DOCSLIB.ORG

THE IMPORTANT ROLE of GENETIC SCREENING Making the Best Decisions for You and Your Family

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
THE IMPORTANT ROLE of GENETIC SCREENING Making the Best Decisions for You and Your Family THE IMPORTANT ROLE OF GENETIC SCREENING Making the best decisions for you and your family A VARIETY OF SCREENING METHODS ARE USED TO DETERMINE RISK DURING PREGNANCY Noninvasive prenatal screening Chromosome conditions Carrier screening Inherited conditions Serum screening Ultrasound Hormone and protein levels Anatomical abnormalities associated with birth defects MORE INFO Screening overview Genetic screening Noninvasive prenatal screening Carrier screening Complementary Screens During Pregnancy Screening vs. Diagnostic Tests • Several different types of screening tests are offered during • Screening tests are different than diagnostic tests pregnancy • Screening tests do not give definitive answers. Instead, they • Each is performed with the goal of assessing for risks and provide information about whether there is an increased complications in the pregnancy chance of a problem being present • Some routine screening tests done during pregnancy • Diagnostic tests, such as chorionic villus sampling (CVS) or include: carrier screening, noninvasive prenatal screening amniocentesis, are available to provide definitive information using cell-free DNA, ultrasound and maternal serum screening • Screening tests are done at different points during pregnancy and for different purposes Carrier screening and noninvasive prenatal screening, two genetic screens done early PRENATAL SCREENING on, can inform the care of your pregnancy and baby. Noninvasive prenatal screening can help avoid the need for invasive IN EARLY PREGNANCY diagnostic tests (indicated by below). * * Carrier Screening Carrier Screening Dating Scan (Ultrasound) Noninvasive Prenatal Screening 1st Trimester Maternal Serum Screen Nuchal Translucency Ultrasound 1st TR BEFORE IME Chorionic Villus Sampling STE R 2nd Trimester Maternal Serum Screen Anatomy Scan (Ultrasound) 2 Amniocentesis n d *Can be done before T or early in pregnancy R I M E MORE INFO S T E R Screening overview Genetic screening Noninvasive prenatal screening Carrier screening Screening Tests • Screening tests are different than diagnostic tests • Screening tests do not give definitive answers. Instead, they provide information about whether there is an increased chance of a problem being present Carrier Screening Noninvasive Prenatal Screening • Ideally done preconception, but can be done during pregnancy • Done using a standard blood draw from the mother’s arm • Looks for irregularities, called mutations, in the mother’s and/or as early as 10 weeks father’s genes that can be passed down to a child • Assesses risk for chromosome conditions, including Down • In most cases both mother and father need to be carriers for the same syndrome and other more severe conditions condition for their children to be at risk of developing symptoms • Chromosome conditions generally happen by chance, instead of being inherited from the parents Dating Scan (Ultrasound) • Usually done at first prenatal visit 1st and 2nd Trimester Maternal Serum Screening • Performed at ~10-14 weeks and then at ~15-20 weeks • Sound waves are used to visualize the developing baby (this is completely safe!) • Estimates the chance for chromosome conditions and birth defects of the spine • Confirms a heartbeat – Looks at a variety of proteins in the mother’s blood – May include a nuchal translucency ultrasound Anatomy Scan (Ultrasound) • Performed at ~18-20 weeks • Used to check normal growth and development of the baby Invasive Diagnostic Tests • Diagnostic tests, such as chorionic villus sampling (CVS) or amniocentesis, are available to provide definitive information Chorionic Villus Sampling (CVS) Amniocentesis • Performed between 10 and 14 weeks • Generally performed between 16 and 22 weeks • Using ultrasound guidance, a small sample of the placenta is removed • A small sample of fluid is taken from the uterus without touching and analyzed the baby • There is a risk of miscarriage with this procedure, but this risk is less • Fetal cells in the fluid are analyzed to look for certain kinds of than 1% (less than 1 in 100) abnormalities, while the fluid itself is analyzed for certain proteins • There is a risk of miscarriage with this procedure, but this risk is less than 0.5% (less than 1 in 200) GENETIC SCREENS ARE LIKE ULTRASOUNDS FOR DNA Noninvasive Carrier screening prenatal screening Determines baby’s risk of having Determines risk of baby having a condition passed down from a chromosome condition the mother and father Cells Chromosomes DNA Genes MORE INFO Screening overview Genetic screening Noninvasive prenatal screening Carrier screening Cells DNA • The human body contains trillions of cells • Chromosomes are made up of tightly packed DNA • Cells in different parts of the body have different functions, • DNA consists of bases named A,C,T and G but with only a few exceptions every cell contains the same • DNA is like the blueprint for a person genetic information Chromosomes Genes • Most of the genetic information in each cell is located in • Small segments of DNA that act as the recipes for individual the nucleus. It is organized into compact chunks called proteins are called genes chromosomes • The genes babies inherit from their parents pass along family • Typically cells contain 46 total chromosomes, organized into characteristics like hair and eye color. Sometimes they also 23 pairs pass on genetic diseases, even if the parents don’t have any • One member of each pair of chromosomes comes from the symptoms mother, and the other comes from the father • Carrier screening is used to determine if prospective parents • Noninvasive prenatal screening is used to determine if by carry mutations in genes that could cause an inherited chance there are any extra or missing chromosomes in a condition pregnancy CHROMOSOME CONDITIONS CAN HAVE VARYING OUTCOMES 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y Normally cells contain 23 pairs of chromosomes Trisomy Screening is also available for: A trisomy occurs when the cells of the body Sex chromosomes contain an extra chromosome Sometimes there may be too many or too few This screen can also determine the sex of the baby Trisomy 21 Down syndrome Trisomy 18 Edwards syndrome Microdeletions Trisomy 13 Patau syndrome In rare cases, a tiny piece of a chromosome is missing MORE INFO Screening overview Genetic screening Noninvasive prenatal screening Carrier screening Trisomies Trisomy 18: Edwards Syndrome • Typically cells contain 46 total chromosomes, organized into 23 • Individuals with Edwards syndrome have an extra copy of pairs. One member of each pair comes from the mother, and the chromosome 18 other comes from the father • Health problems in babies born with Edwards syndrome • Trisomic conditions occur when an individual has a total number are usually life-threatening, including heart defects and of 47 chromosomes, instead of the typical 46. This excess genetic breathing difficulties material can lead to specific conditions, depending on which • Edwards syndrome occurs in about 1 in 5,000 live births. chromosomal pair has an extra chromosome Miscarriages are common with affected pregnancies Trisomy 21: Down Syndrome Trisomy 13: Patau Syndrome • Individuals with Down syndrome have an extra copy of • Individuals with Patau syndrome have an extra copy of chromosome 21 chromosome 13 • People with Down syndrome typically have mild to moderate • Patau syndrome causes life-threatening birth defects and intellectual disability and may also have additional health conditions severe intellectual disability • Outcomes for people with Down syndrome have improved • Patau syndrome occurs in about 1 in 10,000 live births. significantly in the past 40 years with increased access to education, Miscarriages are common with affected pregnancies social supports, employment opportunities, and family support • Down syndrome occurs in about 1 in 800 live births Sex Chromosome Differences Microdeletions • The sex chromosomes determine whether the baby will be male • In addition to changes in the number of chromosomes (e.g., (XY) or female (XX) trisomies), there can be changes in the structure of the • Sometimes there may be too many or too few sex chromosomes, chromosomes resulting in potential health issues • Sometimes small pieces of genetic material are missing. This • In addition to assessing whether there are extra or missing sex is called a microdeletion chromosomes, noninvasive prenatal screening can also determine • Microdeletions can lead to developmental challenges and the sex of the baby health issues HOW IT WORKS Simple blood draw from the mother’s arm causing no risk to her or the pregnancy Maternal blood stream Red blood cell Maternal DNA Placental DNA Normal developmental processes cause small pieces of DNA from placenta to enter mother’s bloodstream. Analyzing these DNA fragments can indicate risk of chromosome conditions. MORE INFO Screening overview Genetic screening Noninvasive prenatal screening Carrier screening What is Cell-free DNA? Cell-free DNA is Used for Screening, Not Diagnosis • Normal developmental processes cause small pieces of DNA • Screening tests do not give definitive answers. Instead, they from the baby’s placenta to enter the mother’s bloodstream provide information about whether there is an increased • These fragments are called cell-free DNA chance of a problem being present • Noninvasive prenatal screening uses cell-free DNA to help • Diagnostic tests, such as chorionic villus sampling (CVS) or determine if a pregnancy is at heightened risk for a common amniocentesis,
Load more

Recommended publications
  • Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
    Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A.
    [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]
  • (Lcrs) in 22Q11 Mediate Deletions, Duplications, Translocations, and Genomic Instability: an Update and Literature Review Tamim H
    review January/February 2001 ⅐ Vol. 3 ⅐ No. 1 Evolutionarily conserved low copy repeats (LCRs) in 22q11 mediate deletions, duplications, translocations, and genomic instability: An update and literature review Tamim H. Shaikh, PhD1, Hiroki Kurahashi, MD, PhD1, and Beverly S. Emanuel, PhD1,2 Several constitutional rearrangements, including deletions, duplications, and translocations, are associated with 22q11.2. These rearrangements give rise to a variety of genomic disorders, including DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes (DGS/VCFS/CAFS), cat eye syndrome (CES), and the supernumerary der(22)t(11;22) syndrome associated with the recurrent t(11;22). Chromosome 22-specific duplications or low copy repeats (LCRs) have been directly implicated in the chromosomal rearrangements associated with 22q11.2. Extensive sequence analysis of the different copies of 22q11 LCRs suggests a complex organization. Examination of their evolutionary origin suggests that the duplications in 22q11.2 may predate the divergence of New World monkeys 40 million years ago. Based on the current data, a number of models are proposed to explain the LCR-mediated constitutional rearrangements of 22q11.2. Genetics in Medicine, 2001:3(1):6–13. Key Words: duplication, evolution, 22q11, deletion and translocation Although chromosome 22 represents only 2% of the haploid The 22q11.2 deletion syndrome, which includes DGS/ human genome,1 recurrent, clinically significant, acquired, VCFS/CAFS, is the most common microdeletion syndrome. and somatic
    [Show full text]
  • Molecular Structure and Physiological Function of Chloride Channels
    Physiol Rev 82: 503–568, 2002; 10.1152/physrev.00029.2001. Molecular Structure and Physiological Function of Chloride Channels THOMAS J. JENTSCH, VALENTIN STEIN, FRANK WEINREICH, AND ANSELM A. ZDEBIK Zentrum fu¨r Molekulare Neurobiologie Hamburg, Universita¨t Hamburg, Hamburg, Germany I. Introduction 504 II. Cellular Functions of Chloride Channels 506 A. Plasma membrane channels 506 B. Channels of intracellular organelles 507 III. The CLC Chloride Channel Family 508 A. General features of CLC channels 510 B. ClC-0: the Torpedo electric organ ClϪ channel 516 C. ClC-1: a muscle-specific ClϪ channel that stabilizes the membrane voltage 517 D. ClC-2: a broadly expressed channel activated by hyperpolarization, cell swelling, and acidic pH 519 Ϫ E. ClC-K/barttin channels: Cl channels involved in transepithelial transport in the kidney and the Downloaded from inner ear 523 F. ClC-3: an intracellular ClϪ channel that is present in endosomes and synaptic vesicles 525 G. ClC-4: a poorly characterized vesicular channel 527 H. ClC-5: an endosomal channel involved in renal endocytosis 527 I. ClC-6: an intracellular channel of unknown function 531 J. ClC-7: a lysosomal ClϪ channel whose disruption leads to osteopetrosis in mice and humans 531 K. CLC proteins in model organisms 532 on October 3, 2014 IV. Cystic Fibrosis Transmembrane Conductance Regulator: a cAMP-Activated Chloride Channel 533 A. Structure and function of the CFTR ClϪ channel 533 B. Cellular regulation of CFTR activity 534 C. CFTR as a regulator of other ion channels 534 V. Swelling-Activated Chloride Channels 535 A. Biophysical characteristics of swelling-activated ClϪ currents 536 B.
    [Show full text]
  • Ophthalmic Phenotype of TCIRG1 Gene Mutations in Chinese Infantile Malignant Osteopetrosis
    BMJ Open Ophth: first published as 10.1136/bmjophth-2018-000180 on 17 November 2018. Downloaded from Original articles Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis Wenhong Cao,1,2 Wenbin Wei,2 Qian Wu1 To cite: Cao W, Wei W, Wu Q. ABSTRACT Key messages Ophthalmic phenotype of Objective To evaluate the ophthalmic phenotypes TCIRG1 gene mutations associated with T-cell immune regulator 1 (TCIRG1) What is already known about this subject? in Chinese infantile mutations in Chinese patients with infantile malignant malignant osteopetrosis. T-cell immune regulator 1 (TCIRG1) is one of the osteopetrosis (IMO). ► BMJ Open Ophthalmology main genes that are responsible for the majority of Methods and analysis 27 Chinese TCIRG1-related 2018;3:e000180. doi:10.1136/ infantile malignant osteopetrosis (IMO) cases, which osteoporosis infants were enrolled using direct DNA bmjophth-2018-000180 are characterised by neonatal and infantile onset, a sequencing of PCR-amplified exons. 12 cases had systemic sclerosis of bones, vulnerability to fracture, frameshift mutation (the frameshift mutation group, group progressive anaemia, infection, hepatosplenomega- Received 30 May 2018 F), and 15 cases had point mutation (the point mutation ly and cranial nerve dysfunction, including poor gaze Revised 25 September 2018 group, group P). The clinical features of the two groups qualities, optic atrophy and optic canal stenosis. Accepted 26 September 2018 were compared, including age at onset, gaze qualities, To our knowledge, there is no study on the ophthal- optic atrophy, optic canal stenosis and waveforms of Flash ► mic phenotypes of TCIRG1 mutations in patients visual-evoked potential (FVEP).
    [Show full text]
  • Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .
    [Show full text]
  • Transcriptomic and Proteomic Profiling Provides Insight Into
    BASIC RESEARCH www.jasn.org Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy † † ‡ Peidi Liu,* Emelie Lassén,* Viji Nair, Celine C. Berthier, Miyuki Suguro, Carina Sihlbom,§ † | † Matthias Kretzler, Christer Betsholtz, ¶ Börje Haraldsson,* Wenjun Ju, Kerstin Ebefors,* and Jenny Nyström* *Department of Physiology, Institute of Neuroscience and Physiology, §Proteomics Core Facility at University of Gothenburg, University of Gothenburg, Gothenburg, Sweden; †Division of Nephrology, Department of Internal Medicine and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan; ‡Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; |Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; and ¶Integrated Cardio Metabolic Centre, Karolinska Institutet Novum, Huddinge, Sweden ABSTRACT IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type–specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell–positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell–positive standard genes.
    [Show full text]
  • Chloride Channels Regulate Differentiation and Barrier Functions
    RESEARCH ARTICLE Chloride channels regulate differentiation and barrier functions of the mammalian airway Mu He1†*, Bing Wu2†, Wenlei Ye1, Daniel D Le2, Adriane W Sinclair3,4, Valeria Padovano5, Yuzhang Chen6, Ke-Xin Li1, Rene Sit2, Michelle Tan2, Michael J Caplan5, Norma Neff2, Yuh Nung Jan1,7,8, Spyros Darmanis2*, Lily Yeh Jan1,7,8* 1Department of Physiology, University of California, San Francisco, San Francisco, United States; 2Chan Zuckerberg Biohub, San Francisco, United States; 3Department of Urology, University of California, San Francisco, San Francisco, United States; 4Division of Pediatric Urology, University of California, San Francisco, Benioff Children’s Hospital, San Francisco, United States; 5Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Heaven, United States; 6Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, United States; 7Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; 8Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States *For correspondence: Abstract The conducting airway forms a protective mucosal barrier and is the primary target of [email protected] (MH); [email protected] airway disorders. The molecular events required for the formation and function of the airway (SD); mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway [email protected] (LYJ) diseases,
    [Show full text]
  • The Vacuolar H Atpase Α3 Subunit Negatively Regulates Migration And
    cells Article The Vacuolar H+ ATPase α3 Subunit Negatively Regulates Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cells Mette Flinck 1, Sofie Hagelund 1, Andrej Gorbatenko 2, Marc Severin 1, Elena Pedraz-Cuesta 1, Ivana Novak 1, Christian Stock 3 and Stine Falsig Pedersen 1,* 1 Section for Cell Biology and Physiology, Department of Biology, Faculty of Science, University of Copenhagen, DK-2100 Copenhagen, Denmark; mette.fl[email protected] (M.F.); [email protected] (S.H.); [email protected] (M.S.); [email protected] (E.P.-C.); [email protected] (I.N.) 2 Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; [email protected] 3 Department of Gastroentero-, Hepato- and Endocrinology, Hannover Medical School, D-30625 Hannover, Germany; [email protected] * Correspondence: [email protected] Received: 12 December 2019; Accepted: 13 February 2020; Published: 18 February 2020 Abstract: Increased metabolic acid production and upregulation of net acid extrusion render pH homeostasis profoundly dysregulated in many cancers. Plasma membrane activity of vacuolar H+ ATPases (V-ATPases) has been implicated in acid extrusion and invasiveness of some cancers, yet often on the basis of unspecific inhibitors. Serving as a membrane anchor directing V-ATPase localization, the a subunit of the V0 domain of the V-ATPase (ATP6V0a1-4) is particularly interesting in this regard. Here, we map the regulation and roles of ATP6V0a3 in migration, invasion, and growth in pancreatic ductal adenocarcinoma (PDAC) cells. a3 mRNA and protein levels were upregulated in PDAC cell lines compared to non-cancer pancreatic epithelial cells.
    [Show full text]
  • Systematic Analysis of Palatal Transcriptome to Identify Cleft Palate Genes Within Tgfβ3-Knockout Mice Alleles: RNA-Seq Analysis of Tgfβ3 Mice Ozturk Et Al
    Systematic analysis of palatal transcriptome to identify cleft palate genes within TGFβ3-knockout mice alleles: RNA-Seq analysis of TGFβ3 Mice Ozturk et al. Ozturk et al. BMC Genomics 2013, 14:113 http://www.biomedcentral.com/1471-2164/14/113 Ozturk et al. BMC Genomics 2013, 14:113 http://www.biomedcentral.com/1471-2164/14/113 RESEARCH ARTICLE Open Access Systematic analysis of palatal transcriptome to identify cleft palate genes within TGFβ3-knockout mice alleles: RNA-Seq analysis of TGFβ3 Mice Ferhat Ozturk1,4, You Li2, Xiujuan Zhu1, Chittibabu Guda2,3 and Ali Nawshad1* Abstract Background: In humans, cleft palate (CP) accounts for one of the largest number of birth defects with a complex genetic and environmental etiology. TGFβ3 has been established as an important regulator of palatal fusion in mice and it has been shown that TGFβ3-null mice exhibit CP without any other major deformities. However, the genes that regulate cellular decisions and molecular mechanisms maintained by the TGFβ3 pathway throughout palatogenesis are predominantly unexplored. Our objective in this study was to analyze global transcriptome changes within the palate during different gestational ages within TGFβ3 knockout mice to identify TGFβ3-associated genes previously unknown to be associated with the development of cleft palate. We used deep sequencing technology, RNA-Seq, to analyze the transcriptome of TGFβ3 knockout mice at crucial stages of palatogenesis, including palatal growth (E14.5), adhesion (E15.5), and fusion (E16.5). Results: The overall transcriptome analysis of TGFβ3 wildtype mice (C57BL/6) reveals that almost 6000 genes were upregulated during the transition from E14.5 to E15.5 and more than 2000 were downregulated from E15.5 to E16.5.
    [Show full text]
  • Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery
    fphar-07-00121 May 7, 2016 Time: 11:45 # 1 REVIEW published: 10 May 2016 doi: 10.3389/fphar.2016.00121 Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery Paola Imbrici1*, Antonella Liantonio1, Giulia M. Camerino1, Michela De Bellis1, Claudia Camerino2, Antonietta Mele1, Arcangela Giustino3, Sabata Pierno1, Annamaria De Luca1, Domenico Tricarico1, Jean-Francois Desaphy3 and Diana Conte1 1 Department of Pharmacy – Drug Sciences, University of Bari “Aldo Moro”, Bari, Italy, 2 Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Bari, Italy, 3 Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Bari, Italy In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation, and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, Edited by: disabling, or life-threatening. In spite of this, ion channels are the primary target of only Maria Cristina D’Adamo, University of Perugia, Italy about 5% of the marketed drugs suggesting their potential in drug discovery. The current Reviewed by: review summarizes the therapeutic management of the principal ion channelopathies Mirko Baruscotti, of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and University of Milano, Italy Adrien Moreau, pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion Institut Neuromyogene – École channels.
    [Show full text]
  • The Symptom Profile and Experience of Children with Rare Life-Limiting Conditions
    The symptom profile and experience of children with rare life-limiting conditions: Perspectives of their families and key health professionals Document Title The symptom profile and experience of children with rare life-limiting conditions: Perspectives of their families and key health professionals Authors Cari Malcolm, Sally Adams, Gillian Anderson, Faith Gibson, Richard Hain, Anthea Morley, Liz Forbat. Publisher Cancer Care Research Centre, University of Stirling Publication Date 2011 Target Audience Paediatric palliative care staff, paediatric clinicians, policy-makers, service developers, families supporting children with life-limiting conditions. Funded By Children’s Hospice Association Scotland Key Words Advance care planning, Batten disease, expertise, extended family, family, Morquio disease, progressive life-limiting, relationships, Sanfilippo disease, siblings, symptoms. Contact Details www.cancercare.stir.ac.uk Tel: 01786 849260 Email: [email protected] Copyright This publication is copyright CCRC and may be reproduced free of charge in any format or medium. Any material used must be fully acknowledged, and the title of the publication, authors and date of publication specified. The symptom profile and experience of children with rare life- limiting conditions: Perspectives of their families and key health professionals Executive Summary Background Many non-malignant life-limiting conditions are individually extremely rare and little is known, even by professionals in the field, about the actual day-to-day symptomatology or the impact of these symptoms on the child and family. With little recorded in the literature regarding the symptoms that children with rare life-limiting conditions experience, and the associated impact of managing these symptoms on the wider family, an opportunity exists to widen the knowledge base in this area.
    [Show full text]