L5 - Gene interaction 1: departure from Mendelian ratios

Question 1

Amorphic (null) -

Answer 1

produces no protein at all, or protein product completely lack of function (usually recessive) - eg. CFTR 508 allele

Question 2

Hypomorphic (leaky)

Answer 2

Protein function is reduced either due to less protein made, or product itself displays less activity (usually recessive) - e.g. alleles of the gene encoding Tyrosinase - in the pathway that produces melanin from tyrosine

Question 3

Types of loss of function

Answer 3

Amorphic and hypomorphic

Question 4

Types of gain of function

Answer 4

Hypermorphic, antimorphic, dominant lethal and neomorphic

Question 5

Hypermorphic

Answer 5

Increase in activity, either more protein is made or the protein itself has greater activity (usually dominant) - e.g. Heredity pancreatitis (HP)

Question 6

Antimorphic (dominant negative)

Answer 6

Disturbance in function that interferes with protein encoded by a normal allele (usually applies to situations when a protein operates as a hetero- or homo-multimer) - e.g. Mutations in FBN1 ( lead to truncation of FBN1 protein and causes Marfan syndrome)

Question 7

Dominant lethal

Answer 7

Only see this class of mutant later on inline, since onset of a disease is caused by accumulation of the mutant product - e.g. Huntington’s disease (progressive condition)

Question 8

Huntington’s disease is caused by…

Answer 8

a triplet expansion in the HD locus (>36 CAG), giving a polyglutamine tract in the protein. Leads to aggregation of protein into neurotoxic fibrils
* Heterozygous individual develops HD, because mutant polypeptide will aggregate regardless of presence of wild-type protein

Question 9

Neomorphic

Answer 9

Alters the function of the protein (‘new form’) so usually dominant - e.g. antennapedia in Drosophila - gene mutated so that protein now causes development of legs where eyes should be

Question 10

Incomplete (partial) dominance

Answer 10

results in a ‘blend’ of characteristics

Question 11

Codominance

Answer 11

where the presence of both allele id detected equally - e.g. blood type AB

Question 12

Genetic load

Answer 12

The collection of lethal alleles in the population

Question 13

Inheritance of genes on the X chromosome (X-linkage)

Answer 13

• Will occur most frequently in males (bus they only have one copy of X)
• Cannot be passed from father to son
• All daughters of affected fathers are carriers

Question 14

In X-linkage, if the mom is a carrier and the father is normal,

Answer 14

half of the sons of a carrier will be affected and half of the daughters will be carriers

Question 15

Maternal Inheritance

Answer 15

Mitochondria and chloroplasts contain their own circular genome. These organelles are inherited from teh maternal side of a cross

Question 16

Mitochondrial cytopathy

Answer 16

• number of human diseases are caused by the mutations in mtDNA
• can only be passed on by the mother
• An affected mother will transmit the disorder to all offspring!!
• so affects both sexes!
• • but offspring of affected fathers are normal

Question 17

What is matrilineal?

Answer 17

it does not follow any of the autosomal or sex-linked inheritance patterns as it is only passed down the maternal line

Question 18

Mendelian ratios appear when..

Answer 18

mutations are fully penetrant and show consistent expressivity

Question 19

Discrepancy between phenotype and genotype (give rise to non-mendelian ratio) can arise due to:

Answer 19

1) Incomplete penetrance

2) variable expressivity

Question 20

What is incomplete penetrance?

Answer 20

When the phenotype associated with a genotype FAILS to appear in some cases - e.g. polydactyly: a dominant phenotype, yet only 25-30% of individual who carry the mutant allele develop extra digits

Question 21

What is variable expressivity?

Answer 21

When phenotype varies in the degrees of magnitude - e.g. Individuals with Wardenburg syndrome (autosomal dominant)
- Such an allele is also pleiotropic - i.e. affects more than one character

Question 22

Penetrance and expressivity are controlled by…

Answer 22

1) genotype at other loci

2) environmental factors

Question 23

What can be inherited in matrilineal fashion only?

Answer 23

Mitochondrial and plastid DNA

Question 24

What does epistasis mean?

Answer 24

Most phenotypes are controlled by various genes interacting with each other. Epistasis modifies Mendelian ratios!

Question 25

What are the examples of epistasis?

Answer 25

1) Complementary gene action
2) Recessive epistasis
3) Dominant epistasis
4) Duplicate gene action

Question 26

What is Complementary gene action?

Answer 26

• When genes act in tandem to produce a phenotype

- Homozygous recessive genotype at either locus produces the same phenotype

Question 27

What is the phenotype ratio for complementary gene action relationship?

Answer 27

9:7

Question 28

What is Recessive epistasis?

Answer 28

Occurs when A-bb and aabb individuals have the same phenotype (one locus, when recessive, affects the other gene - but not the other way round)

Question 29

What is the phenotype ratio for recessive epistasis relationship?

Answer 29

9:3:4

Question 30

What is Dominant epistasis?

Answer 30

A dominant allele of one gene masks the effect of the genotype at another locus
- A-B- displays the same phenotype as aaB-. Dominant B is epistatic to A

Question 31

What is the phenotype ratio for dominant epistasis relationship?

Answer 31

12:3:1

Question 32

What is duplicate gene action?

Answer 32

Occurs when both genes perform the same function

Question 33

What is the phenotype ratio for duplicate gene action?

Answer 33

15:1