Pathophysiology 1: Genetic Diseases - Lecture Notes

Overview

• Focus on Genetic Diseases
  • Mutations
  • Chromosomal Aberrations/Alterations
  • Transmission of Genetic Diseases

DNA Structure and Replication

• DNA Replication
  • Occurs during S phase of interphase
  • Unwinding and unzipping of DNA needed for replication
  • Nitrogenous Bases: Cytosine (C), Guanine (G), Adenine (A), Thymine (T)
  • Complementary base pairing: C-G, A-T
  • DNA Polymerase helps in forming two DNA strands from one

Transcription and Translation

• Purpose of DNA
  • Carries genetic information for protein synthesis
• Transcription
  • Occurs in the nucleus
  • DNA segment (gene) is copied into mRNA
  • Uses Uracil (U) instead of Thymine (T)
  • mRNA travels to ribosome for protein synthesis
• Translation
  • Codon: Set of 3 nucleotides, read by ribosome
  • tRNA brings specific amino acids to ribosome
  • Anticodon on tRNA matches with codon
  • Polypeptide formation depends on amino acid sequence
• Mutations can alter protein function

Types of Mutations

• Mutations: Change in the sequence of a gene
  • Can be inherited or occur spontaneously
• Mutagen
  • Physical: Ionizing radiation (e.g., X-rays)
  • Chemical: Formaldehyde, Sodium Nitrate
  • Biological: Viruses (e.g., HIV)
• Types of Mutations
  • Base Pair Substitutions:
    • Missense: Single amino acid change
    • Nonsense: Introduces stop codon, truncated proteins
  • Frameshift Mutations:
    • Insertions or deletions, alter entire reading frame

Chromosomal Aberrations

• Numerical Aberrations
  • Euploid cells are normal (46 chromosomes for somatic, 23 for gametes)
  • Polyploidy: More than normal number (e.g., triploidy, tetraploidy)
  • Aneuploidy: Abnormal number of a single chromosome
    • Monosomy: Missing one chromosome
    • Trisomy: Extra chromosome (e.g., Down Syndrome)
• Structural Aberrations
  • Deletions: Loss of chromosome segment
  • Duplications: Gain of extra chromosome segment
  • Inversions: Two breaks, reinsertion in reverse order
  • Translocations: Exchange between non-homologous chromosomes
    • Reciprocal Translocations: Exchange between homologous chromosomes

Transmission of Genetic Diseases

• Genetically Inherited: Passed from parents
• Congenital: Present at birth, may not be inherited
• Recessive vs. Dominant
  • Recessive: Requires two copies to show disease
  • Dominant: Single copy can show disease
• Penetrance and Expressivity
  • Penetrance: Proportion showing disease
  • Expressivity: Severity of disease manifestation

Inheritance Patterns

• Single Gene Diseases
  • Retinoblastoma: Dominant
  • Cystic Fibrosis: Recessive
• Multifactorial Diseases: Influenced by genes and environment
  • Examples: Cancer, Diabetes, Heart Disease

Genetic Testing

• Prenatal Diagnosis
  • Amniocentesis: Sampling amniotic fluid
  • Chorionic Villus Sampling (CVS): Sampling placental tissue

Summary

• Understanding genetic diseases involves mutations, chromosomal alterations, and inheritance patterns
• Genetic testing can aid in early identification of potential genetic disorders