Clinical Relevance of Small Copy-Number Variants in Chromosomal Microarray Clinical Testing
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Nuclear and Mitochondrial Genome Defects in Autisms
UC Irvine UC Irvine Previously Published Works Title Nuclear and mitochondrial genome defects in autisms. Permalink https://escholarship.org/uc/item/8vq3278q Journal Annals of the New York Academy of Sciences, 1151(1) ISSN 0077-8923 Authors Smith, Moyra Spence, M Anne Flodman, Pamela Publication Date 2009 DOI 10.1111/j.1749-6632.2008.03571.x License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California THE YEAR IN HUMAN AND MEDICAL GENETICS 2009 Nuclear and Mitochondrial Genome Defects in Autisms Moyra Smith, M. Anne Spence, and Pamela Flodman Department of Pediatrics, University of California, Irvine, California In this review we will evaluate evidence that altered gene dosage and structure im- pacts neurodevelopment and neural connectivity through deleterious effects on synap- tic structure and function, and evidence that the latter are key contributors to the risk for autism. We will review information on alterations of structure of mitochondrial DNA and abnormal mitochondrial function in autism and indications that interactions of the nuclear and mitochondrial genomes may play a role in autism pathogenesis. In a final section we will present data derived using Affymetrixtm SNP 6.0 microar- ray analysis of DNA of a number of subjects and parents recruited to our autism spectrum disorders project. We include data on two sets of monozygotic twins. Col- lectively these data provide additional evidence of nuclear and mitochondrial genome imbalance in autism and evidence of specific candidate genes in autism. We present data on dosage changes in genes that map on the X chromosomes and the Y chro- mosome. -
AGAP1 (NM 014914) Human Recombinant Protein Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP314836 AGAP1 (NM_014914) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of human ArfGAP with GTPase domain, ankyrin repeat and PH domain 1 (AGAP1), transcript variant 2 Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 88.9 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_055729 Locus ID: 116987 UniProt ID: Q9UPQ3 RefSeq Size: 4078 Cytogenetics: 2q37.2 RefSeq ORF: 2412 Synonyms: AGAP-1; CENTG2; cnt-g2; GGAP1 Summary: This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011] This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 AGAP1 (NM_014914) Human Recombinant Protein – TP314836 Protein Pathways: Endocytosis Product images: Coomassie blue staining of purified AGAP1 protein (Cat# TP314836). -
Proteomics Provides Insights Into the Inhibition of Chinese Hamster V79
www.nature.com/scientificreports OPEN Proteomics provides insights into the inhibition of Chinese hamster V79 cell proliferation in the deep underground environment Jifeng Liu1,2, Tengfei Ma1,2, Mingzhong Gao3, Yilin Liu4, Jun Liu1, Shichao Wang2, Yike Xie2, Ling Wang2, Juan Cheng2, Shixi Liu1*, Jian Zou1,2*, Jiang Wu2, Weimin Li2 & Heping Xie2,3,5 As resources in the shallow depths of the earth exhausted, people will spend extended periods of time in the deep underground space. However, little is known about the deep underground environment afecting the health of organisms. Hence, we established both deep underground laboratory (DUGL) and above ground laboratory (AGL) to investigate the efect of environmental factors on organisms. Six environmental parameters were monitored in the DUGL and AGL. Growth curves were recorded and tandem mass tag (TMT) proteomics analysis were performed to explore the proliferative ability and diferentially abundant proteins (DAPs) in V79 cells (a cell line widely used in biological study in DUGLs) cultured in the DUGL and AGL. Parallel Reaction Monitoring was conducted to verify the TMT results. γ ray dose rate showed the most detectable diference between the two laboratories, whereby γ ray dose rate was signifcantly lower in the DUGL compared to the AGL. V79 cell proliferation was slower in the DUGL. Quantitative proteomics detected 980 DAPs (absolute fold change ≥ 1.2, p < 0.05) between V79 cells cultured in the DUGL and AGL. Of these, 576 proteins were up-regulated and 404 proteins were down-regulated in V79 cells cultured in the DUGL. KEGG pathway analysis revealed that seven pathways (e.g. -
Targeted Resequencing Identifies Genes with Recurrent Variation In
www.nature.com/npjgenmed ARTICLE OPEN Targeted resequencing identifies genes with recurrent variation in cerebral palsy C. L. van Eyk 1,2, M. A. Corbett 1,2, M. S. B. Frank 1,2, D. L. Webber1,2, M. Newman3, J. G. Berry 1,2, K. Harper1,2, B. P. Haines1,2, G. McMichael1,2, J. A. Woenig1,2, A. H. MacLennan1,2 and J. Gecz 1,2,4* A growing body of evidence points to a considerable and heterogeneous genetic aetiology of cerebral palsy (CP). To identify recurrently variant CP genes, we designed a custom gene panel of 112 candidate genes. We tested 366 clinically unselected singleton cases with CP, including 271 cases not previously examined using next-generation sequencing technologies. Overall, 5.2% of the naïve cases (14/271) harboured a genetic variant of clinical significance in a known disease gene, with a further 4.8% of individuals (13/271) having a variant in a candidate gene classified as intolerant to variation. In the aggregate cohort of individuals from this study and our previous genomic investigations, six recurrently hit genes contributed at least 4% of disease burden to CP: COL4A1, TUBA1A, AGAP1, L1CAM, MAOB and KIF1A. Significance of Rare VAriants (SORVA) burden analysis identified four genes with a genome-wide significant burden of variants, AGAP1, ERLIN1, ZDHHC9 and PROC, of which we functionally assessed AGAP1 using a zebrafish model. Our investigations reinforce that CP is a heterogeneous neurodevelopmental disorder with known as well as novel genetic determinants. npj Genomic Medicine (2019) ; https://doi.org/10.1038/s41525-019-0101-z4:27 1234567890():,; INTRODUCTION is likely also due in part to the stringent criteria used to select Cerebral palsy (CP) is the most common motor disability of causative variants. -
CTNS Molecular Genetics Profile in a Persian Nephropathic Cystinosis Population
n e f r o l o g i a 2 0 1 7;3 7(3):301–310 Revista de la Sociedad Española de Nefrología www.revistanefrologia.com Original article CTNS molecular genetics profile in a Persian nephropathic cystinosis population a b a a Farideh Ghazi , Rozita Hosseini , Mansoureh Akouchekian , Shahram Teimourian , a b c,d a,b,c,d,∗ Zohreh Ataei Kachoei , Hassan Otukesh , William A. Gahl , Babak Behnam a Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran b Department of Pediatrics, Faculty of Medicine, Ali Asghar Children Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran c Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA d NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, MD, USA a r t i c l e i n f o a b s t r a c t Article history: Purpose: In this report, we document the CTNS gene mutations of 28 Iranian patients with Received 26 May 2016 nephropathic cystinosis age 1–17 years. All presented initially with severe failure to thrive, Accepted 22 November 2016 polyuria, and polydipsia. Available online 24 February 2017 Methods: Cystinosis was primarily diagnosed by a pediatric nephrologist and then referred to the Iran University of Medical Sciences genetics clinic for consultation and molecular Keywords: analysis, which involved polymerase chain reaction (PCR) amplification to determine the Cystinosis presence or absence of the 57-kb founder deletion in CTNS, followed by direct sequencing CTNS of the coding exons of CTNS. -
Supplemental Material Placed on This Supplemental Material Which Has Been Supplied by the Author(S) J Med Genet
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Med Genet Supplement Supplementary Table S1: GENE MEAN GENE NAME OMIM SYMBOL COVERAGE CAKUT CAKUT ADTKD ADTKD aHUS/TMA aHUS/TMA TUBULOPATHIES TUBULOPATHIES Glomerulopathies Glomerulopathies Polycystic kidneys / Ciliopathies Ciliopathies / kidneys Polycystic METABOLIC DISORDERS AND OTHERS OTHERS AND DISORDERS METABOLIC x x ACE angiotensin-I converting enzyme 106180 139 x ACTN4 actinin-4 604638 119 x ADAMTS13 von Willebrand cleaving protease 604134 154 x ADCY10 adenylate cyclase 10 605205 81 x x AGT angiotensinogen 106150 157 x x AGTR1 angiotensin II receptor, type 1 106165 131 x AGXT alanine-glyoxylate aminotransferase 604285 173 x AHI1 Abelson helper integration site 1 608894 100 x ALG13 asparagine-linked glycosylation 13 300776 232 x x ALG9 alpha-1,2-mannosyltransferase 606941 165 centrosome and basal body associated x ALMS1 606844 132 protein 1 x x APOA1 apolipoprotein A-1 107680 55 x APOE lipoprotein glomerulopathy 107741 77 x APOL1 apolipoprotein L-1 603743 98 x x APRT adenine phosphoribosyltransferase 102600 165 x ARHGAP24 Rho GTPase-Activation protein 24 610586 215 x ARL13B ADP-ribosylation factor-like 13B 608922 195 x x ARL6 ADP-ribosylation factor-like 6 608845 215 ATPase, H+ transporting, lysosomal V0, x ATP6V0A4 605239 90 subunit a4 ATPase, H+ transporting, lysosomal x x ATP6V1B1 192132 163 56/58, V1, subunit B1 x ATXN10 ataxin -
Targeting PH Domain Proteins for Cancer Therapy
The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 12-2018 Targeting PH domain proteins for cancer therapy Zhi Tan Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Bioinformatics Commons, Medicinal Chemistry and Pharmaceutics Commons, Neoplasms Commons, and the Pharmacology Commons Recommended Citation Tan, Zhi, "Targeting PH domain proteins for cancer therapy" (2018). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 910. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/910 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. TARGETING PH DOMAIN PROTEINS FOR CANCER THERAPY by Zhi Tan Approval page APPROVED: _____________________________________________ Advisory Professor, Shuxing Zhang, Ph.D. _____________________________________________ -
Supplementary Materials
Supplementary Materials COMPARATIVE ANALYSIS OF THE TRANSCRIPTOME, PROTEOME AND miRNA PROFILE OF KUPFFER CELLS AND MONOCYTES Andrey Elchaninov1,3*, Anastasiya Lokhonina1,3, Maria Nikitina2, Polina Vishnyakova1,3, Andrey Makarov1, Irina Arutyunyan1, Anastasiya Poltavets1, Evgeniya Kananykhina2, Sergey Kovalchuk4, Evgeny Karpulevich5,6, Galina Bolshakova2, Gennady Sukhikh1, Timur Fatkhudinov2,3 1 Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russia 2 Laboratory of Growth and Development, Scientific Research Institute of Human Morphology, Moscow, Russia 3 Histology Department, Medical Institute, Peoples' Friendship University of Russia, Moscow, Russia 4 Laboratory of Bioinformatic methods for Combinatorial Chemistry and Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia 5 Information Systems Department, Ivannikov Institute for System Programming of the Russian Academy of Sciences, Moscow, Russia 6 Genome Engineering Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia Figure S1. Flow cytometry analysis of unsorted blood sample. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S2. Flow cytometry analysis of unsorted liver stromal cells. Representative forward, side scattering and histogram are shown. The proportions of negative cells were determined in relation to the isotype controls. The percentages of positive cells are indicated. The blue curve corresponds to the isotype control. Figure S3. MiRNAs expression analysis in monocytes and Kupffer cells. Full-length of heatmaps are presented. -
CTNS Gene Cystinosin, Lysosomal Cystine Transporter
CTNS gene cystinosin, lysosomal cystine transporter Normal Function The CTNS gene provides instructions for making a protein called cystinosin. This protein is located in the membrane of lysosomes, which are compartments in the cell that digest and recycle materials. Proteins digested inside lysosomes are broken down into smaller building blocks, called amino acids. The amino acids are then moved out of lysosomes by transport proteins. Cystinosin is a transport protein that specifically moves the amino acid cystine out of the lysosome. Health Conditions Related to Genetic Changes Cystinosis More than 80 different mutations that are responsible for causing cystinosis have been identified in the CTNS gene. The most common mutation is a deletion of a large part of the CTNS gene (sometimes referred to as the 57-kb deletion), resulting in the complete loss of cystinosin. This deletion is responsible for approximately 50 percent of cystinosis cases in people of European descent. Other mutations result in the production of an abnormally short protein that cannot carry out its normal transport function. Mutations that change very small regions of the CTNS gene may allow the transporter protein to retain some of its usual activity, resulting in a milder form of cystinosis. Other Names for This Gene • CTNS-LSB • CTNS_HUMAN • Cystinosis • PQLC4 Additional Information & Resources Tests Listed in the Genetic Testing Registry • Tests of CTNS (https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=1497[geneid]) Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1 Scientific Articles on PubMed • PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28CTNS%5BTIAB%5D%29+O R+%28Cystinosis%5BTIAB%5D%29+AND+%28Genes%5BMH%5D%29+AND+eng lish%5Bla%5D+AND+human%5Bmh%5D+AND+%22last+3600+days%22%5Bdp% 5D) Catalog of Genes and Diseases from OMIM • CYSTINOSIN (https://omim.org/entry/606272) Research Resources • ClinVar (https://www.ncbi.nlm.nih.gov/clinvar?term=CTNS[gene]) • NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/1497) References • Anikster Y, Shotelersuk V, Gahl WA. -
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. -
Exon Junction Complexes Can Have Distinct Functional Flavours To
www.nature.com/scientificreports OPEN Exon Junction Complexes can have distinct functional favours to regulate specifc splicing events Received: 9 November 2017 Zhen Wang1, Lionel Ballut2, Isabelle Barbosa1 & Hervé Le Hir1 Accepted: 11 June 2018 The exon junction complex (EJC) deposited on spliced mRNAs, plays a central role in the post- Published: xx xx xxxx transcriptional gene regulation and specifc gene expression. The EJC core complex is associated with multiple peripheral factors involved in various post-splicing events. Here, using recombinant complex reconstitution and transcriptome-wide analysis, we showed that the EJC peripheral protein complexes ASAP and PSAP form distinct complexes with the EJC core and can confer to EJCs distinct alternative splicing regulatory activities. This study provides the frst evidence that diferent EJCs can have distinct functions, illuminating EJC-dependent gene regulation. Te Exon Junction Complex (EJC) plays a central role in post-transcriptional gene expression control. EJCs tag mRNA exon junctions following intron removal by spliceosomes and accompany spliced mRNAs from the nucleus to the cytoplasm where they are displaced by the translating ribosomes1,2. Te EJC is organized around a core complex made of the proteins eIF4A3, MAGOH, Y14 and MLN51, and this EJC core serves as platforms for multiple peripheral factors during diferent post-transcriptional steps3,4. Dismantled during translation, EJCs mark a very precise period in mRNA life between nuclear splicing and cytoplasmic translation. In this window, EJCs contribute to alternative splicing5–7, intra-cellular RNA localization8, translation efciency9–11 and mRNA stability control by nonsense-mediated mRNA decay (NMD)12–14. At a physiological level, developmental defects and human pathological disorders due to altered expression of EJC proteins show that the EJC dosage is critical for specifc cell fate determinations, such as specifcation of embryonic body axis in drosophila, or Neural Stem Cells division in the mouse8,15,16. -
Human-Specific Gain of Function in a Developmental Enhancer
Human-Specific Gain of Function in a Developmental Enhancer Shyam Prabhakar,1* Axel Visel,1 Jennifer A. Akiyama,1 Malak Shoukry,1 Keith D. Lewis,1 Amy Holt,1 Ingrid Plajzer-Frick,1 Harris Morrison,2 David R. FitzPatrick,2 Veena Afzal,1 Len A. Pennacchio,1,3 Edward M. Rubin,1,3 James P. Noonan1 1 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA 2 MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK. 3 United States Department of Energy Joint Genome Institute, Walnut Creek, CA, USA Evolution … of News • Yale Researchers Find “Junk DNA” May Have Triggered Key Evolutionary Changes in Human Thumb and Foot ▫ Office of Public Affairs (Yale University), Sept 4 • “Junk DNA” key to human evolution? ▫ World Science, Sept 4 • Opposable Thumbs and Upright Walking Caused By "Junk DNA" ▫ Slashdot, Sept 7 • Junk DNA may have handed us a gripping future ▫ New Scientist, Sept 4 Or Revolution? • It's the junk that makes us human ▫ Nature (2006) • Accelerated Evolution of Conserved Noncoding Sequences in Humans ▫ Shyam Prabhakar, James P. Noonan, Svante Pääbo, Edward M. Rubin HACNS1 • Human-accelerated conserved non-coding sequence 1 • 546 bp region • Well-conserved among terrestrial mammals • 16 human- specific mutations (since chimpanzee) Experiment • Transgenic mouse assay • β-galactosidase (lacZ) reporter gene • Minimal Hsp68 promoter • 1.2 kb fragment encompassing HACNS1 ▫ Human, Chimp, Rhesus In Vivo Results (E11.5) Reproducibility In Vivo (E13.5) Money Shot “Humanized” Element • Synthesize chimeric element with