Exam #5: Single Gene Disorders Flashcards Preview

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Flashcards in Exam #5: Single Gene Disorders Deck (37):
1

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

2

Null Mutation

Destroys a protein

3

Loss of Function Mutation

Reduce protein activity

4

Gain of Function Mutation

Alter protein function and/or convey a new function

5

Dominant Alleles

Produce phenotype in heterozygous state

6

Recessive Alleles

Produce phenotype in homozygous state

7

Carrier

Patient w/ one defective allele but without disease

8

Compound heterozygote

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

9

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

10

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

11

Haploinsufficiency

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

12

Dominant Negative Effect

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

13

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

14

Lack of Backup

- Cancer development after inactivation of both alleles i.e. the "two hit" model
- E.g. Rb

15

What determines sex in humans?

Presence or absence of Y chromosome

16

Why are X chromosome mutations in men dominant?

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

17

Why are females mosaics for X chromosomes?

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

18

Mitochondrial Gene Defects

DO NOT follow mendelian rules of inheritance

19

Who are mitochondrial defects inherited from?

Mother

20

Why is there variable expression of mitochondrial defects?

Cells have many mitochondria with many copies of the chromosome

21

Consanguineous Mating

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

22

Coefficient of inbreeding

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

23

Autosomal Recessive Pedigree

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

24

Autosomal Dominant Pedigree

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

25

Incomplete penetrance

Not all people with disease genotype having phenotype

26

Expressivity

How severe a disease phenotype is

27

Neurofibromatosis Type 1

- Complete penetrance
- Variable expressivity

28

Premutation

- 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

29

Huntington Disease

- Permutation
- Anticipation

30

Anticipation

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

31

Fitness

Chance of reproduction

32

Mutation Hotspot

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

33

Ova Mutations

Nondisjunction

34

Sperm Mutations

Point Mutation

35

X-linked Recessive Pedigree

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

36

X-Linked Dominant Pedigree

- Male transmits to all of his daughters
- Female transmits to half of children regardless of sex

37

Mitochondrial Inheritance Pedigree

Mothers pass to all of their children