AR Diseases

Question 1

• Majority of mutant alleles where?
• Compound heterozygote?
• Allelic heterogeneity?

Answer 1

• With carriers
• 2 different mutant alleles at same loci can affect severity
• Multiple alleles of a single gene

Question 2

• PKU: Def?
• High where? Low where?
• Phenotype?
• 2 types?
• Screening?
• Treatment?

Answer 2

• High phenylalanine in blood
• Scotland, Finland
• High PA in blood and urine, microcephaly, epilepsy
• 1.) most common = defective PAH enzyme (PA-Tyrosine)
  2. ) Defective PAH cofactor = effects other enzymes as well
• Mass spec; but timing is important so mom’s blood is out of baby
• Diet, especially for pregnant women who can hurt even unaffected child; type 2 needs neurotransmitter drug added as well

Question 3

Alpha 1 - antitrypsin (ATD) deficiency: Def?

• Phenotype?
• Ecogenetics involved how?
• Mechanism involved?
• Possible genotypes? Results in?

Answer 3

• Deficient in SERPINA1 protease inhibitor
• Emphesyma, liver cancer, cihrossis
• Smoking effects severity
• Serpina1 inhibits eleastase (released by neutrophils) which inhibits elastin (allows elasticity)
• Z/Z = 15% of normal function
• S/S = 60% of normal function
• S/Z = somewhere in between

Question 4

Tay-Sachs (untreatable): Def? Prominent in?

• Phenotype?
• Mechanism?
• 3 types? Gene affected? Protein affected? Substrate? Enzyme Test?
• Which activated by heat?
• Testing options? (3)

Answer 4

• Fatal disorder with destruction of CNS; Ashkenazi Jews
• Muscle weakness, seizures, mental retardation, vegetative state
• Lysosomal storage disorder (defective HexA enzyme) where they can’t degrade ganglioside
• 1.) TS = HexA; alpha subunit; gangliosides; Hex A defective; activated by heat
  2. ) Sandhoffs: HexB; B subunit; globosides; both defective
  3. ) AB variant: GM2AP; activator of A and B affected; x; both normal
• DNA testing, carrier enzyme screen, amniotic fluid test