Date approved: February 2, 2016 ii Abstract Craniofacial anomalies account for approximately one-third of all birth defects. Two examples of syndromes associated with craniofacial malformations are Treacher Collins syndrome and Acrofacial Dysostosis, Cincinnati type which have phenotypic overlap including deformities of the eyes, ears, and facial bones. Mutations in TCOF1, POLR1C or POLR1D may cause Treacher Collins syndrome while mutations in POLR1A may cause Acrofacial Dysostosis, Cincinnati type. TCOF1 encodes the nucleolar phosphoprotein Treacle, which functions in rRNA transcription and modification. Previous studies demonstrated that Tcof1 mutations in mice result in reduced ribosome biogenesis and increased neuroepithelial apoptosis. This diminishes the neural crest cell (NCC) progenitor population which contribute to the development of the cranial skeleton. In contrast, apart from being subunits of RNA Polymerases (RNAP) I and/or III, nothing is known about the function of POLR1A, POLR1C, and POLR1D during embryonic and craniofacial development. -
Downloaded from and Have Previously Been Described in Detail [51; 52]
CpG island structure and trithorax/ polycomb chromatin domains in human cells The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Orlando, David A., Matthew G. Guenther, Garrett M. Frampton, and Richard A. Young. “CpG Island Structure and Trithorax/ polycomb Chromatin Domains in Human Cells.” Genomics 100, no. 5 (November 2012): 320–326. As Published http://dx.doi.org/10.1016/j.ygeno.2012.07.006 Publisher Elsevier Version Final published version Citable link http://hdl.handle.net/1721.1/101286 Terms of Use Creative Commons Attribution-Noncommercial-NoDerivatives Detailed Terms http://creativecommons.org/licenses/by-nc-nd/4.0/ NIH Public Access Author Manuscript Genomics. Author manuscript; available in PMC 2013 November 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Genomics. 2012 November ; 100(5): 320–326. doi:10.1016/j.ygeno.2012.07.006. CpG Island Structure and Trithorax/Polycomb Chromatin Domains in Human Cells David A. Orlando1,*, Matthew G. Guenther1,*, Garrett M. Frampton1,2,*, and Richard A. Young1,2,† 1Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA 2Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Abstract TrxG and PcG complexes play key roles in the epigenetic regulation of development through H3K4me3 and H3K27me3 modification at specific sites throughout the human genome, but how these sites are selected is poorly understood. We find that in pluripotent cells, clustered CpG- islands at genes predict occupancy of H3K4me3 and H3K27me3, and these “bivalent” chromatin domains precisely span the boundaries of CpG-island clusters. -
"The Genecards Suite: from Gene Data Mining to Disease Genome Sequence Analyses". In: Current Protocols in Bioinformat
The GeneCards Suite: From Gene Data UNIT 1.30 Mining to Disease Genome Sequence Analyses Gil Stelzer,1,5 Naomi Rosen,1,5 Inbar Plaschkes,1,2 Shahar Zimmerman,1 Michal Twik,1 Simon Fishilevich,1 Tsippi Iny Stein,1 Ron Nudel,1 Iris Lieder,2 Yaron Mazor,2 Sergey Kaplan,2 Dvir Dahary,2,4 David Warshawsky,3 Yaron Guan-Golan,3 Asher Kohn,3 Noa Rappaport,1 Marilyn Safran,1 and Doron Lancet1,6 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel 2LifeMap Sciences Ltd., Tel Aviv, Israel 3LifeMap Sciences Inc., Marshfield, Massachusetts 4Toldot Genetics Ltd., Hod Hasharon, Israel 5These authors contributed equally to the paper 6Corresponding author GeneCards, the human gene compendium, enables researchers to effectively navigate and inter-relate the wide universe of human genes, diseases, variants, proteins, cells, and biological pathways. Our recently launched Version 4 has a revamped infrastructure facilitating faster data updates, better-targeted data queries, and friendlier user experience. It also provides a stronger foundation for the GeneCards suite of companion databases and analysis tools. Improved data unification includes gene-disease links via MalaCards and merged biological pathways via PathCards, as well as drug information and proteome expression. VarElect, another suite member, is a phenotype prioritizer for next-generation sequencing, leveraging the GeneCards and MalaCards knowledgebase. It au- tomatically infers direct and indirect scored associations between hundreds or even thousands of variant-containing genes and disease phenotype terms. Var- Elect’s capabilities, either independently or within TGex, our comprehensive variant analysis pipeline, help prepare for the challenge of clinical projects that involve thousands of exome/genome NGS analyses. -
2Q13 Microdeletions
2q13 microdeletions rarechromo.org 2q13 microdeletions A 2q13 microdeletion is a rare genetic condition caused by a small piece of missing genetic material from one of the body’s chromosomes - chromosome 2. Deletions can vary in size but those that are too small to be visible under the microscope using standard techniques are called microdeletions. For typical and healthy development, chromosomes should contain the expected amount of genetic material. Like most other chromosome disorders, having a missing piece of chromosome 2 may affect the development and intellectual abilities of a child. The outcome of having a 2q13 microdeletion is very variable and depends on a number of factors including what and how much genetic material is missing. Background on chromosomes Our bodies are made up of different types of cells, almost all of which contain the same chromosomes. Each chromosome consists of DNA that carries the code for hundreds to thousands of genes. Genes can be thought of as individual instruction booklets (or recipes) that contain all the genetic information that tells the body how to develop, grow and function. Chromosomes (and hence genes) usually come in pairs with one member of each chromosome pair being inherited from each parent. Most cells of the human body have a total of 46 (23 pairs of) chromosomes. The egg and the sperm cells, however, have 23 unpaired chromosomes, so that when the egg and sperm join together at conception, the chromosomes pair up to make a total of 46. Of these 46 chromosomes, 44 are grouped in 22 pairs, numbered 1 to 22. -
2Q13 Microduplications
2q13 microduplications rarechromo.org 2q13 microduplications A 2q13 microduplication is a rare genetic condition caused by a small piece of extra genetic material from one of the body’s chromosomes - chromosome 2. Duplications can vary in size but those that are too small to be visible under the microscope using standard techniques are called microduplications. For typical and healthy development, chromosomes should contain the expected amount of genetic material. Like most other chromosome disorders, having an extra piece of chromosome 2 may affect the development and intellectual abilities of a child. The outcome of having a 2q13 microduplication is very variable and depends on a number of factors including what and how much genetic material is duplicated. Background on chromosomes Our bodies are made up of different types of cells, almost all of which contain the same chromosomes. Each chromosome consists of DNA that carries the code for hundreds to thousands of genes. Genes can be thought of as individual instruction booklets (or recipes) that contain all the genetic information that tells the body how to develop, grow and function. Chromosomes (and hence genes) usually come in pairs with one member of each chromosome pair being inherited from each parent. Most cells of the human body have a total of 46 (23 pairs of) chromosomes. The egg and the sperm cells, however, have 23 unpaired chromosomes, so that when the egg and sperm join together at conception, the chromosomes pair up to make 46 in total. Of these 46 chromosomes, 44 are grouped in 22 pairs, numbered 1 to 22. -
Combined Genome, Transcriptome and Metabolome Analysis in the Diagnosis of Childhood Cerebellar Ataxia
International Journal of Molecular Sciences Article Combined Genome, Transcriptome and Metabolome Analysis in the Diagnosis of Childhood Cerebellar Ataxia Ana Ching-López 1,2 , Luis Javier Martinez-Gonzalez 3 , Luisa Arrabal 4, Jorge Sáiz 5, Ángela Gavilán 6, Coral Barbas 5 , Jose Antonio Lorente 3,7, Susana Roldán 4, Maria José Sánchez 1,2,8,*,† and Purificacion Gutierrez-Ríos 8,† 1 CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; [email protected] 2 Andalusian School of Public Health (EASP), 18080 Granada, Spain 3 GENYO, Centre for Genomics and Oncological Research, Pfizer, University of Granada, Andalusian Regional Government, PTS Granada, 18016 Granada, Spain; [email protected] (L.J.M.-G.); [email protected] (J.A.L.) 4 Pediatric Neurology Department, Hospital Virgen de las Nieves, 18014 Granada, Spain; [email protected] (L.A.); [email protected] (S.R.) 5 Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty, Universidad San Pablo-CEU, 28925 Madrid, Spain; [email protected] (J.S.); [email protected] (C.B.) 6 Institute of Biomedicine of Seville (IBIS), 41013 Seville, Spain; [email protected] 7 Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine-PTS, University of Granada, 18016 Granada, Spain 8 Citation: Ching-López, A.; Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain; Martinez-Gonzalez, L.J.; Arrabal, L.; purifi[email protected] Sáiz, J.; Gavilán, Á.; Barbas, C.; * Correspondence: [email protected] † These authors have contributed equally. Lorente, J.A.; Roldán, S.; Sánchez, M.J.; Gutierrez-Ríos, P. Combined Genome, Transcriptome and Abstract: Ataxia in children is a common clinical sign of numerous neurological disorders consisting Metabolome Analysis in the of impaired coordination of voluntary muscle movement. -
A Novel Familial Mutation Associated with Treacher Collins Syndrome: a Case Report
BIOMEDICAL REPORTS 12: 285-289, 2020 A novel familial mutation associated with Treacher Collins syndrome: A case report ELENA PAPAGEORGIOU1, IOANNIS PAPOULIDIS1, APOSTOLOS ZAVLANOS2, EVAGGELOS PAPANIKOLAOU3, EMMANOUIL MANOLAKOS1 and STILIANI FIDANI4 1Access to Genome, Clinical Laboratory Genetics, 55134 Thessaloniki; 21st Department of Obstetrics and Gynecology, Papageorgiou Hospital, 56403 Thessaloniki; 33rd Department of Obstetrics and Gynecology, Ippokratio Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki; 4Department for Special Needs, Aristotle University of Thessaloniki Achepa Hospital, 54636 Thessaloniki, Greece Received February 7, 2019; Accepted October 21, 2019 DOI: 10.3892/br.2020.1284 Abstract. Treacher Collins syndrome (TCS) is a type of the condition came from Thomson in 1849 (2) and Berry in mandibulofacial dysostosis with incomplete penetrance and 1889 (3), but the condition is officially named after E. Treacher high intra- and interfamilial clinical heterogeneity, and it is Collins, who described the diagnostic criteria of this disease associated with mutations of treacle ribosome biogenesis in 1900 (4). A more detailed description of the syndrome was factor 1 (TCOF1), and RNA polymerase I and III subunit provided by Franceshetti and Klein in 1949, who used the (POLR1)C and POLR1D genes. In the present case report, term MFD, and subsequently TCS was also referred to as a patient with TCS with auricle dysplasia and hearing Franceshetti-Klein syndrome (4). loss accompanied with intellectual disability is described. TCS is characterized by symmetrical malformations with Sequence analysis was performed on blood samples from variable clinical features. Some typical characteristics of the the patient and his father via oligonucleotide-based target disease are down‑slanting palpebral fissures, hypoplastic zygo- capture, followed by next-generation sequencing.