Genetics Lecture Notes

Overview of Genetic Disorders

1. Classifications of Genetic Disorders:

   • Three wings of disorders:
     • Single-Gene Disorders: Caused by mutations in a single gene, e.g., cystic fibrosis, sickle cell anemia.
     • Complex Disorders: Involving multiple genes and environmental factors, e.g., diabetes, hypertension.
     • Chromosomal Disorders: Involving structural changes in chromosomes, e.g., Down syndrome.

2. Mutation Types and Effects:

   • Point Mutation: Change in a single DNA base pair.
     • Examples: Sickle cell anemia (substitution).
   • Insertions/Deletions: Addition or loss of a DNA segment.
     • Examples: Cystic fibrosis (deletion of three bases).
   • Frame Shift Mutation: Insertions or deletions that alter the reading frame of a gene.
   • Trinucleotide Repeat Expansion: Repeated sequence of three nucleotides, leading to diseases like Huntington's.

3. Structural Chromosome Changes:

   • Translocations: Part of a chromosome breaks off and attaches to another.
   • Inversions: A chromosome segment breaks inverts and reattaches.
   • Ring Chromosomes: A chromosome segment breaks off and forms a ring.

Inheritance Patterns

1. Autosomal Dominant Disorders

   • Characteristics: Manifest in heterozygous state, both males and females affected equally. One affected parent usually leads to a 50% chance of disease transmission in offspring.
   • Examples: Huntington's disease, Neurofibromatosis type 1.

2. Autosomal Recessive Disorders

   • Characteristics: Manifest in homozygous state, both males and females affected, often seen in consanguineous relationships. Parents typically unaffected carriers.
   • Examples: Cystic fibrosis, Sickle cell anemia.

3. X-linked Disorders

   • X-linked Recessive: Males typically more affected because they have only one X chromosome. Females are carriers.
     • Examples: Hemophilia, Duchenne muscular dystrophy.
   • X-linked Dominant: Both males and females can be affected, but females more frequently because they have two X chromosomes.
     • Examples: Vitamin D resistant rickets.

4. Other Inheritance Patterns

   • Non-Mendelian inheritance: Includes mitochondrial inheritance and trinucleotide repeat disorders.

Key Concepts of Mutations

1. Mutations Impact on Function:
   • Loss of Function: Mutation results in reduced or absence of normal function, e.g., cystic fibrosis.
   • Gain of Function: Mutation results in a new or enhanced activity, e.g., Huntington's disease.
   • Dominant Negative: The mutant gene product interferes with the function of the normal protein, e.g., certain forms of Osteogenesis Imperfecta.

Genetic Counseling and Impact

1. Importance of Genetic Counseling
   • Helps in understanding and managing risks associated with genetic disorders.
2. Pedigree Analysis
   • Used to determine inheritance patterns and likelihoods of offspring being affected.
3. Applications of Genetics in Medicine
   • Predictive testing, prenatal diagnosis, and personalized medicine are evolving areas influenced by genetic understanding.

Conclusion

Understanding the classification, types, and inheritance patterns of genetic disorders allows for better management and counseling of affected individuals and their families. The interplay of genetic and environmental factors contributes significantly to the manifestation and progression of these disorders.