Lecture 11 Way Beyond Mendel

Question 1

Define Epistasis

Answer 1

Epistasis occurs when one gene masks the effects of another gene.

Question 2

How does dominant epistasis alter the F2 phenotypic ratio

Answer 2

12:3:1 ratio

Question 3

How does recessive epistasis alter the F2 phenotypic ratio

Answer 3

9:4:3 ratio

Question 4

Define Pleiotropy

Answer 4

Occurs when a single gene controls multiple phenotypes.

Question 5

Give two reasons why not all individuals with the same genotype would express the same phenotype

Answer 5

1) incomplete penetrance

2) Variable expressivity

Question 6

List the two factors responsible for varying phenotypic expression between individuals of a population

Answer 6

• Penetrance

- Expressivity

Question 7

Define Penetrance

Answer 7

Penetrance is a measure of the percentage of individuals of a csertain genotype express the phenotype

Question 8

Define Expressivity

Answer 8

Expressivity is a measure of

Question 9

Explain what is meant by genomic imprinting

Answer 9

This is where one of the maternal or paternal allele is imprinted via an epigenetic tag and silenced. Once silenced, this allele can no longer be expressed.

Question 10

Define Maternal imprinting

Answer 10

• The maternal allele is imprinted via addition of an epigenetic tag
• Maternal allele is silenced
• The paternal allele is preferentially expressed in the phenotype.

Question 11

Define Paternal imprinting

Answer 11

• The paternal allele is imprinted via addition of an epigenetic tag
• Paternal allele silenced
• Only the maternal allele is preferentially expressed in the embryo.

Question 12

Give an example of a maternally imprinted/silenced gene

Answer 12

The insulin growth factor 2 gene

Question 13

Give an example of Maternal imprinting

Answer 13

• Insulin growth factor 2 gene in mice
• The IGF2 has 2 alleles, a mutant and wildtype.
• The maternal igf2 allele is silenced.
• The paternal allele is expressed only.
• The paternal allele is

Question 14

Give examples of pleiotropies

Answer 14

Pulmonary ciliary disease that is due to a mutation in cilia - affects multiple systems

Achondroplasia - recessive mutant for dwarfism. Heterozygotes are recessive lethal mutations causing death, heterozygotes have dwarfism.

Yellow coat colour in mice

Sickle cell disease

Question 15

Explain achondroplasia

Answer 15

Dwarfism due to premature transition of cartiliage to bone.

Question 16

Give examples of recessive lethal mutationa

Answer 16

Yellow gene in mice (individuals homozygous for dominant yellow gene die)
Achondroplasia (individuals homozygous for dwarf gene will die)

Question 17

Albinism is an example of ?

Answer 17

Recessive epistasis.

Question 18

Give the genotype for individuals with albinism

Answer 18

cc

Recessive epistatic mutation. cc masks the effect of all other coat colour controlling genes.

Question 19

Which allele determines the phenotype always in maternal imprinting of the IGF2 gene

Answer 19

The paternal allele will always determine the phenotype because the materanl allele is silenced and not expressed. If the paternal allele is dominant, the phenotype is normal. If the paternal allele is recessive, the phenotype is dwarf!!!

Question 20

Why is the albino c allele epistatic to all other coat colour genes

Answer 20

cc mutants prevent melanin synthesis due to mutations in the tyrosinase enzyme. Tyrosinase enzyme is required for melanin production. Hence no color can be produced.

Question 21

What type of mutation is the c mutant for coat color. Wild type = C (permits color expression)

Answer 21

This is a loss of function mutation

Question 22

Define variable expressivity

Answer 22

Occurs where all have the same allele/genotype but the effect of that allele can be altered among individuals. Hence, individuals will show a range of phenotypes of varying severity/ signs and syptoms.

Question 23

Give an example of variable expressivity

Answer 23

Variable agouti in mice. This is caused by a transposon in the promoter region. The transposon alters the expression of the Yellow Agouti gene, causing different shades of this color.

Question 24

What is retinitis pigmentosa

Answer 24

Degeneration of retina. This is an example of digenic inheritance

Question 25

Give an example of Incomplete penetrance

Answer 25

The BRACA1 gene for breast cancer. Not all individuals with this genotype will develop breast cancer.

Question 26

Provide explanation for why not all individuals with the BRCA1 gene will develop breast cancer

Answer 26

2 Hit hypothesis aims to explain why. Breast cancer (tumor formation) will only occur due to loss of heterozygosity following a “2nd hit/mutation” to the heterozygote. Therefore, not all individuals with the BRCA1 gene will develop cancer because not all indiviudals will incur a 2nd hit

Question 27

Explain Alfred’ Knudsons 2 hit hypothesis

Answer 27

Attempts to explain incomplete penetrance of certain genes. Explains why tumor formation will only occur following a loss of heterozygosity for the TT gene. TT —> Tt —> tt. Only homozygous recessive individuals will develop tumors, and this requires a 2nd hit/mutation.

Question 28

Name the diseases that Alfred Kundsons 2 hit hypothesis applies too

Answer 28

Breast cancer

Neurofibromatosis I

Question 29

What is meant by the term 2nd hit

Answer 29

2nd hit is a 2nd mutation in the genotype. It is a random mutation that causes loss of heterozygosity and can occur during a persons lifetime

Question 30

Define epigenetics

Answer 30

Defined as an inherited change in gene function without having

Question 31

Explain why recessive, loss of function mutations can sometimes be observed in heterozygotes. Ie, normally required to be rr to show phenotype, but Rr phenotypes will show it.

Answer 31

Due to maternal / or paternal imprinting, where one gene is silenced, and the other is preferentially expressed in the embryo.

Question 32

What is meant by the parent of origin effect

Answer 32

Different outcomes in the phenotype of offpsring due to maternal imprinting.

Question 33

Explain why individuals with a breast cancer susceptibility gene BRCA1 gene may never get breast cancer?

Answer 33

Because they have never encountered a “2nd hit” causing loss of heterozygosity in their tissues, and hence tumors will not form.