Abstract
The tyrosine hydroxylase (TH) gene encodes a monoxygenase that catalyzes the rate limiting step in dopamine biosynthesis. A hallmark of Parkinson’s disease (PD) is the loss of dopaminergic neurons in the substantia nigra. Consistent with the essential role of TH in dopamine homeostasis, missense mutations in both alleles of TH have been associated with severe Parkinsonism-related phenotypes including infantile Parkinsonism. It has been speculated for a long time that genetic variants in the TH gene modify adult-onset PD susceptibility but the answer has not been clear. Genetic variants (both sequence variations and structural variations) can be classified into three categories based on their relative frequency in population: common variants (polymorphisms), rare variants and mutations. Each of these factors has a different mode in influencing the genetic risk and often requires different approaches to decipher their contributions to the disease. In the past few years, the revolutionary advances in genomic technology have allowed systematic evaluations of these genetic variants in PD, such as the genome-wide association study (GWAS, to survey common variants), copy number variation analysis (to detect structural variations), and massive parallel next generation sequencing (to detect rare variants and mutations). In this review, we have summarized the latest evidence on TH genetic variants in PD, including our ongoing effort of using whole exome sequencing to search for rare variants in PD patients.
Keywords: Rare variant, copy number variations, Parkinson’s disease, genetic association, tyrosine hydroxylase. polymorphism, next generation sequencing, genome wide association study.
CNS & Neurological Disorders - Drug Targets
Title:Tyrosine Hydroxylase Gene: Another Piece of the Genetic Puzzle of Parkinson’s Disease
Volume: 11 Issue: 4
Author(s): Guney Bademci, Jeffery M. Vance and Liyong Wang
Affiliation:
Keywords: Rare variant, copy number variations, Parkinson’s disease, genetic association, tyrosine hydroxylase. polymorphism, next generation sequencing, genome wide association study.
Abstract: The tyrosine hydroxylase (TH) gene encodes a monoxygenase that catalyzes the rate limiting step in dopamine biosynthesis. A hallmark of Parkinson’s disease (PD) is the loss of dopaminergic neurons in the substantia nigra. Consistent with the essential role of TH in dopamine homeostasis, missense mutations in both alleles of TH have been associated with severe Parkinsonism-related phenotypes including infantile Parkinsonism. It has been speculated for a long time that genetic variants in the TH gene modify adult-onset PD susceptibility but the answer has not been clear. Genetic variants (both sequence variations and structural variations) can be classified into three categories based on their relative frequency in population: common variants (polymorphisms), rare variants and mutations. Each of these factors has a different mode in influencing the genetic risk and often requires different approaches to decipher their contributions to the disease. In the past few years, the revolutionary advances in genomic technology have allowed systematic evaluations of these genetic variants in PD, such as the genome-wide association study (GWAS, to survey common variants), copy number variation analysis (to detect structural variations), and massive parallel next generation sequencing (to detect rare variants and mutations). In this review, we have summarized the latest evidence on TH genetic variants in PD, including our ongoing effort of using whole exome sequencing to search for rare variants in PD patients.
Export Options
About this article
Cite this article as:
Bademci Guney, M. Vance Jeffery and Wang Liyong, Tyrosine Hydroxylase Gene: Another Piece of the Genetic Puzzle of Parkinson’s Disease, CNS & Neurological Disorders - Drug Targets 2012; 11 (4) . https://dx.doi.org/10.2174/187152712800792866
DOI https://dx.doi.org/10.2174/187152712800792866 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Effects of the Novel Non-Peptidyl Low Molecular Weight Radical Scavenger IAC in Different Models of Inflammation: A New Perspective in Anti-Inflammatory Therapy
Current Medicinal Chemistry Synthesis and Preliminary Biological Evaluation of New Heterocyclic Carboxamide Models
Letters in Drug Design & Discovery Genetic and Molecular Factors in Drug-Induced Liver Injury: A Review
Current Drug Safety Drug-Loaded Nanocarriers in Tumor Targeted Drug Delivery
Current Biotechnology Interrelationships of Circulating Tumor Cells with Metastasis and Thrombosis: Role of MicroRNAs
Current Pharmaceutical Design Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma
Current Medicinal Chemistry Neonatal Fc Receptor and its Role in the Absorption, Distribution, Metabolism and Excretion of Immunoglobulin G-Based Biotherapeutics
Current Drug Metabolism Netrin and DCC: Axon Guidance Regulators at the Intersection of Nervous System Development and Cancer
Current Drug Targets Potential Applications of Induced Pluripotent Stem Cells (iPSCs) in the Modeling of Gastrointestinal Disorders
Current Stem Cell Research & Therapy An Antifungal Peptide with Antiproliferative Activity Toward Tumor Cells from Red Kidney Beans
Protein & Peptide Letters Probable Mechanisms Involved in Immunotoxin Mediated Capillary Leak Syndrome (CLS) and Recently Developed Countering Strategies
Current Molecular Medicine Pharmacokinetic and Toxicological Characteristics of Tripterigium Glycosides and Their Derivatives
Current Drug Metabolism Vitamin D and Cystic Fibrosis Lung Disease
Mini-Reviews in Medicinal Chemistry Pleiotropic Functions of Rho GTPase Signaling: A Trojan Horse or Achilles Heel for Breast Cancer Treatment?
Current Drug Targets Aldehyde Dehydrogenase as a Marker for Stem Cells
Current Stem Cell Research & Therapy Application of Decoy Oligodeoxynucleotides-Based Approach to Renal Diseases
Current Drug Targets Development and Tailoring of Hybrid Lipid Nanocarriers
Current Pharmaceutical Design Regulation of Protective and Pathogenic Th17 Responses
Current Immunology Reviews (Discontinued) Cell Biological Manifestations of Bisdioxopiperazines: Treatment of Human Tumor Cell Lines in Culture
Anti-Cancer Agents in Medicinal Chemistry Cancer and the Endogenous “Pineal Clock”: A Means of Early Diagnosis and Successful Treatment as Well as Prevention of Cancers
Current Aging Science