Medical Genetics

Medical genetics is a medical specialty that applies the principles of genetics and genomics to the diagnosis, management, and prevention of human disease. This field investigates the role of single genes, chromosomes, and complex genomic variations in both rare hereditary disorders, such as cystic fibrosis and Huntington's disease, and common multifactorial conditions like heart disease and cancer. Its clinical practice involves a wide range of activities, including diagnostic and predictive genetic testing, prenatal screening, pharmacogenomics to tailor drug treatments, and providing crucial genetic counseling to help individuals and families understand and adapt to the medical, psychological, and familial implications of genetic contributions to health.

1. Fundamentals of Human Genetics and Genomics
   1. The Human Genome
      1. Structure of DNA and RNA
         1. Chemical Composition of DNA
            1. Nucleotide Components
            2. Phosphodiester Bonds
            3. Major and Minor Grooves
         2. Double Helix Structure
            1. Watson-Crick Model
            2. Antiparallel Strands
            3. Helical Parameters
         3. Base Pairing Rules
            1. Complementary Base Pairs
            2. Hydrogen Bonding Patterns
            3. Chargaff's Rules
         4. DNA vs. RNA Structure
            1. Sugar Differences
            2. Base Differences
            3. Single vs. Double Strand
         5. Types of RNA
            1. Messenger RNA (mRNA)
            2. Transfer RNA (tRNA)
            3. Ribosomal RNA (rRNA)
            4. MicroRNA (miRNA)
            5. Long Non-coding RNA (lncRNA)
            6. Small Interfering RNA (siRNA)
      2. Gene Structure and Function
         1. Definition of a Gene
            1. Classical Definition
            2. Modern Molecular Definition
            3. Functional Gene Units
         2. Exons and Introns
            1. Coding Sequences
            2. Non-coding Sequences
            3. Splice Sites
            4. Alternative Exons
         3. Promoters and Regulatory Elements
            1. Core Promoter Elements
            2. Proximal Promoter Elements
            3. Distal Regulatory Elements
            4. TATA Box
            5. CpG Islands
         4. Open Reading Frames
            1. Start Codons
            2. Stop Codons
            3. Reading Frame Shifts
         5. Pseudogenes
            1. Processed Pseudogenes
            2. Non-processed Pseudogenes
            3. Functional Significance
         6. Gene Families and Clusters
            1. Tandem Gene Clusters
            2. Dispersed Gene Families
            3. Orthologous and Paralogous Genes
      3. Chromosomes and Chromatin Organization
         1. Chromosome Anatomy
            1. Centromere Structure
            2. Telomere Structure
            3. Short Arm (p)
            4. Long Arm (q)
         2. Euchromatin vs. Heterochromatin
            1. Transcriptionally Active Regions
            2. Transcriptionally Inactive Regions
            3. Constitutive Heterochromatin
            4. Facultative Heterochromatin
         3. Nucleosome Structure
            1. Histone Octamer
            2. DNA Wrapping
            3. Linker DNA
            4. Histone H1
         4. Higher-Order Chromatin Structure
            1. 30-nm Fiber
            2. Loop Domains
            3. Condensed Metaphase Chromosomes
         5. Chromosome Territories in the Nucleus
            1. Nuclear Organization
            2. Chromosome Positioning
            3. Nuclear Compartments
      4. The Human Karyotype
         1. Chromosome Number and Classification
            1. Diploid Number (2n=46)
            2. Haploid Number (n=23)
            3. Chromosome Size Classification
         2. Sex Chromosomes vs. Autosomes
            1. X Chromosome
            2. Y Chromosome
            3. Autosomal Chromosomes (1-22)
         3. Karyotype Preparation and Analysis
            1. Cell Culture Methods
            2. Metaphase Arrest
            3. Chromosome Spreading
            4. Microscopic Analysis
         4. Chromosomal Banding Patterns
            1. G-banding Patterns
            2. Chromosome Ideograms
            3. Band Nomenclature
   2. Core Molecular Processes
      1. DNA Replication
         1. Enzymes Involved
            1. DNA Polymerases
            2. DNA Helicase
            3. DNA Ligase
            4. DNA Primase
            5. Single-Strand Binding Proteins
         2. Leading and Lagging Strand Synthesis
            1. Continuous Synthesis
            2. Discontinuous Synthesis
            3. Okazaki Fragments
         3. Replication Origins
            1. Origin Recognition Complex
            2. Replication Initiation
            3. Bidirectional Replication
         4. Proofreading and Repair Mechanisms
            1. 3' to 5' Exonuclease Activity
            2. Mismatch Repair
            3. Base Excision Repair
            4. Nucleotide Excision Repair
      2. Transcription and Gene Expression Regulation
         1. Transcription Initiation
            1. RNA Polymerase II Binding
            2. Transcription Factor Assembly
            3. Promoter Recognition
         2. Transcription Elongation
            1. RNA Polymerase Progression
            2. Elongation Factors
            3. Pausing and Anti-pausing
         3. Transcription Termination
            1. Polyadenylation Signals
            2. Termination Factors
         4. RNA Polymerases
            1. RNA Polymerase I
            2. RNA Polymerase II
            3. RNA Polymerase III
         5. Transcription Factors
            1. General Transcription Factors
            2. Specific Transcription Factors
            3. Activators and Repressors
         6. Enhancers and Silencers
            1. Cis-acting Elements
            2. Trans-acting Factors
            3. Chromatin Looping
         7. Epigenetic Regulation
            1. DNA Methylation
            2. Histone Modifications
            3. Chromatin Remodeling Complexes
      3. RNA Processing
         1. Splicing Mechanism
            1. Spliceosome Assembly
            2. Splice Site Recognition
            3. Transesterification Reactions
         2. Alternative Splicing
            1. Exon Skipping
            2. Intron Retention
            3. Alternative 5' and 3' Splice Sites
            4. Mutually Exclusive Exons
         3. 5' Capping
            1. 7-methylguanosine Cap
            2. Cap-binding Proteins
            3. Cap Function
         4. 3' Polyadenylation
            1. Polyadenylation Signals
            2. Cleavage and Polyadenylation Factors
            3. Poly(A) Tail Function
         5. RNA Editing
            1. A-to-I Editing
            2. C-to-U Editing
            3. Editing Enzymes
      4. Translation and Protein Synthesis
         1. Ribosome Structure and Function
            1. Large Subunit (60S)
            2. Small Subunit (40S)
            3. Ribosomal RNA Components
            4. Ribosomal Proteins
         2. tRNA Charging and Codon Recognition
            1. Aminoacyl-tRNA Synthetases
            2. tRNA Structure
            3. Anticodon-Codon Pairing
         3. Translation Initiation
            1. Ribosome Assembly
            2. Start Codon Recognition
            3. Initiation Factors
         4. Translation Elongation
            1. Peptide Bond Formation
            2. Translocation
            3. Elongation Factors
         5. Translation Termination
            1. Stop Codon Recognition
            2. Release Factors
            3. Ribosome Recycling
         6. Post-Translational Modifications
            1. Protein Folding
            2. Chemical Modifications
            3. Protein Targeting
      5. The Genetic Code
         1. Codon Table
            1. 64 Codons
            2. Amino Acid Assignments
            3. Codon Usage Bias
         2. Start and Stop Codons
            1. AUG Start Codon
            2. UAA Stop Codon
            3. UAG Stop Codon
            4. UGA Stop Codon
         3. Wobble Hypothesis
            1. Third Position Flexibility
            2. Non-Watson-Crick Base Pairs
         4. Degeneracy of the Code
            1. Synonymous Codons
            2. Silent Mutations
            3. Codon Optimization
   3. Genetic Variation
      1. Types of Genetic Variants
         1. Single Nucleotide Polymorphisms (SNPs)
            1. Transition Mutations
            2. Transversion Mutations
            3. SNP Frequency and Distribution
         2. Insertions and Deletions (Indels)
            1. Small Indels
            2. Frameshift Mutations
            3. In-frame Indels
         3. Copy Number Variations (CNVs)
            1. Duplications
            2. Deletions
            3. CNV Formation Mechanisms
         4. Structural Variants
            1. Inversions
               1. Paracentric Inversions
               2. Pericentric Inversions
            2. Translocations
               1. Balanced Translocations
               2. Unbalanced Translocations
            3. Duplications
               1. Tandem Duplications
               2. Segmental Duplications
            4. Large Deletions
               1. Microdeletions
               2. Gross Deletions
      2. Mechanisms of Mutation
         1. Spontaneous Mutations
            1. DNA Replication Errors
            2. Spontaneous Base Modifications
            3. Slipped-Strand Mispairing
         2. Induced Mutations
            1. Chemical Mutagens
            2. Radiation-Induced Mutations
            3. Environmental Mutagens
         3. DNA Replication Errors
            1. Polymerase Errors
            2. Slippage Events
            3. Template Switching
         4. Repair Defects
            1. Mismatch Repair Deficiency
            2. Base Excision Repair Defects
            3. Nucleotide Excision Repair Defects
      3. Polymorphism vs. Pathogenic Variant
         1. Definition of Polymorphism
            1. Population Frequency Criteria
            2. Neutral Variants
            3. Common Variants
         2. Definition of Pathogenic Variant
            1. Disease-Causing Mutations
            2. Functional Impact
            3. Clinical Significance
         3. Variant Classification
            1. Pathogenic
            2. Likely Pathogenic
            3. Uncertain Significance
            4. Likely Benign
            5. Benign
   4. Introduction to Population Genetics
      1. Hardy-Weinberg Equilibrium
         1. Assumptions
            1. Random Mating
            2. No Selection
            3. No Migration
            4. No Mutation
            5. Large Population Size
         2. Calculations
            1. Allele Frequencies
            2. Genotype Frequencies
            3. Hardy-Weinberg Formula
         3. Deviations from Equilibrium
            1. Inbreeding
            2. Population Subdivision
            3. Selection Pressure
      2. Genetic Drift
         1. Random Sampling Effects
         2. Effective Population Size
         3. Bottleneck Effect
            1. Population Reduction
            2. Loss of Genetic Diversity
         4. Founder Effect
            1. New Population Establishment
            2. Genetic Isolation
      3. Gene Flow
         1. Migration Between Populations
         2. Admixture
            1. Population Mixing
            2. Ancestry Proportions
      4. Selection and Fitness
         1. Natural Selection
         2. Fitness Coefficients
         3. Selection Types
      5. Population Stratification
         1. Ancestry Differences
         2. Confounding in Association Studies
         3. Principal Component Analysis