Genetic Disorders: Understanding Inheritance, Mutations, and Pathology

Genetic Disorders: Understanding Inheritance, Mutations, and Pathology.

Illustrating Inheritance Patterns of Dominant and Recessive Diseases.

Autosomal Dominant Disease: Huntington’s Disease.

Autosomal Recessive Disease: Cystic Fibrosis. Disorder affecting lungs & pancreas, causing thick mucus and breathing problems Mutation in CFTR gene Two copies of faulty gene needed → disease25% chance of child affected if both parents are carriers May skip generations Males & females equally affected Punnett Square Example (Carrier Parents Cc x Cc): Result: 25% unaffected, 50% carrier, 25% affected.

Determining Genetic Cross Outcomes Using Punnett Squares.

Example — Monohybrid Cross. Parent 1 – Aa (heterozygous) Parent 2 – aa (homozygous recessive) Punnett Square: Results: Genotypes: 50% Aa, 50% aa Phenotypes:50% show dominant trait (Aa)50% show recessive trait (aa) Extra Example (Generation crosses): Gen 1: AA × aa → 100% Aa (dominant) Gen 2: Aa × Aa → 75% dominant, 25% recessive.

Inheritance Patterns of Sex-Linked Disorders. Mutations occur on sex chromosomes (X or Y). Males (XY) and Females (XX) inherit differently. Types of Sex-Linked Disorders 1. X-Linked Recessive – Males need 1 faulty allele, females need 2 Examples: Haemophilia, Duchenne muscular dystrophy, red-green color blindness 2. X-Linked Dominant – Single faulty allele affects both genders More severe in males Examples: Rett syndrome, Fragile X syndrome 3. Y-Linked – Only males affected, passed father → son Example: Y-linked infertility.

X-Linked Recessive Disease (Haemophilia). Mutation on the X chromosome Males (XY) need only one faulty allele to show disease Females (XX) need two faulty alleles Punnett Square Example- Carrier mother: XᴴXʰ, Normal father: XᴴY Result: 50% chance male affected, 50% chance female carrier.

X-Linked Dominant Disease (Rett Syndrome). Mutation on X chromosome One faulty allele causes disease in both genders More severe in males Punnett Square Example- Affected mother: XᴿX, Normal father: XY 50% chance affected child (both genders).

Y-Linked Disease (Y-Linked Infertility). Mutation on Y chromosome Only males affected Passed father → son Punnett Square Example- Father: XYʸ (Y chromosome mutation), Mother: XX All sons affected, daughters never affected.

Introduction to Epistasis. Interaction between genes at different loci. One gene can mask, modify, or influence the expression of another gene. Affects the observable traits (phenotype) of an organism. Helps understand complex inheritance patterns beyond Mendelian ratios. Main Types: Recessive Epistasis Dominant Epistasis Complementary Gene Action Duplicate Gene Action Suppression Epistasis.

Examples of Epistasis. EPISTASIS x 5bCc BbCc BC bC bc BC BBCC BBCc BbCC BbCc BBCc BBCC BbCc Bbcc bC BbCC BbCc bbCC bbCc bc BbCc Bbcc bbCc bbcc B - dominant black allele b - recessive brown allele C - dominant coat deposition c - recessive coat deposition.

Additional Epistasis Types. 4. Duplicate Gene Action – Shepherd’s Purse Seed Shape Genes: A & B → Triangular seeds Interaction: At least one dominant → Triangular Phenotypic Ratio: 15:1 (Triangular:Ovoid) 5. Suppression Epistasis – Chicken Feather Color Genes: C = Pigment, I = Inhibitor Interaction: I suppresses C → White feathers Phenotypic Ratio: 13:3 (White:Colored).

Impact of a Single Base Pair Change. A point mutation is a change in one base pair of DNA. It may alter the amino acid sequence, which affects protein structure and function. The impact depends on where and what type of mutation occurs..

Types of Point Mutations. Mutation Type Description Example Effect Silent Change in base but same amino acid GAA → GAG (both Glu) No effect Missense Amino acid replaced with another GAG → GTG Protein shape changes Nonsense Stop codon appears early UAU → UAA Short, nonfunctional protein Frameshift Insertion or deletion shifts reading frame ATG → AATG Entire sequence changes.

Diseases Caused by Single Base Pair Changes. Disease Mutation Type Gene Involved Effect on Protein Sickle Cell Anemia Missense β-globin gene (GAG→GTG) Glutamic acid → Valine; RBCs become sickle-shaped Duchenne Muscular Dystrophy Nonsense Dystrophin gene Premature stop codon → No functional dystrophin Cystic Fibrosis Frameshift CFTR gene (ΔF508) Abnormal chloride channel → Thick mucus.

Evaluation of a Range of Changes to a Single Gene Resulting in Similar Disease Pathology (Cystic Fibrosis Example).

Types of Mutations in the CFTR Gene. Mutation Type Mutation Example Mechanism Impact Deletion ΔF508 Loss of phenylalanine → Misfolded CFTR Most common (70% cases), severe symptoms Missense G551D Guanine → Adenine substitution → Channel doesn’t open properly Moderate severity Nonsense W1282X Premature stop codon → Truncated CFTR protein Severe, early-onset CF.

Comparing Disease Severity and Treatment Approaches.

Genetic Risk Factors in Cancer Development. Genetic risk factors play a key role in serious diseases, especially cancer. Cancer arises from mutations in DNA (inherited or acquired) and environmental influences..

Inherited Genetic Risk Factors. Breast Cancer BRCA1/BRCA2 mutations → lifetime risk: 72% (BRCA1), 69% (BRCA2) Preventive measures: Prophylactic surgery, medications (e.g., Tamoxifen) Colon Cancer Lynch Syndrome (mismatch repair gene mutations) → lifetime risk: 50–70% Early detection via genetic testing allows risk management.

Somatic Mutations & Cancer Risk. Environmental Factors Tobacco Smoking → TP53 mutations → lung cancer Sun Exposure → p53/PTEN mutations → skin cancer Diet → High fat/low fiber → APC mutations → colon cancer Aging → Accumulation of mutations → higher cancer risk (lung, prostate, colon) Interaction of Genetic & Environmental Factors Smoking + BRCA1 mutation → higher breast cancer risk Epigenetic modifications (DNA methylation) can change gene expression without altering DNA sequence.

Managing Genetic Risk & Disease Progression. Genetic Counseling Identifies risk Plans screening/prevention Preventive Measures Prophylactic surgeries (e.g., mastectomy) Medications (e.g., Tamoxifen for BRCA1/2 mutation carriers) Cancer Development Overview Normal cell → tumor suppressor gene inactivated Cell proliferation → DNA repair gene mutation Second tumor suppressor gene mutation → malignant cells.