L73: Genetics Of Respiratory Diseases

Question 1

Cystic fibrosis

Answer 1

• Single gene defect (cystic fibrosis gene: chromosome 7)
• Autosomal recessive
• high frequency in white than Asian
• code for cystic fibrosis transmembrane conductance regulator protein (CFTR)
• control Cl- passage in and out
• missing phenylalanine in position 508 of CFTR
  —> missing CFTR / dysfunctional CFTR

1. Thick, sticky mucus (reduce gas exchange, prone to bacterial infection)
2. Pancreatic insufficiency (Cl- and Na+ stay in pancreatic cell —> water stay in cell —> no slurry to carry enzyme away —> digest pancreas —> inflammation, mucus plugs)
3. Salty sweat (inability to reabsorb Cl- —> cannot reabsorb Na+ —> salty)

Diagnosis:
- PCR of defective gene sequence —> gel electrophoresis

Question 2

Asthma

Answer 2

• Continuous/quantitative
• regression to mediocrity
• Due to multiple genes involved (Polygenic) —> each gene small effect —> cumulative effect —> forming a normal distribution curve
• Interplay with environmental factors
  —> tobacco, pollution
  —> salt in diet
  —> lung infections
• Gene: determine susceptibility to disease
• Environment: trigger to bring about the disease

Question 3

Determine whether disease is influenced by genetics

Answer 3

1. Adopted vs Natural children
   - diseased adopted children: ask whether disease run in biological family
   - children adopted away: ask whether adopted child saved from disease

Since Familial tendency can be due to common environment
—> not necessarily genetics

2. Twin study
   - Concordance: Both affected / (1 affected + Both affected) x100
   - totally genetics = 1
   - totally environment = no concordance
   - Monozygotic/identical twins = expected: 1
   - Dizygotic/fraternal twins = expected: 0.5
   - Siblings, parent-child = expected: 0.5
   - Spouse = expect: 0