Single Gene Disorders

Question 1

What are the modes of inheritance?

Answer 1

• autosomal recessive: “horizontal transmission,” need two recessive alleles to be affected
• autosomal dominant: “veritcal transmission,” need only one dominant allele to be affected
• X-linked recessive: more males than females affected, no father to son transmission
  
  • males: one affected X needed
  • females: two affected Xs needed
• X-linked dominant: more females than males affected, vertical transmission, no father to son transmission
  
  • only one affected X needed
• mitochondrial inheritance:

Question 2

Compound heterozygote vs. homozygote

Answer 2

with autosomal recessive inheritance, often the heterozygote parents each have a different version of the recessive allele –> affected child has two recessive alleles that are different mutations but still produce the recessive phenotype

Question 3

Why are some mutations dominant?

Answer 3

• Haploinsufficiency: half of normal amount of protein in not enough
  
  • ex. familiar hypercholesterolemia
• Dominant negative effect: mutant protein interferes with function of normal protien
  
  • ex. osteogenesis imperfecta type II
• Gain of function: new or enhanced property of protein
  
  • ex. Huntington disease: cytotoxic protein

Question 4

Allelic Heterogeneity

Answer 4

diffrent mutations in the same locus produce the same or similar phenotype

(more than one mutant allele)

Question 5

Locus Heterogeneity

Answer 5

mutations in different genes produce similar phenotypes

Question 6

Penetrance

Answer 6

likelihood that the disease allele will result in the disease; can sometimes be incomplete

Question 7

Delayed Onset

Answer 7

individual may pass the mutant allele on to offspring but die of unrelated causes prior to showing the disease

Question 8

Germline Mosaicism

Answer 8

• Mosaicism results when a mutation occurs in one cell of a multicellular embryo
• Only some of the cells in that person would be mutant, and depending on which cells/tissues have the mutation, the individual could be clinically normal
• If the individual’s has a mixture of gametes with the normal and the mutant allele, the mutation could be passed on to children

Question 9

Pleiotropy

Answer 9

one gene contributes to multiple phenotypic effects

ex. Marfan syndrome

Question 10

Variable expressivity

Answer 10

phenotype varies amoung individuals with same genotype

Question 11

Why do the same mutations show differences in penetrancea nd expressivity?

Answer 11

• modifier genes
• environmental factors
• complexe gene and environmental interactions