Exam #5: Single Gene Disorders Flashcards
What are the five functions of proteins that can be impaired in the single-gene disorders?
1) Protein with catalytic activity (Enzymes) - Recessive
2) Proteins involved in transport & storage - Recessive
3) Proteins with structural function
4) Proteins involved in growth, differentiation, & development
5) Receptor & signaling proteins
Null Mutation
Destroys a protein
Loss of Function Mutation
Reduce protein activity
Gain of Function Mutation
Alter protein function and/or convey a new function
Dominant Alleles
Produce phenotype in heterozygous state
Recessive Alleles
Produce phenotype in homozygous state
Carrier
Patient w/ one defective allele but without disease
Compound heterozygote
Patient w/ two defective but non-identical alleles leading to disease phenotype
What defects generally show recessive inheritance? Why?
1) Enzyme defects
2) Mutations in proteins involved in transport & storage
- One functional allele remains
- Loss can be compensated for by regulatory mechanisms
What defects generally show dominant inheritance?
1) Structural protein defects
2) Defects in proteins involved in growth, differentiation & development
3) Defects in receptors & signaling proteins
Haploinsufficiency
Half of the gene does is not sufficient for the cell to carry out its function
Dominant Negative Effect
- Mutation produces an abnormal protein that may compete with the wildtype form and impair function
- E.g. structural proteins
Gain of Function Mutation
- IF mutation produces a protein with a new function, it will have an effect no matter how many wildtype forms of a protein are present
- Signal transduction proteins
Lack of Backup
- Cancer development after inactivation of both alleles i.e. the “two hit” model
- E.g. Rb
What determines sex in humans?
Presence or absence of Y chromosome
Why are X chromosome mutations in men dominant?
They only have one copy of the genes b/c they only have one X chromosome
Why are females mosaics for X chromosomes?
One is inactivated early during embryogenesis in a RANDOM but FIXED manner
Mitochondrial Gene Defects
DO NOT follow mendelian rules of inheritance
Who are mitochondrial defects inherited from?
Mother
Why is there variable expression of mitochondrial defects?
Cells have many mitochondria with many copies of the chromosome
Consanguineous Mating
Mating of closely related individuals that increases risk for development of recessive disease
Coefficient of inbreeding
- Degree of homozygosity of a child
- 1/4 for siblings
- 1/8 for first cousins
Autosomal Recessive Pedigree
- Affected children usually have normal parents
- Both sexes are equally affected
- Consanguinity is often present
Autosomal Dominant Pedigree
- Affected child has at least one affected parent
- Both sexes are equally affected
- Disease can be transmitted from father to son
