Exam #5: Single Gene Disorders

Question 1

What are the five functions of proteins that can be impaired in the single-gene disorders?

Answer 1

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

Question 2

Null Mutation

Answer 2

Destroys a protein

Question 3

Loss of Function Mutation

Answer 3

Reduce protein activity

Question 4

Gain of Function Mutation

Answer 4

Alter protein function and/or convey a new function

Question 5

Dominant Alleles

Answer 5

Produce phenotype in heterozygous state

Question 6

Recessive Alleles

Answer 6

Produce phenotype in homozygous state

Question 7

Carrier

Answer 7

Patient w/ one defective allele but without disease

Question 8

Compound heterozygote

Answer 8

Patient w/ two defective but non-identical alleles leading to disease phenotype

Question 9

What defects generally show recessive inheritance? Why?

Answer 9

1) Enzyme defects
2) Mutations in proteins involved in transport & storage

• One functional allele remains
• Loss can be compensated for by regulatory mechanisms

Question 10

What defects generally show dominant inheritance?

Answer 10

1) Structural protein defects
2) Defects in proteins involved in growth, differentiation & development
3) Defects in receptors & signaling proteins

Question 11

Haploinsufficiency

Answer 11

Half of the gene does is not sufficient for the cell to carry out its function

Question 12

Dominant Negative Effect

Answer 12

• Mutation produces an abnormal protein that may compete with the wildtype form and impair function
• E.g. structural proteins

Question 13

Gain of Function Mutation

Answer 13

• 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

Question 14

Lack of Backup

Answer 14

• Cancer development after inactivation of both alleles i.e. the “two hit” model
• E.g. Rb

Question 15

What determines sex in humans?

Answer 15

Presence or absence of Y chromosome

Question 16

Why are X chromosome mutations in men dominant?

Answer 16

They only have one copy of the genes b/c they only have one X chromosome

Question 17

Why are females mosaics for X chromosomes?

Answer 17

One is inactivated early during embryogenesis in a RANDOM but FIXED manner

Question 18

Mitochondrial Gene Defects

Answer 18

DO NOT follow mendelian rules of inheritance

Question 19

Who are mitochondrial defects inherited from?

Answer 19

Mother

Question 20

Why is there variable expression of mitochondrial defects?

Answer 20

Cells have many mitochondria with many copies of the chromosome

Question 21

Consanguineous Mating

Answer 21

Mating of closely related individuals that increases risk for development of recessive disease

Question 22

Coefficient of inbreeding

Answer 22

• Degree of homozygosity of a child
• 1/4 for siblings
• 1/8 for first cousins

Question 23

Autosomal Recessive Pedigree

Answer 23

• Affected children usually have normal parents
• Both sexes are equally affected
• Consanguinity is often present

Question 24

Autosomal Dominant Pedigree

Answer 24

• Affected child has at least one affected parent
• Both sexes are equally affected
• Disease can be transmitted from father to son

Question 25

Incomplete penetrance

Answer 25

Not all people with disease genotype having phenotype

Question 26

Expressivity

Answer 26

How severe a disease phenotype is

Question 27

Neurofibromatosis Type 1

Answer 27

• Complete penetrance

- Variable expressivity

Question 28

Premutation

Answer 28

• Seen in diseases caused by a specific number of repeats
• Individual close to carrying number of repeats for disease phenotype but not yet
• High chance of producing gametes with pathogenic number of repeats

Question 29

Huntington Disease

Answer 29

• Permutation

- Anticipation

Question 30

Anticipation

Answer 30

• Severity of disease phenotype increases when transmitted through a pedigree
• Seen in repeat expansion diseases

Question 31

Fitness

Answer 31

Chance of reproduction

Question 32

Mutation Hotspot

Answer 32

• Chromosomal region where mutations occur frequently
• CG dinucleotide repeat is common example
• Cytosine is methylated to methylcytosine & deaminated, yielding tymine

Question 33

Ova Mutations

Answer 33

Nondisjunction

Question 34

Sperm Mutations

Answer 34

Point Mutation

Question 35

X-linked Recessive Pedigree

Answer 35

• No father-son transmission
• Affected boys usually have unaffected parents
• Males are affected more frequently than girls

Question 36

X-Linked Dominant Pedigree

Answer 36

• Male transmits to all of his daughters

- Female transmits to half of children regardless of sex

Question 37

Mitochondrial Inheritance Pedigree

Answer 37

Mothers pass to all of their children