Lecture 11 Way Beyond Mendel Flashcards
Define Epistasis
Epistasis occurs when one gene masks the effects of another gene.
How does dominant epistasis alter the F2 phenotypic ratio
12:3:1 ratio
How does recessive epistasis alter the F2 phenotypic ratio
9:4:3 ratio
Define Pleiotropy
Occurs when a single gene controls multiple phenotypes.
Give two reasons why not all individuals with the same genotype would express the same phenotype
1) incomplete penetrance
2) Variable expressivity
List the two factors responsible for varying phenotypic expression between individuals of a population
- Penetrance
- Expressivity
Define Penetrance
Penetrance is a measure of the percentage of individuals of a csertain genotype express the phenotype
Define Expressivity
Expressivity is a measure of
Explain what is meant by genomic imprinting
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.
Define Maternal imprinting
- The maternal allele is imprinted via addition of an epigenetic tag
- Maternal allele is silenced
- The paternal allele is preferentially expressed in the phenotype.
Define Paternal imprinting
- The paternal allele is imprinted via addition of an epigenetic tag
- Paternal allele silenced
- Only the maternal allele is preferentially expressed in the embryo.
Give an example of a maternally imprinted/silenced gene
The insulin growth factor 2 gene
Give an example of Maternal imprinting
- 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
Give examples of pleiotropies
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
Explain achondroplasia
Dwarfism due to premature transition of cartiliage to bone.
Give examples of recessive lethal mutationa
Yellow gene in mice (individuals homozygous for dominant yellow gene die)
Achondroplasia (individuals homozygous for dwarf gene will die)
Albinism is an example of ?
Recessive epistasis.
Give the genotype for individuals with albinism
cc
Recessive epistatic mutation. cc masks the effect of all other coat colour controlling genes.
Which allele determines the phenotype always in maternal imprinting of the IGF2 gene
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!!!
Why is the albino c allele epistatic to all other coat colour genes
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.
What type of mutation is the c mutant for coat color. Wild type = C (permits color expression)
This is a loss of function mutation
Define variable expressivity
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.
Give an example of variable expressivity
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.
What is retinitis pigmentosa
Degeneration of retina. This is an example of digenic inheritance
Give an example of Incomplete penetrance
The BRACA1 gene for breast cancer. Not all individuals with this genotype will develop breast cancer.
Provide explanation for why not all individuals with the BRCA1 gene will develop breast cancer
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
Explain Alfred’ Knudsons 2 hit hypothesis
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.
Name the diseases that Alfred Kundsons 2 hit hypothesis applies too
Breast cancer
Neurofibromatosis I
What is meant by the term 2nd hit
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
Define epigenetics
Defined as an inherited change in gene function without having
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.
Due to maternal / or paternal imprinting, where one gene is silenced, and the other is preferentially expressed in the embryo.
What is meant by the parent of origin effect
Different outcomes in the phenotype of offpsring due to maternal imprinting.
Explain why individuals with a breast cancer susceptibility gene BRCA1 gene may never get breast cancer?
Because they have never encountered a “2nd hit” causing loss of heterozygosity in their tissues, and hence tumors will not form.
