lecture 14

Question 1

What is hemizygous?

Answer 1

Having one copy of gene (Males are hemizygous for X chromosome)

Question 2

What are genes in Y chromosome responsible for?

Answer 2

spermatogenesis

Question 3

What is psudoautosomal region?

Answer 3

regions of X and Y chromosomes that match, and they line up chromosomes correctly during meiotic recombination.

Question 4

Characterstic of X-linked recessive disorder (4)

Answer 4

1. more common and more severe in males
2. Skipped generations common
3. L-shape (affected male > carrier female > affected male)
4. No male to male transmission

Question 5

What happened if females get disorder for X-linked recessive disorder?

Answer 5

That means that female has skewed X inactivation.

Question 6

Transmission of Glucose 6-phosphate dehydrogenase (G6PD) deficiency

Answer 6

X-linked recessive disorder

Question 7

Transmission of Duchenne muscular dystrophy

Answer 7

X-linked recessive disorder

Question 8

transmission of hemophilia A and B

Answer 8

X-linked recessive disorder

Question 9

Transmission of Lesch-Nyhan syndrome

Answer 9

X-linked recessive disorder

Question 10

What is Lesch-Nyhan syndrome?

Answer 10

Hypoxanthine guanine phosphoribosyl transferase deficiency, which results in hyperuricemia, gout, self mutilation

Question 11

transmission of red-green color blindness

Answer 11

X-linked recessive disorder

Question 12

transmission of SCID (2)

Answer 12

Autosomal recessive and X-linked recessive

mutation in different gene results in same disease

Question 13

Chracteristics of X-linked dominant disorder(5)

Answer 13

1. Skipping of generation not common
2. Preponderance of females compared to males
3. No male to male transmission
4. Variable expressivity in females due to phenomena of X-inactivation.
5. lethal for males

Question 14

Characteristics of Y-linked inheritance(2)

Answer 14

1. Only males show the trait
2. Mutation leads to sterility and are not passed on.
3. Male transmit to all their sons

Question 15

Example of Y-linked inheritance

Answer 15

1. Various mutations in SRY genes
2. H-Y histocompatibility antigen
3. Hairy ears

Question 16

What is SRY gene?

Answer 16

Determine if the person is male or female. So if mutation is on SRY gene, even though person has Y chromosome, mutation leads to development of female characteristics.

Question 17

What can complicate an autosomal dominant pedigree?

Answer 17

Reduced or incomplete penetrance

Question 18

What is characteristic of incomplete penetrance?

Answer 18

1 Skipped generation

Question 19

What is locus heterogeneity?

Answer 19

Mutations at different loci (different genes) that cause the same disease phenotype

Question 20

Example of locus heterogeneity(5)

Answer 20

1. Osteogenesis imperfecta
2. Sensorineural hearing impairment
3. Retinitis pigmentosa
4. Charcot marie Tooth disease (AD,AR,X-linked)
5. SCID (AR and X-linked)

Question 21

What causes osteogenesis imperfecta?

Answer 21

Defect in collagen caused by mutation on chromosome 17 or chromosome 7

Question 22

What is variable expression?

Answer 22

Individuals who have inherited same mutant allele, some individuals are severely affected and other are mildly affected.

Question 23

3 reasons for variable expression

Answer 23

1. Random chance
2. Other genetic factors (modifier loci) or sex influence
3. Environmental exposure

Question 24

How is variable expression explained in hemochromatosis?

Answer 24

Due to sex difference, male has more severe disorder than female, because female release iron through mentruation, reducing iron concentration in the blood.

Question 25

Mode of transmission for xeroderma pigmentosum

Answer 25

autosomal recessive

Question 26

De novo mutation

Answer 26

mutation is transmitted from an unaffected parent to an affected offspring. (usually on hotspot for mutation)

Question 27

Example of de novo mutation

Answer 27

1. Neurofibromatosis (NF1)
2. Achondroplasia
3. Duchenne muscular dystrophy (about 33% is de novo)
4. Osteogenesis imperfecta,
5. Marfan syndrome

Question 28

The relationship between paternal age and de novo autosomal dominant mutation

Answer 28

Higher paternal age, higher chance of de novo autosomal dominant mutation.

Question 29

Characteristic of denovo mutation pedigree

Answer 29

2 skipped generation for autosomal dominant mutation

Question 30

When does de novo mutation occur?

Answer 30

During gamete formation, which is not in the parents original genome.

Question 31

When could de novo mutation for X-linked recessive occur?

Answer 31

in single sperm from dad or
in single ovum from mom or
in fertilized egg occuring soon after conception

Question 32

How is germline mosaicism different from de novo mutation?

Answer 32

For new mutation, there is a single child with a disorder and no family history of the disorder, but for germline mosaicism, more than 1 are affected, parents should shoe mutation in their germline but normal peripheral cells.

Question 33

Examples of disease that shows delayed age of onset(3)

Answer 33

1. Huntington disease
2. Hemochromatosis
3. Familial breast cancer