Medical Genetics - V. M. Zaporozhan 2005



Preface

Introduction to Medical Genetics

Subject and Tasks of Medical Genetics. History of Medical Genetics

Subject and Tasks of Medical Genetics

Main Milestones in the History of Medical Genetics

Molecular Basis of Heredity

Structure and Functions of DNA

Structure and Functions of RNA

Gene

Structure of the Eukaryotic Gene

The Genetic Code and Its Properties

Gene Expression

Regulation of Gene Expression

Mitochondrial DNA

Molecular Foundations of Heredity

Human Genome

Cytological Foundations of Heredity

Cellular Structures as Bearers of Genetic Information

Structure and Functions of the Nucleus and Chromosomes - Structure of the Nucleus

Structure and Functions of the Nucleus and Chromosomes - Functions of the Nucleus

Structure and Functions of the Nucleus and Chromosomes - Chemical Composition of Chromosomes

Structure and Functions of the Nucleus and Chromosomes - Chromosome Structure

Structure and Functions of the Nucleus and Chromosomes — Telomeres and Telomerase

Human Karyotype

Genetic Maps of Human Chromosomes

Review Questions for Chapter 1

Etiology of Hereditary Diseases

Classification of Mutations

Spontaneous and Induced Mutations

Somatic and Germline Mutations

Gene Mutations

Classification of Gene Mutations

Types of Stable Mutations

Dynamic Mutations (Trinucleotide Repeat Expansions)

Phenotypic effect of gene mutations. Genetic and cellular polymorphism of monogenic disorders

Frequency of Gene Mutations

Types of mutations caused by changes in chromosome number and structure

Chromosomal aberrations

Types of Mutations Caused by Changes in Chromosome Number and Structure

Genomic Mutations - Polyploidy

Types of mutations caused by changes in the number and structure of chromosomes

Genomic mutations - Heteroploidy (aneuploidy)

Types of Mutations Caused by Changes in Chromosome Number and Structure

Mosaicism and Chimerism (Mixoploidy)

Recording Normal and Altered Human Karyotypes

Mutagenic Factors

Physical Mutagens

Chemical Mutagens

Biological Mutagens

Defense Mechanisms Reducing the Mutation Rate in Humans

Non-Mendelian Inheritance in Humans

Genomic Imprinting

Sex Chromatin (Barr Bodies)

Uniparental Diploidy, Uniparental Disomy, and Isodisomy

Trinucleotide Repeat Expansion

Gonadal Mosaicism

Mitochondrial Inheritance

Review Questions for Chapter 2

Classification, general characteristics, and symptomatology of hereditary diseases. General clinical diagnostics.

Classification and general characteristics of hereditary diseases

Classification, general characteristics, and symptoms of hereditary diseases. General clinical diagnostics

Syndromological diagnosis in clinical genetics

Classification, general characteristics, and symptomatology of hereditary diseases. General clinical diagnostics

General principles of clinical diagnostics of hereditary diseases

Classification, general characteristics, and symptomatology of hereditary diseases. General clinical diagnostics.

Peculiarities of anamnesis collection

General principles of clinical diagnosis of hereditary diseases

Congenital malformations and microanomalies of development as signs of dysmorphogenesis

Classification, general characteristics, and symptomatology of hereditary diseases. General clinical diagnostics

General principles of clinical diagnostics of hereditary diseases

Description of the phenotype of a patient with hereditary pathology. Main micro-anomalies and developmental malformations

Symptoms of hereditary and congenital pathology across various age periods

Review questions for Section 3

Clinical-Genealogical Method

Significance of the Method. Principles of Pedigree Construction

Collection of Genealogical Anamnesis

Rules for Pedigree Construction

Genealogical Analysis and Genetic Risk Calculation

Clinical-genealogical method

Characteristics of pedigrees with various inheritance patterns

Autosomal dominant inheritance pattern

Clinical-Genealogical Method

Characteristics of Pedigrees with Various Inheritance Patterns

Autosomal Recessive Inheritance

Sex-Linked Inheritance

Pedigrees in Mitochondrial Inheritance

Clinical-genealogical method

Review questions for Chapter 4

Chromosomal Diseases

History of Human Cytogenetics

The Role of Chromosomal and Genomic Mutations in Ontogenesis

Classification of Chromosomal Diseases

Pathogenesis of Chromosomal Diseases

General Symptoms of Chromosomal Diseases

Clinical and cytogenetic characteristics of the most common chromosomal disorders and syndromes

The Concept of Microcytogenetic Syndromes

Diagnosis of Chromosomal Diseases

Chromosomal Disorders

Prenatal Diagnosis of Chromosomal Abnormalities

Principles of Medical-Genetic Counseling

Chromosomal Diseases

Review questions for Chapter 5

Monogenic Disorders

Etiology of Monogenic Disorders

Genetic Heterogeneity of Monogenic Diseases

Clinical features of monogenic diseases

Classification of Monogenic Disorders

V. McKusick's Catalog of Genes and Mendelian Inheritance

Population frequency of monogenic diseases

Clinical Features and Genetics of Certain Monogenic Disorders

Autosomal Dominant Disorders

Clinical Features and Genetics of Selected Monogenic Disorders

Autosomal Recessive Disorders

Clinical Features and Genetics of Certain Monogenic Disorders

Sex-Linked Inheritance

Sex-Linked Inheritance – X-Linked Recessive Disorders

Sex-Linked Inheritance - X-Linked Dominant Disorders

Sex-Linked Inheritance - Y-Chromosome-Linked Inheritance

Mitochondrial Diseases

Diagnosis of Monogenic Disorders

Prenatal Diagnosis of Monogenic Disorders

Genetic Counseling

Monogenic Diseases

Principles of Treatment for Monogenic Disorders

Monogenic Disorders

Review Questions for Chapter 6

Multifactorial Diseases

General Characteristics and Classification

Determination of Genetic Risk

Genetics of Certain Common Multifactorial Diseases

Coronary Heart Disease

Essential Hypertension

Genetics of Certain Common Multifactorial Disorders

Thrombophilia

Genetics of Certain Common Multifactorial Diseases

Diabetes Mellitus

Chronic Pancreatitis

Genetics of Some Common Multifactorial Diseases

Bronchial Asthma

Epilepsy

Schizophrenia

Susceptibility to infectious diseases

Determination of Genetic Predisposition

Ecogenetics

Subject Matter of Ecogenetics

Examples of ecogenetic pathological reactions — α1-antitrypsin deficiency

Examples of Ecogenetic Pathological Reactions — Paraoxonase Enzyme Polymorphism

Examples of ecogenetic pathological reactions — Ecogenetic pathological reactions in carriers of cystinosis and Fanconi anemia genes

Examples of ecogenetic pathological reactions — Polymorphism of carcinogen metabolism genes

Examples of ecogenetic pathological reactions - Ecogenetic reactions to food products

Pharmacogenetics

What is pharmacogenetics? Phases of biotransformation

Examples of pharmacogenetic reactions - Erythrocyte hemolysis associated with glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency in red blood cells

Examples of Pharmacogenetic Reactions — Hypersensitivity to Dithylin

Examples of pharmacogenetic reactions – Malignant hyperthermia

Changes in Drug Responses in Patients with Hereditary Diseases

Review Questions for Chapter 7

Fundamentals of Oncogenetics

Genetics and Oncological Diseases

Regulation of the Mitotic Cycle

General characteristics of genes responsible for tumor development

Basics of Oncogenetics

Targets of Gene Action Involved in Carcinogenesis

Viral Oncogenes

Proto-oncogenes

Fundamentals of Oncogenetics

Tumor Suppressors

Basics of Oncogenetics

Mutator Genes

Fundamentals of Oncogenetics

Carcinogenic Factors

Basics of Oncogenetics

Potential for Molecular Genetic Diagnosis of Tumors

Fundamentals of Oncogenetics

Review Questions for Chapter 8

Congenital Malformations

Congenital malformations: general concepts, population frequency, and specific weight in the structure of morbidity and mortality

Classification of Congenital Malformations

Gene families responsible for hereditary developmental defects. Developmental genetics

Malformations associated with the action of teratogenic factors

The Concept of "Major" and "Minor" (Systemic) Teratogenesis

Principles of prenatal diagnosis of congenital malformations

Genetic Counseling for Congenital Malformations

Review Questions for Chapter 9

Diagnostic Methods for Hereditary Diseases

Methods for Diagnosing Hereditary Diseases

Syndromological Analysis

Diagnostic methods for hereditary diseases

Use of computer diagnostic software and databases

Methods of Diagnosing Hereditary Diseases

Cytogenetic Methods

Methods for Diagnosing Hereditary Diseases

Indications for Cytogenetic Diagnosis

Diagnostic Methods for Hereditary Diseases

Karyotyping Method

Methods for Diagnosing Hereditary Diseases

Molecular-Cytogenetic Methods

Methods of diagnosing hereditary diseases

Cytogenetic methods

Efficacy of cytogenetic methods

Diagnostic Methods for Hereditary Diseases

Cytogenetic Methods

Determination of Sex Chromatin

Methods for Diagnosing Hereditary Diseases

Molecular-Genetic Methods (DNA Diagnostic Methods)

Indications for DNA Diagnostics

Diagnostic Methods for Hereditary Diseases

Molecular Genetic Methods (DNA Diagnostics)

Starting Material for DNA Diagnostics

Diagnostic Methods for Hereditary Disorders

Stages of DNA Diagnostics Using the Polymerase Chain Reaction

Methods for Diagnosing Hereditary Diseases

Molecular Genetic Methods (DNA Diagnostic Methods)

Modification of PCR

Molecular-Genetic Methods (DNA Diagnostic Methods)

Other DNA Diagnostic Methods — Use of Restriction Endonucleases

Diagnostic Methods for Hereditary Diseases

Molecular Genetic Methods (DNA Diagnostics Methods)

Other DNA Diagnostic Methods — Electrophoresis of DNA Fragments

Methods of Diagnosing Hereditary Diseases

Molecular-Genetic Methods (DNA Diagnostic Methods)

Other DNA Diagnostic Methods — Southern Blot Hybridization

Methods for Diagnosing Hereditary Diseases

Other DNA Diagnostic Methods — DNA Sequencing

Methods of Diagnostics of Hereditary Diseases

Molecular Genetic Methods (DNA Diagnostics Methods)

Direct and Indirect Methods of DNA Diagnostics

Methods of Diagnosing Hereditary Diseases

DNA Microarrays

Diagnostic Methods for Hereditary Diseases

Molecular Genetic Methods (DNA Diagnostic Methods)

Application of Molecular Genetic Methods in Forensic Medicine for Personal Identification and Paternity/Kinship Testing

Diagnostic methods for hereditary disorders

Dermatoglyphic method

Methods for Diagnosing Hereditary Diseases

Biochemical Methods

Methods of Diagnosing Hereditary Diseases

Review Questions for Chapter 10

Prevention of Hereditary Diseases

Medical and social aspects of hereditary and congenital pathology in human populations

Types of Prevention of Hereditary Pathology

Population Genetic Monitoring

Medical-Genetic Counseling

Concept of Medical-Genetic Counseling

Medical Genetic Counseling

Organization of Medical Genetic Care for the Population of Ukraine

Objectives and Stages of Medical Genetic Counseling

Preconception Prevention of Hereditary Diseases and Congenital Malformations

Prenatal Diagnosis of Hereditary Diseases and Congenital Malformations

Classification of Prenatal Diagnostic Methods

Non-Invasive Methods - Maternal Serum Markers

Non-invasive methods — Ultrasound scanning

Non-invasive methods - Comprehensive screening program for prenatal diagnosis of congenital malformations and chromosomal syndromes. Prenatal screening

Invasive Methods

Prevention of Hereditary Disorders

Use of Fetal Cells Circulating in Maternal Blood for Prenatal Diagnosis of Hereditary Diseases

Prevention of Hereditary Diseases

Diagnostic Methods for Hereditary Pathology within Modern Reproductive Technologies Systems

Preimplantation Genetic Diagnosis

Diagnostic Methods for Hereditary Pathology in the System of Modern Reproductive Technologies

Genetic Testing of Sperm Donors Used for Artificial Insemination

Elimination of embryos and fetuses with hereditary pathology and congenital malformations

Prenatal Treatment of Certain Hereditary Diseases and Malformations

Mass Newborn Screening

Identification of heterozygous carriers of recessive mutant genes as a method of primary prevention

Identification of genes associated with late-onset hereditary diseases and predisposition genes for multifactorial disorders, alongside the prevention of such pathologies in gene carriers

Genetic Passport

Ethical, Moral, and Legal Issues in Medical Genetics

Review Questions for Chapter 11

Answers to self-assessment questions

History of Genetics

Genetic map of human chromosomes

Genetic Map of Reproductive Health (V. S. Baranov, 2004)

Glossary of Genetic Terms

References