BIOL 2500 - Topic 5

Variantions on dominance

Roughly 90% of traits do not follow typical Medelian patterns

Looking at traits that don’t follow the typical Mendelian pattern

1.) Can look at interactions between the alleles of a single gene

2.) Can look at the interactions between two or more genes

Mendel’s traits exhibit...

Complete dominance

Complete dominance

It is when the dominant allele completely masks the phenotypic expression of the recessive allele, which is why we see the dominant phenotype

F1 and F2 of complete dominance

F1 - All exhibit the dominant phenotype

F2 - 3:1 phenotypic ratio

Is the recessive allele still being expressed in heterygotes?

Yes, but the presence of the dominant allele masks its effects

How does complete dominance work (at the molecular model)

1.) The mutation in the gene for the recessive allele causes the protein to be non-functional, therefore in the presence of the dominant allele, its effects are masked

2.) The only time the effects of the non-functional recessive allele is shown is when it is homozygous recessive

Haplosufficient

It is when only one copy of the allele is needed to produce enough product (seen in complete dominance)

Haplosufficiency in complete dominance

1.) It is why the WT can be seen in heterozygotes, as only one copy of the allele is needed for it to be functional

2.) And it is why the WT cannot be seen in homozygous recessive, since it has no copies of the allele for it to be functional

Dominant mutations

Mutations that causes a change in the WT, therefore causing heterozygotes to become haploinsufficient

Null mutations

Produces a non-functional protein

Dominant negative

A protein is produced that inhibits the WT protein `

Complete dominance are really _________ of a phenotypic continuum

Extremes

Incomplete dominance

1.) It has two extreme phenotypic ends

2.) And then phenotypes that fall between the two extremes, like they are blending

F1 generation of incomplete dominance

It produces offspring that do not exhibit the dominant phenotype and instead produces the blended phenotype

F2 phenotypic and genotypic ratio of incomplete dominance

1:2:1 (for both the phenotypic and genotypic ratio)

Incomplete dominance in humans

We tend to not see incomplete dominance in humans, as many of our genes are the result of multiple genes (polygenic) or allelic interactions

Simplified examples of incomplete dominance in humans

1.) Dark colouration of eye

2.) Height

3.) Wavy hair

4.) Tay-Sachs disease

Tay-Sachs disease (autosomal recessive)

It cannot break down lipids due to missing/reduced enzyme activity, resulting in lipid build up in the brain and nervous system

Tay-Sachs disease (incomplete dominance)

Homozygous D: normal

Heterozygote: some dysfunction in the enzyme

Homozygous R: complete lack of enzyme

Codominance

Unlike in incomplete dominance where the 2 extremes are blended, in codominance, both the extreme phenotypes are expressed (without blending)

Codominance is usually seen in…

The production of proteins

Codominance examples

1.) ABO blood system

2.) MN blood system

3.) Cows

ABO blood system complete dominance

1.) A and B have complete dominance over O

2.) A and B have codominance

3.) This results in 4 phenotypes and 6 genotypes

How is your blood-type identified?

It is identified by specific antigen-antibody reactions on a microscope slide

How is your blood-type identified? (process)

1.) Place a drop of blood in anti-A and anti-B antiserum wells, which contains antibodies that recognizes carbohydrate structures on the surface of RBCs

2.) If the antibody binds to the antigen protein, it causes the RBCs to clump, indicating a positive result for the blood type

A blood type

Has the A antigen and B antibodies, therefore can only take in A or O, no B

B blood type

Has the B antigen and A antibodies, therefore it can only take in B or O, no A

AB blood types

1.) Have the antigens for both A and B, but no antibodies, therefore it can have A, B, AB, or O

2.) It is the universal recipient

O blood type

1.) It has has no A or B antigens, but it has antibodies for both, therefore it can only take in O

2.) It is the universal donor

Blood donations

The person receiving it must not contain an antibody that reacts with the donations antigens, otherwise it can cause blood clots

MN blood type system

Has M and N alleles that are also codominant, resulting in three different blood types (M, N, and MN)

MN vs. ABO blood systems

They assort independently from one another, therefore we can use separate monohybrids or a dihybrid cross to see what the genotypes of the children may be

Allelic series

It is when multiple alleles within the population are present (prime example being ABO blood types)

Dominance in allelic series

The order of dominance in the various alleles is based on the amount of protein produced when the gene is expressed

Can complete dominance, codominance, and incomplete dominance occur in allelic series?

Yes

Number of genotypes for allelic series

n(n+1)/2

Number of homozygotes in allelic series

n

Number of heterozygotes in allelic series

n(n-1)/2

C-gene system for mammalian coat colour

Polygenic with multiple alleles

C-gene allelic series dominance

C > C^ch > C^h > c

C coat colour

It is the dominant WT colour

C^ch coat colour

1.) Homozygotes produces a chindilla phenotype

2.) It has a reduced coat colour, due to reduced production of tyrosine

C^h coat colour

1.) Produces a himalayan phenotype

2.) The resulting protein is temperature sensitive, such that it works better at cool temps, therefore more pigment is produced away from the core and towards the extremeties

c coat colour

Homozygotes produces an albino phenotype due to the lack of enzymatic activity (i.e. null mutation)

Pure breeding chinchilla x himalayan (C^ch x C^h)

1.) They are codominant to each other, such that heterozygotes have a chinchilla body core but then himalayan extremities

2.) Therefore resulting in a 1:2:1 ratio

Lethal alleles

Mutations in essential genes that causes death if it is homozygous

Recessive lethal alleles

They are rare, as they are usually hidden by the dominant phenotypes as carriers, which is what allows them to persist for long periods of time

Detection of lethal alleles in animals

It is detected due to a distortion in Mendelian segregation proportions, such that you expect a 3:1 ratio, but instead see 100% of the dominant phenotype or a 2:1 ratio

Detection of lethal alleles in plants

It is detected due to embryos dying or gametophytic lethals that fail to produce gametes

Lethal allele example

1.) The agouti gene, which are essential in mice

2.) It is lethal because there is a deletion in the gene that is needed for embryonic development

Agouti gene F1 and F2

1.) F1: if you cross a homozygous WT brown mouse with a yellow mouse, we get a 1:1 ratio (AA:AA^Y)

2.) F2: if you cross two yellow mice, you get a 2:1 phenotypic ratio, rather than 3:1 (because the homozygous yellow is lethal)

Lethal alleles in humans

1.) Tay-Sachs disease

2.) Huntington’s disease

Huntington disease

1.) A neuromuscular disorder, caused by a mutation on the end of chromosome 4

2.) It is lethal in homozygous dominant and heterozygous genotypes

Huntington’s disease symptoms

It has delayed age onset, such that the symptoms are not seen until adulthood, therefore the affected individuals still have a chance to reproduce and pass on the trait to their offspring

Complete penetrance

The genotype always produces the same phenotype, therefore, an organism carrying the dominant allele will always produce the dominant phenotype

Mendel’s traits have ________ penentrance

Complete

Incomplete penetrance

1.) Phenotypic variation is observed, such that the same genotype does not always produce the same phenotype

2.) This is usually due to the environment or other genetic influences

Penetrance

The percentage of individuals with a given allele that exhibits the phenotype that is associated with that allele

Variable expressivity

The same genotype produces variable phenotypes, due to varying expression of the alleles (i.e. expect purple but it does not express the full amount of purple)

Incomplete penetrance example

Polydactyly (extra fingers), an autosomal dominant allele with incomplete penetrance

Variable expressivity example

Piebald spotting in beagles, such that the brown shows varying degrees of intensity in fur colour

Gene-environment interactions

1.) Sex

2.) Age

3.) Temperature

4.) Chemicals and diet

5.) Pathogens and exposure

6.) Pleiotropy

Sex (environmental effect on gene expression)

I.e. sex-limited and sex-influenced traits, as a result of hormone levels

Age (environmental effect on gene expression)

It influences cell functioning, such as telomere shortening, Huntington’s disease, etc

Temperature (environmental effect on gene expression)

Certain enzymes are sensitive to temperatures, resulting in reduced function if not at an optimal temp, such as Himalayan rabbits

Chemicals and diets (environmental effect on gene expression)

Certain diets and exposure to specific chemicals can influence certain traits/conditions, such as PKU and human height

PKU

A defective metabolism due to the lack of breakdown of phenylalanine, causing it to build up and affect mental functioning, but it can be managed by diet

Pathogens and parasites (environmental effect on gene expression)

1.) It can affect the development of allergies

2.) It can create an educated immune system in young children, as a result of early exposure

Pleiotropy

When a single mutation in the genotype alters multiple features in the phenotype

Is pleiotropy the same as variable expressivity

No because variable expressivity involves one trait, while pleiotropy involves multiple traits

Pleiotropy example

Sickle cell disease, where a mutation in the B-globin gene affects the RBC shape, which decreases iron and oxygen intake, among other things

Family studies

It tracks the precedence and prevalence of traits within a family

Family studies on asthama

There is more of a chance of having asthma if one or both of your parents have it, but it is not guaranteed for you to have it if they do

Twins on allergies

Identical (monozygotic) twins are more likely to share allergies than non-identical (dizygotic) twins

Immune system mutations

Mutations in T-helper cells increases allergy risk

Identical twins having the same allergy

They may be allergic to the same thing, but they will most likely display different symptoms (i.e. rash vs. anaphylactic shock)

Incidence of allergies are higher in…

1.) Developed countries

2.) First born kids

Incidence of allergies are lower in…

1.) Large families

2.) Kids attending daycares

3.) Kids from rural families

Hygiene hypothesis

The theory that exposure to more diseases leads to a better immune system

Why are allergies so common?

1.) Allergies are hypothesized to reflect immune systems that have not been exposed to the allergen, combined with the effects of past selection for parasite resistance

2.) Some also believe that it is inherited

Resistance to parasitic worms

It causes huge health problems in developing countries, but resistance increases with age, as the immune system matures and learns to recognize the parasite

Alleles regarding parasitic worms

1.) In rural China and Mali, specific alleles are associated with decreased parasitic worm load

2.) However, in British populations, the same alleles increase susceptibility to allergies

Epidemiological risks for food allergy (pattern)

Patterns support the idea that undereducated immune systems are more likely to develop allergies

Current Canadian guidelines

For the first six months, it is required for mothers to only breastfeed or use formula to feed the baby

How have Canadian guidelines changed?

1.) There are no more restrictions to what the mother can eat during pregnancy and breastfeeding, as they were instructed to avoid it before

2.) Allergenic foods can be introduced to the baby after six months, but it used to be 3 years.

What influences phenotypes

1.) The genotype

2.) Environmental influences and other random events

2.) Actions of other genes and their products (i.e. genetic interactions)

Who came up with the one-gene-one-polypeptide hypothesis

Beadle and Tatum, using forward genetics to investigate the biosynthetic pathways of the Neurospora crassa fungi

Why did they use Neurospora crassa?

1.) Fast growing

2.) Haploid

3.) Can show various phenotypes depending on the medium

How did Beadle and Tatum’s experiment work?

1.) They generated single-gene mutants to infer the function of the genes, by observing how the mutation affected the phenotype

2.) They would observe that the fungus couldn’t grow on certain media due to the change in the enzyme function from the mutation

Results of Beadle and Tatum’s experiment

They found that one gene produces a single enzyme, which has a specialized functional role in metabolism

Prototrophic/prototroph

Refers to the wildtype

Auxotrophic/auxotroph

“Auxo” means lacking, which refers to the mutant

How did they identify auxotrophs?

If the N. crassa could not grow on a certain medium, this meant that they lack the gene to be able to metabolize it

What we know about genes now

1.) Certain genes can produce multiple proteins, via alternative splicing

2.) Some genes produce various RNAs

3.) Others produce peptides that will make quarternary proteins

Beadle and Tatums experiment process

1.) They irradiated the WT neurospora to create mutations

2.) They then transferred the irradiated fungus to a growth medium with everything in it

3.) Then, they transferred the fungi to a minimal medium, that basically had only agar and water

Why did they transfer the fungi from the vitamin-rich medium to the minimal medium?

1.) To identify the prototrophs and auxotrophs.

2.) Those that could grow in means they had all the genes required to grow on the media (i.e. prototrophs)

3.) Those that could not grow means they are lacking the genes that makes the nutrients they cannot get from the medium

What did they do with the auxotrophs that could not grow on the minimal media?

1.) They transferred the auxotroph to various supplemented media to see what it could and could not grow on (i.e. minimal media + AA or vitamins, etc)

2.) If it grew then, then it meant that the auxotroph was missing the gene to make that specific nutrient (i.e. AA or vitamins, etc)

How do they find the exact nutrient that the Auxotroph needs?

They can do a secondary transfer, where they grow them on supplemented media that has only one specific amino acid, or vitamin, or nucleic acid, etc and the one it grows on is the one it was missing a gene for

How to identify gene interactions in a particular phenotype

1.) Obtain single-gene mutants and test for dominance

2.) Test the mutants for allelism (i.e. are they at one or more loci)

3.) Combine mutants into pairs to form double mutants, to see if the genes interact