Medical Genetics

  1. Patterns of Inheritance
    1. Pedigree Analysis
      1. Symbols and Nomenclature
        1. Standard Pedigree Symbols
          1. Affected Individuals
            1. Carriers
              1. Deceased Individuals
                1. Consanguineous Matings
                2. Constructing a Pedigree
                  1. Information Gathering
                    1. Three-Generation Rule
                      1. Documentation Standards
                      2. Interpreting Pedigree Patterns
                        1. Identifying Inheritance Patterns
                          1. Vertical vs. Horizontal Transmission
                            1. Male vs. Female Affected Ratios
                              1. Generation Skipping
                              2. Recognizing Consanguinity
                                1. Coefficient of Inbreeding
                                  1. Increased Recessive Disease Risk
                                  2. Identifying De Novo Mutations
                                    1. Sporadic Cases
                                      1. New Mutations
                                        1. Gonadal Mosaicism
                                    2. Mendelian Inheritance
                                      1. Autosomal Dominant Inheritance
                                        1. Characteristics and Risk
                                          1. 50% Risk to Offspring
                                            1. Male and Female Equally Affected
                                              1. Vertical Transmission Pattern
                                              2. Vertical Transmission
                                                1. Parent-to-Child Transmission
                                                  1. Multiple Generations Affected
                                                  2. Reduced Penetrance
                                                    1. Incomplete Expression
                                                      1. Environmental Factors
                                                      2. Variable Expressivity
                                                        1. Phenotypic Variation
                                                          1. Severity Differences
                                                            1. Modifier Genes
                                                            2. Example Disorders
                                                              1. Huntington's Disease
                                                                1. CAG Repeat Expansion
                                                                  1. Anticipation
                                                                    1. Adult Onset
                                                                    2. Marfan Syndrome
                                                                      1. Connective Tissue Disorder
                                                                        1. FBN1 Gene
                                                                          1. Multisystem Involvement
                                                                          2. Familial Hypercholesterolemia
                                                                            1. LDLR Gene
                                                                              1. Cardiovascular Risk
                                                                                1. Heterozygote vs. Homozygote
                                                                            2. Autosomal Recessive Inheritance
                                                                              1. Characteristics and Risk
                                                                                1. 25% Risk to Offspring
                                                                                  1. Male and Female Equally Affected
                                                                                    1. Horizontal Transmission Pattern
                                                                                    2. Horizontal Transmission
                                                                                      1. Affected Siblings
                                                                                        1. Unaffected Parents
                                                                                        2. Consanguinity
                                                                                          1. Rare Allele Sharing
                                                                                          2. Carrier State
                                                                                            1. Heterozygous Carriers
                                                                                              1. Usually Asymptomatic
                                                                                                1. Carrier Testing
                                                                                                2. Example Disorders
                                                                                                  1. Cystic Fibrosis
                                                                                                    1. CFTR Gene
                                                                                                      1. Chloride Channel Defect
                                                                                                        1. Respiratory and Digestive Symptoms
                                                                                                        2. Sickle Cell Anemia
                                                                                                          1. HBB Gene
                                                                                                            1. Hemoglobin Variant
                                                                                                              1. Vaso-occlusive Crises
                                                                                                              2. Phenylketonuria
                                                                                                                1. PAH Gene
                                                                                                                  1. Phenylalanine Metabolism
                                                                                                                    1. Intellectual Disability Prevention
                                                                                                                2. X-Linked Recessive Inheritance
                                                                                                                  1. Characteristics and Risk
                                                                                                                    1. Affected Males
                                                                                                                      1. Carrier Females
                                                                                                                        1. No Male-to-Male Transmission
                                                                                                                        2. Affected Males vs. Carrier Females
                                                                                                                          1. Hemizygous Males
                                                                                                                            1. Heterozygous Females
                                                                                                                              1. X-Inactivation in Females
                                                                                                                              2. Skewed X-Inactivation
                                                                                                                                1. Non-random Inactivation
                                                                                                                                  1. Manifesting Heterozygotes
                                                                                                                                  2. Example Disorders
                                                                                                                                    1. Duchenne Muscular Dystrophy
                                                                                                                                      1. DMD Gene
                                                                                                                                        1. Dystrophin Deficiency
                                                                                                                                          1. Progressive Muscle Weakness
                                                                                                                                          2. Hemophilia A
                                                                                                                                            1. F8 Gene
                                                                                                                                              1. Factor VIII Deficiency
                                                                                                                                                1. Bleeding Disorder
                                                                                                                                                2. Red-Green Color Blindness
                                                                                                                                                  1. OPN1LW and OPN1MW Genes
                                                                                                                                                    1. Opsin Defects
                                                                                                                                                      1. Visual Perception
                                                                                                                                                  2. X-Linked Dominant Inheritance
                                                                                                                                                    1. Characteristics and Risk
                                                                                                                                                      1. Affected Females and Males
                                                                                                                                                        1. More Affected Females
                                                                                                                                                          1. Vertical Transmission
                                                                                                                                                          2. Affected Females vs. Males
                                                                                                                                                            1. Female Predominance
                                                                                                                                                              1. Male Severity
                                                                                                                                                              2. Male Lethality
                                                                                                                                                                1. Embryonic or Fetal Death
                                                                                                                                                                  1. Surviving Males Rare
                                                                                                                                                                  2. Example Disorders
                                                                                                                                                                    1. Rett Syndrome
                                                                                                                                                                      1. MECP2 Gene
                                                                                                                                                                        1. Neurodevelopmental Disorder
                                                                                                                                                                          1. Female Predominance
                                                                                                                                                                          2. Fragile X Syndrome
                                                                                                                                                                            1. FMR1 Gene
                                                                                                                                                                              1. CGG Repeat Expansion
                                                                                                                                                                                1. Intellectual Disability
                                                                                                                                                                            2. Y-Linked Inheritance
                                                                                                                                                                              1. Characteristics and Risk
                                                                                                                                                                                1. Male-Only Transmission
                                                                                                                                                                                  1. Father-to-Son Inheritance
                                                                                                                                                                                    1. Patrilineal Inheritance
                                                                                                                                                                                    2. Male-to-Male Transmission
                                                                                                                                                                                      1. Direct Paternal Inheritance
                                                                                                                                                                                        1. No Recombination
                                                                                                                                                                                        2. Example Disorders
                                                                                                                                                                                          1. Y Chromosome Infertility
                                                                                                                                                                                            1. Azoospermia Factor Deletions
                                                                                                                                                                                        3. Non-Mendelian Inheritance
                                                                                                                                                                                          1. Mitochondrial Inheritance
                                                                                                                                                                                            1. Maternal Transmission
                                                                                                                                                                                              1. Maternal Inheritance Pattern
                                                                                                                                                                                                1. Cytoplasmic Inheritance
                                                                                                                                                                                                  1. Oocyte Contribution
                                                                                                                                                                                                  2. Heteroplasmy
                                                                                                                                                                                                    1. Mixed Mitochondrial Populations
                                                                                                                                                                                                      1. Variable Expression
                                                                                                                                                                                                        1. Tissue-Specific Effects
                                                                                                                                                                                                        2. Threshold Effect
                                                                                                                                                                                                          1. Critical Mutation Load
                                                                                                                                                                                                            1. Tissue Energy Requirements
                                                                                                                                                                                                            2. Example Disorders
                                                                                                                                                                                                              1. MELAS Syndrome
                                                                                                                                                                                                                1. Leber Hereditary Optic Neuropathy
                                                                                                                                                                                                                  1. Mitochondrial Myopathies
                                                                                                                                                                                                                2. Genomic Imprinting and Uniparental Disomy
                                                                                                                                                                                                                  1. Mechanisms of Imprinting
                                                                                                                                                                                                                    1. DNA Methylation
                                                                                                                                                                                                                      1. Histone Modifications
                                                                                                                                                                                                                        1. Imprinting Control Regions
                                                                                                                                                                                                                        2. Prader-Willi Syndrome
                                                                                                                                                                                                                          1. 15q11-q13 Deletion
                                                                                                                                                                                                                            1. Paternal Deletion
                                                                                                                                                                                                                              1. Maternal UPD15
                                                                                                                                                                                                                              2. Angelman Syndrome
                                                                                                                                                                                                                                1. 15q11-q13 Deletion
                                                                                                                                                                                                                                  1. Maternal Deletion
                                                                                                                                                                                                                                    1. Paternal UPD15
                                                                                                                                                                                                                                    2. Uniparental Disomy Types
                                                                                                                                                                                                                                      1. Heterodisomy
                                                                                                                                                                                                                                        1. Isodisomy
                                                                                                                                                                                                                                          1. Mechanisms of Formation
                                                                                                                                                                                                                                        2. Mosaicism
                                                                                                                                                                                                                                          1. Somatic Mosaicism
                                                                                                                                                                                                                                            1. Post-zygotic Mutations
                                                                                                                                                                                                                                              1. Tissue Distribution
                                                                                                                                                                                                                                                1. Clinical Variability
                                                                                                                                                                                                                                                2. Germline Mosaicism
                                                                                                                                                                                                                                                  1. Gonadal Mosaicism
                                                                                                                                                                                                                                                    1. Recurrence Risk
                                                                                                                                                                                                                                                      1. Parental Testing Limitations
                                                                                                                                                                                                                                                      2. Clinical Implications
                                                                                                                                                                                                                                                        1. Phenotypic Variability
                                                                                                                                                                                                                                                          1. Diagnostic Challenges
                                                                                                                                                                                                                                                            1. Genetic Counseling Issues
                                                                                                                                                                                                                                                          2. Dynamic Mutations
                                                                                                                                                                                                                                                            1. Mechanism of Repeat Expansion
                                                                                                                                                                                                                                                              1. Trinucleotide Repeats
                                                                                                                                                                                                                                                                1. Replication Slippage
                                                                                                                                                                                                                                                                  1. DNA Repair Errors
                                                                                                                                                                                                                                                                  2. Anticipation
                                                                                                                                                                                                                                                                    1. Increasing Severity
                                                                                                                                                                                                                                                                      1. Earlier Onset
                                                                                                                                                                                                                                                                        1. Generational Progression
                                                                                                                                                                                                                                                                        2. Premutation States
                                                                                                                                                                                                                                                                          1. Intermediate Alleles
                                                                                                                                                                                                                                                                            1. Reduced Penetrance
                                                                                                                                                                                                                                                                              1. Expansion Risk
                                                                                                                                                                                                                                                                              2. Example Disorders
                                                                                                                                                                                                                                                                                1. Huntington's Disease
                                                                                                                                                                                                                                                                                  1. CAG Repeats in HTT
                                                                                                                                                                                                                                                                                    1. Polyglutamine Expansion
                                                                                                                                                                                                                                                                                    2. Fragile X Syndrome
                                                                                                                                                                                                                                                                                      1. CGG Repeats in FMR1
                                                                                                                                                                                                                                                                                        1. Gene Silencing
                                                                                                                                                                                                                                                                                        2. Myotonic Dystrophy
                                                                                                                                                                                                                                                                                          1. CTG Repeats
                                                                                                                                                                                                                                                                                            1. RNA Toxicity
                                                                                                                                                                                                                                                                                      2. Complex Inheritance
                                                                                                                                                                                                                                                                                        1. Polygenic Traits vs. Multifactorial Traits
                                                                                                                                                                                                                                                                                          1. Multiple Gene Effects
                                                                                                                                                                                                                                                                                            1. Environmental Interactions
                                                                                                                                                                                                                                                                                              1. Continuous Variation
                                                                                                                                                                                                                                                                                              2. Role of Genetic and Environmental Factors
                                                                                                                                                                                                                                                                                                1. Gene-Environment Interactions
                                                                                                                                                                                                                                                                                                  1. Environmental Triggers
                                                                                                                                                                                                                                                                                                    1. Lifestyle Factors
                                                                                                                                                                                                                                                                                                    2. Quantitative Traits and the Threshold Model
                                                                                                                                                                                                                                                                                                      1. Liability Distribution
                                                                                                                                                                                                                                                                                                        1. Threshold for Disease
                                                                                                                                                                                                                                                                                                          1. Risk Factors
                                                                                                                                                                                                                                                                                                          2. Heritability
                                                                                                                                                                                                                                                                                                            1. Genetic Contribution
                                                                                                                                                                                                                                                                                                              1. Environmental Contribution
                                                                                                                                                                                                                                                                                                                1. Population-Specific Estimates
                                                                                                                                                                                                                                                                                                                2. Recurrence Risk Calculation
                                                                                                                                                                                                                                                                                                                  1. Empirical Risk Figures
                                                                                                                                                                                                                                                                                                                    1. Family History Assessment
                                                                                                                                                                                                                                                                                                                      1. Risk Modification Factors
                                                                                                                                                                                                                                                                                                                      2. Examples
                                                                                                                                                                                                                                                                                                                        1. Diabetes Mellitus
                                                                                                                                                                                                                                                                                                                          1. Type 1 Diabetes
                                                                                                                                                                                                                                                                                                                            1. Type 2 Diabetes
                                                                                                                                                                                                                                                                                                                              1. Genetic Risk Factors
                                                                                                                                                                                                                                                                                                                              2. Heart Disease
                                                                                                                                                                                                                                                                                                                                1. Coronary Artery Disease
                                                                                                                                                                                                                                                                                                                                  1. Genetic Susceptibility
                                                                                                                                                                                                                                                                                                                                    1. Environmental Risk Factors
                                                                                                                                                                                                                                                                                                                                    2. Neural Tube Defects
                                                                                                                                                                                                                                                                                                                                      1. Spina Bifida
                                                                                                                                                                                                                                                                                                                                        1. Anencephaly
                                                                                                                                                                                                                                                                                                                                          1. Folate Prevention
                                                                                                                                                                                                                                                                                                                                          2. Cleft Lip and Palate
                                                                                                                                                                                                                                                                                                                                            1. Orofacial Clefts
                                                                                                                                                                                                                                                                                                                                              1. Genetic Factors
                                                                                                                                                                                                                                                                                                                                                1. Environmental Factors

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                                                                                                                                                                                                                                                                                                                                          1. Fundamentals of Human Genetics and Genomics

                                                                                                                                                                                                                                                                                                                                          Go to top

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                                                                                                                                                                                                                                                                                                                                          3. Cytogenetics