Genetic Disease Discovery and Therapeutics
- 1st Edition - October 22, 2024
- Author: Moyra Smith
- Language: English
- Paperback ISBN:9 7 8 - 0 - 4 4 3 - 2 3 6 4 8 - 8
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 2 3 6 4 7 - 1
Genetic Disease Discovery and Therapeutics presents information on the methods used to determine how specific gene defects influence pathology and phenotype and to review novel… Read more
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Request a sales quoteGenetic Disease Discovery and Therapeutics presents information on the methods used to determine how specific gene defects influence pathology and phenotype and to review novel therapeutic approaches designed for the treatment of specific genetic and genomic disorders.
This book investigates methodologies applied to the characterization of downstream functional effects of specific gene mutations associated with altered phenotypes and clinical disease. It documents evidence of how specific mutations influence pathology and lead to disease manifestations. This book also reviews information on therapeutic approaches that could potentially be applied in diseases due to gene defects. Genetic Disease Discovery and Therapeutics is a valuable reference for scientists and graduate students involved in laboratory research related to genetics, physiology, pathology, and pharmacology as well as clinicians who encounter patients with genetic disorders.
This book investigates methodologies applied to the characterization of downstream functional effects of specific gene mutations associated with altered phenotypes and clinical disease. It documents evidence of how specific mutations influence pathology and lead to disease manifestations. This book also reviews information on therapeutic approaches that could potentially be applied in diseases due to gene defects. Genetic Disease Discovery and Therapeutics is a valuable reference for scientists and graduate students involved in laboratory research related to genetics, physiology, pathology, and pharmacology as well as clinicians who encounter patients with genetic disorders.
• Considers refined diagnostic techniques for genetic diseases.
• Documents evidence regarding mechanisms through which gene defects alter biochemical function and lead to pathology.
• Presents new techniques being applied to the treatment of gene and genome-based disorders.
• Aims to consider the goals of personalized precision medicine as defined by the NIH.
• Documents evidence regarding mechanisms through which gene defects alter biochemical function and lead to pathology.
• Presents new techniques being applied to the treatment of gene and genome-based disorders.
• Aims to consider the goals of personalized precision medicine as defined by the NIH.
Scientists and graduate students, involved in laboratory research related to genetics, physiology, pathology, pharmacology, Clinicians who encounter patients with genetic disorders, which may include General Practitioners, Pediatricians, Internists, Obstetrician Gynecologists, Genetic Counsellors
- Title of Book
- Cover image
- Title page
- Table of Contents
- Copyright
- Dedication
- Epigraph
- Preface
- Acknowledgments
- Section I. Disease classification and possible diagnosis
- Chapter 1. Clinical features to consider in a patient with possible genetic disease
- Clinical genetics assessment: History and physical examination
- Family history information
- Resources of information relevant to developmental defects and genetic disorders
- Databases with information on developmental defects and genetic diseases
- Aspects of developmental delay
- Movement disorders and cerebral palsy
- Autism
- Example of clinical care in a patient with a chromosomal disorder: Angelman syndrome
- Access to clinical genetic services
- WHO report on recommendations for community genetic services in low and middle income countries (2010)
- Genetic contributions to the pathogenesis of congenital heart disease
- Emerging techniques
- Chromosome aneuploidies associated with congenital heart disease
- Congenital heart disease in specific chromosome aneuploidies
- Williams syndrome
- Jacobsen syndrome
- Chromosome 1p36.3 deletion syndrome
- Deletion of chromosome 1q21.1
- Holt Oram syndrome
- Noonan syndrome
- Coffin Siris syndrome
- Smith-Lemli-Opitz syndrome
- Congenital heart disease therapeutic approaches
- Tetralogy of Fallot
- Congenital heart disease in specific syndromic disorders
- Specific clinical management of heart disease in patients with Noonan syndrome
- Neural tube defects, gene–environment interactions
- Breakthrough in understanding etiology of neural tube defects
- Neural tube closing mechanisms
- Studies on genes in the folate metabolism pathway
- Gene environment interactions in neural tube defects
- Folate deficiency and methylation
- One carbon metabolism and folate
- Mitochondrial one carbon metabolism
- Global efforts to implement folate fortification of foods
- Burden of neural tube defects in Africa
- Surgical repair of neural tube defects
- Chapter 2. Determining the presence of altered values in clinical laboratory studies
- Acutely ill patients in the newborn nursery or patients with possible metabolic disease
- Patients with dysmorphology
- Patients with abnormal clinical chemistry results
- Disorders of the urea cycle
- Organic acidemias, organic acidurias
- Clinical utility of genome sequencing
- Exome sequencing and diagnostic value in inborn errors of metabolism
- Next-generation metabolic screening in diagnosis
- Reanalysis of sequence data
- Cornelia de Lange syndrome
- Clinical management
- Structural genes with defects that may occur
- Regulatory genes
- Genes with chromatin associated functions
- Genes with other functions that may be involved SMC1A, SMC3, involved DNA repair
- Chapter 3. Further laboratory-based investigations for possible gene- or genome-based disorders
- Investigations in possible gene or genome-based disorders
- Patient evaluation
- Cytogenetic studies
- Newer approaches to chromosome studies to detect structural chromosome abnormalities
- Optical gene mapping
- Use of long read sequencing in identification of structural chromosome abnormalities
- Genomic defects associated with developmental defects
- Clinical utility of genome sequencing
- Early recognition of malformation syndromes
- Syndromic disorders
- Inborn errors of metabolism
- Next-generation metabolomic screening
- Newborn screening programs
- Primary conditions screened for in California newborn screening program 2022
- Secondary condition screened for include in California include the following
- Genome sequencing in newborn screening
- Rapid genome sequencing in critically ill infants and children
- Sequencing studies on different populations
- Pan-genomic reference sequence
- Genomic landscape of rare diseases in the Middle-East
- Importance of metabolomic and DNA sequencing analyses in diagnoses of causes of intellectual disability
- Diagnostic testing
- Recommendation for clinical genetic and metabolomic investigations in intellectual disability
- Expanding newborn screening programs
- Variants in the nonprotein coding genome
- Exome sequencing and diagnostic value
- Epigenetic changes
- Next-generation metabolic screening in diagnosis
- Autism
- Fragile X syndrome
- Molecular diagnosis of fragile X syndrome
- Diagnostic DNA sequence analyses, problems, and consideration
- Clinical interpretation of sequence variants
- Polygenic risk score analyses in complex common diseases
- Somatic mutations
- Section II. Application of therapies and strategies for development of therapies
- Chapter 4. Review possible therapies to address clinical manifestations including symptoms and signs and abnormal results of metabolic, biochemical, gene-based studies
- Mitochondrial functions and dysfunctions in mitochondrial disorders
- Mitochondrial DNA
- Mitochondrial haplotypes
- Proteins within mitochondria
- Mitochondrial dynamics
- Mitofusin 2 dysfunctions
- Progress in treatment of mitochondrial diseases
- Pathology and tissue analyses
- Mitochondrial disease with particular focus on adults and neurological manifestation
- Mitochondrial depletion syndrome
- Friedreich ataxia
- Treatment and prevention of mitochondrial disease
- Small molecule therapies designed to increase mitochondrial function
- Peroxisomes and genetic disorders involving peroxisomes
- Peroxisome discovery
- Peroxisomal biogenesis disorders
- Refsum disease
- Rhizomelic chondrodysplasia punctata new information
- Generation of stem cell including hematopoietic stem cells for therapy
- Mesenchymal stem cells
- Genetically determined erythroid defects
- Blackfan-Diamond anemia
- Fanconi anemia
- Hereditary anemias due to genetic errors that impact the glycolytic pathway
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Lysosome membrane transporters
- Lysosomal diseases of ion transport
- CLCN7
- Disorders due to defective export from lysosomes
- Solute carriers active at other location
- Glycogen storage diseases
- Glycogen storage diseases, genes, protein functions, organ involvement
- Disease Gene Protein function Organ involved.
- Neurological manifestation and glycogen metabolic defects
- Ion channel–Associated disorders
- CACNA1C channelopathies
- CACNA1B
- Calcium ion channel variants associated with trigeminal neuralgia
- Ion channels in glomerular function
- Chapter 5. Review of investigations and possible therapies to address underlying disease manifestations
- Inherited disorders of vitamin metabolism
- Folic acid (vitamin b9) and the folic acid receptor
- Folate transport and metabolism
- Biotin
- Vitamin D hydroxylation deficient ricketts
- Vitamin K
- Therapeutic development in specific germline genetic diseases
- Range of therapeutic options in lysosomal storage diseases
- Hematopoietic stem cell transplantation
- Small molecule therapies
- Enzyme replacement therapies
- Gene therapy
- Therapies for neuropathic lysosomal storage diseases
- Gene editing lysosomal storage diseases
- Lysosomal diseases with abnormal storage of mucopolysaccharides and advances in therapy
- Description of diseases and response to therapies
- Hunter syndrome
- MPS IV Morquio syndrome
- Mucopolysaccharidosis type 3 Sanfilippo disease
- Lysosomal storage diseases associated with abnormal storage of gangliosides, sphingolipids, and/or ceramides
- Pompe disease
- Creatine metabolism and brain creatine deficiency
- Adrenoleukodystrophy
- Monoamine neurotransmitter disorders and approaches to therapy
- Gene defects in monoamine neurotransmitter disorders
- Dopamine Receptor
- Endocrine disorders
- Thyroid related disorders
- Congenital hypothyroidism
- Pendred syndrome
- Congenital adrenal hyperplasia
- Porphyria
- Processes involved in the degradation of heme
- Porphyrin and porphyria
- Chapter 6. Functional impairments, known genetic disorders, and review reports of established and possible therapies for specific genetic diseases
- Ciliopathies
- Genes Functions
- Joubert syndrome and Meckel syndrome
- Neuronal primary cilia and metabolism
- Pancreatic cells and primary cilia
- Polycystic kidney disease
- Voltage-gated channels and renal dysfunction
- Bartter syndrome
- Gitelman syndrome
- Monogenic kidney disease
- Inborn errors of immunity
- Antibody history
- Specific immune disorders
- Newborn screening for inborn errors of immunity
- Severe combined immunodeficiency
- Defects in B cell development and gamma globulin defects
- Types of agammaglobilinemia
- Systemic lupus erythematosus
- Genetic defects leading to complement dysregulation
- Additional inborn errors associated with impaired immunity
- Wiskott–Aldrich syndrome
- Fanconi Anemia
- Alpha-1-antitrypsin deficiency
- Treatment for alpha-1-antitrypsin deficiency
- RNA interference therapy in alpha-1-antitrypsinsin liver disease
- Achondroplasia
- Natriuretic peptide system in growth
- Osteogenesis imperfecta
- Treatment of osteogenesis imperfecta
- Hypophosphatasia
- Hypophosphatasia and hypophosphatemic rickets
- X-linked hypophosphatemia phenotypic manifestations
- Cystic fibrosis
- Early reports
- Cystic fibrosis gene mapping and gene product identification
- Defining classes of cystic fibrosis gene defects
- CFTR modulators in therapy
- Glycogen storage diseases
- Glycosylation
- Biometals
- Specific forms of XPA, chromosome location, impacted gene
- Defects in DNA repair processes
- Fanconi Anemia
- Ataxia telangiectasia
- Hearing and deafness
- Peripheral and central auditory circuits
- Defining parameters of hearing and deafness
- Waardenburg syndrome
- Section III. Discussion of specific diseases where gene therapy, gene-based therapies or small molecule-based therapies have been successful
- Chapter 7. Examples of diseases where appropriate therapies were discovered
- Epilepsies: Genetic testing and relevance to treatment
- Splicing factors and poison exons
- Systemic analysis and reanalysis of exome sequencing data in epilepsy
- Treatment of epilepsies
- Possibilities for precision medicine in epilepsies
- Absence epilepsy
- Genome wide study epilepsy key genes
- Ion channel associated disorders
- Introduction
- CACNA1C channelopathies
- CACNA1B
- CACNA1D
- Calcium ion channel variants associated with trigeminal neuralgia
- Therapeutic approaches to Duchenne Muscular Dystrophy (DMD)
- Hemoglobinopathies sickle cell disease, thalassemia advances in treatment
- Treatment of sickle cell disease and beta thalassemia
- Hematopoietic stem cells
- Gene correction of the sickle cell disease mutation
- FDA approved gene therapies for hemoglobinopathies
- Gene editing relevant for sickle cell disease and beta thalassemia
- Preparation for transplantation of hematopoietic stem cells
- Comparing treatment strategies for sickle cell disease
- Efficiency of gene therapy for beta thalassemia
- Alpha thalassemia major
- Spinal muscular atrophy
- Advances in treatment of hemophilia due to factor VIII deficiency
- Gene therapy for Hemophilia A due to factor VIII deficiency
- Diseases where limited progress has been made on development of molecular based therapies
- Rett syndrome and progress toward development of therapy
- MECP2 duplication syndrome Rett syndrome
- Cell signaling pathway to TSC and MTOR
- Tuberous sclerosis, the MTOR pathways, autism, and impaired neurological functions
- Protein folding, protein unfolding and formation of aggregates
- Unfolded protein response
- Unfolded proteins and aggregate formation
- Aggregates in neurodegenerative diseases
- Chapter 8. Therapies that address altered gene regulation
- Examples of disorders due to altered transcription factor activity
- ZIC2 mutations
- FOXP3 transcription factor
- Disorders due to defects in mRNA translation
- Craniosynostosis
- Disorders of metal metabolism
- Wilson disease
- Treatment of Wilson disease
- Menkes disease
- Therapies to impact posttranscriptional gene expression
- Transthyretin amyloidosis
- Acute intermittent porphyria
- Hyperlipidemias
- PCSK9 and hyperlipidemia
- Angelman syndrome
- Malformation syndromes due to regulatory gene defects
- Clinical findings in specific epigenetic disorders
- Epigenetics, chromatin disorders, and clinical medicine
- Examples of genes encoding factor involved in epigenetic modifications
- Translation of mRNA to protein
- Translation defects and ribosome pathologies
- Regulatory genome defects identified in whole genome sequencing
- Long non-protein-coding RNAs
- Mitochondria, RNA and protein synthesis
- IPEX syndrome transcription factor FOXP3 defect
- Transcription regulation
- Nail patella syndrome and LMX1B transcription factor
- HOX transcription factors
- Chapter 9. Defining disease mechanisms, designing therapies and roles of stem cells
- Urea cycle disorders
- Familial hypercholesterolemia and dyslipidemia
- Lipid transport
- Classification of lipoprotein disorders
- Advances in treatment of hypercholesterolemia
- PCSK9
- APO B
- Apolipoprotein B100
- Hypertriglyceridemia
- Genetics of common complex coronary disease
- Stem cells and cell therapies
- CD34
- Muse cell discovery
- Muse cells and epidermolysis bullosa
- Pluripotent stem cells
- Pluripotent stem cells and gene therapy
- Stem cell therapies
- Crispr-Cas9 gene editing in pluripotent stem cells
- Cell-based gene therapies
- Hematopoietic stem cell–based therapies
- Liver cell therapy
- Cell-based therapies in visual diseases
- Section IV. Review research on therapeutic design
- Chapter 10. Review research designed to investigate gene function and possible impact of specific variants
- Huntington disease
- Huntington disease identification of disease modifiers
- Modifiers of the phenotype in Huntington's disease
- Duchenne Muscular dystrophy in animal models
- Duchenne Muscular dystrophy in humans
- Key components included in microdystrophins
- Charcot Marie Tooth disease
- Limb girdle muscular dystrophy
- Treacher Collins syndrome (TCS)
- Ribosome biogenesis and ribosomopathies
- Ribosomopathies
- Vision and hearing: The visual cycle, retina and retinitis pigmentosa
- Retinal pigment epithelium
- Visual pigments
- Treatment investigations in Usher syndrome
- Gene therapy in defects involving retinal pigment epithelium and photoreceptor defects
- Retinitis pigmentosa
- Usher syndrome and autosomal recessive retinitis pigmentosa
- Retinitis pigmentosa (RP) gene mapping
- Stargardt disease
- The retina and age related macular degeneration
- Phenotypes of macular degeneration
- Pathology in macular degeneration
- Age related neurodegenerative conditions
- Autophagy and neurodegenerative conditions
- Organized from highest to lowest prevalence
- Amyotrophic lateral sclerosis
- Amyotrophic lateral sclerosis single gene mutations and variants identified in special genome-wide association studies
- Parkinson's disease
- Treatment of Parkinson disease
- APOE4 genetic variant and Alzheimer research
- Underlying pathological features of neurodegenerative diseases
- Approaches to treatment of Alzheimer disease
- Chapter 11. Designing therapies relevant in human genetic disorders
- Section A: Designing therapies for specific diseases
- Inborn errors of metabolism: Liver transplantation
- Age at transplantation
- Delivery of therapeutic across the blood–brain barrier
- Rare diseases, precision medicines, and orphan drug designations
- Designing RNA-based therapies
- MicroRNAs
- RNA-based therapies
- Long noncoding RNAs and microRNAs and gene expression
- RNA splicing, splicing as regulator, splicing defects, genetic diseases therapies
- PreRNA splicing mutation in lysosomal storage diseases
- Small molecule correction of splicing defect in familial dysautonomia
- Therapy of mutations that lead to impaired synthesis of dopamine and serotonin
- Antisense oligonucleotide therapy
- Gene editing
- Crispr CAS9 gene editing
- Additional approaches to gene editing
- Considering editing of Fanconi anemia mutations and their editing in primary cells from patients
- Precision gene editing in the eye
- Congenital disorders in the Ras signaling pathway and approaches to therapy
- Gene defects in Noonan syndrome–Noonan-like syndrome (NS), defects in RAS signaling pathway
- Neurodegenerative conditions and specific physiologic processes involved
- Amyotrophic lateral sclerosis
- Emerging therapies in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
- Further research and development of therapeutics for genetic diseases
- Identification of small molecules for treatment of genetic diseases
- The orphan Drug Act
- Computerized drug design
- Chemoinformatics
- Clinical trial designs for rare diseases
- Report of treatment of a rare genetic disease in multinational trials
- Quest for therapies for myotonic dystrophy
- Additional treatments for refractory hypercholesterolemia
- Genetic diseases of muscle where gene defects and disease mechanism are known, and where molecular-based therapies are in development
- Therapies for CMT
- Limb-girdle muscular dystrophy
- Toward therapy of limb-girdle muscular dystrophies
- Section B: Pharmacogenetics pharmacogenomics
- Genes with variants that most commonly impact the activities of therapeutic agents
- Cytochrome P450 family
- Clinical implementation of pharmacogenetic testing PGx
- Clinical pharmacogenomics implementation consortium CPIC
- Pharmacogenomic analysis methods by gene panel
- HLA variants relevant to pharmacogenomics
- Hypersensitivity reactions
- Population specific pharmacogenetics
- Pharmacogenetics in anesthesia
- Metronidazole sensitivity
- Section V. Clinical trials design and permissions
- Chapter 12. Clinical trial designs and permissions
- Human subjects research
- FDA guidance of clinical trials
- Informed consent
- Clinical trials for achondroplasia
- Advances in the treatment of inborn errors of metabolism
- X-linked myotubular myopathy
- Bioinformatics and cheminformatics in discovery of new medications
- Information on specific clinical trials and trial endpoints
- Two-step gene editing
- Gene therapy vectors and unexpected problems
- Aspects of cost
- CAR T-cell therapy in auto-immune diseases
- Gaucher disease treatment and cost
- Monoclonalantibodies as therapeutic agents
- Monoclonal antibodies in the treatment of monogenic disorders
- Target discovery through genetic studies and development of therapies
- Treatment through suppression of gene function
- Treatment through inhibiting gene product
- Index
- No. of pages: 454
- Language: English
- Edition: 1
- Published: October 22, 2024
- Imprint: Academic Press
- Paperback ISBN: 9780443236488
- eBook ISBN: 9780443236471
MS
Moyra Smith
Dr. Moyra Smith is a Professor Emerita in the Department of Pediatrics and Human Genetics, College of Health Sciences, at the University of California, Irvine, and in past years has held appointments at the National Institutes of Health and Johns Hopkins University. In 2017, the UCI Emeriti Association awarded Dr. Smith the UCI Outstanding Emerita Award in recognition of her continuing research on genetics and genomics, strong record of publications, active engagement with programs in the Department of Pediatrics, mentoring of graduate students, and involvement with the CART Autism Center at UCI. Dr. Moyra Smith has published more than 100 scientific articles in peer-reviewed journals such as Frontiers in Molecular Biosciences, Molecular Psychiatry, the Journal of Medical Genetics (JMG), and Cytogenetics Cell Genetics.
Affiliations and expertise
Professor Emerita, Department of Pediatrics and Human Genetics, College of Health Sciences, University of California, Irvine, CA, USARead Genetic Disease Discovery and Therapeutics on ScienceDirect