Extensions of Mendel's Principles

Alleles

variants of one gene; changes in DNA —> changes to protein structure

Types of dominance

1) Complete dominance

2) Incomplete dominance

3) Codominance

Complete dominance

One allele determines phenotype

• Trait is completely determined by dominant allele

• Recessive allele is “hidden”

  • May be lack of trait (red vs white flower)

• One dominant allele is enough to produce the full phenotype (protein)

What does the complete dominance chart show?

The bars show amount of protein produced:

• AA → high protein level

• Aa → medium protein level

• aa → very little or no protein

The red dashed line = threshold needed to show the trait

If the amount of protein is above the threshold, the dominant trait appears.

Even though Aa makes less protein than AA,
it still makes enough to cross the threshold.

That’s why:
👉 One copy is sufficient
👉 The dominant allele “wins”

Example: Flower Color

• A allele makes red pigment

• a allele makes no pigment

Genotypes:

• AA → lots of pigment → red

• Aa → enough pigment → red

• aa → no pigment → white

Modifications to complete dominance

“Modifications” = situations where heterozygote (Aa) does NOT behavior exactly like AA (simple dominant-recessive model doesn’t fully apply)

1) Haploinsufficiency

2) Dominant negative

Haploinsufficiency

A genetic condition where one functional copy of a gene is insufficient to produce enough protein for normal function, resulting in a disease phenotype

• Cannot produce enough protein in heterozygote

AA = normal

Aa = abnormal

aa = more severe abnormal

Dominant negative

Mutated allele is dominant and “overwhelms” wild-type

• The mutant protein interferes with the normal protein’s function, causing disease even when one normal allele is present

Example: Marfan syndrome (FBN1)

Incomplete dominance

Both alleles determine phenotype

• The heterozygote is intermediate/blend between the two homozygotes

Flower example

AA = red

aa = white

Aa = pink

Why pink? Because AA produces a lot of red pigment, aa produces none, and Aa produces half the pigment = intermediate color - pink = blend between the two homozygotes

Codominance

Both alleles determine phenotype (are fully and separately expressed); heterozygote shows BOTH traits at the same time

• Heterozygous express both traits

• Example: AB blood groups: express both A and B antigens; not blended or intermediate, but both fully present

Multi-allelic traits

Multiple alleles for a gene present in a population (a gene has more than 2 possible alleles)

• A wider assortment of genotype possible

• Individuals still have two alleles at a time

• Alleles are different mutations in the same gene

REMEMBER: each individual still only has TWO alleles (diploid) but the population can have many versions

Instead of just A and a, there might be A, a¹, a², a³, etc.

Dominance series

For multi-allelic traits (multiple alleles for a gene present in a population)

Example: rabbit coat color

If two alleles are paired, the higher one in the hierarchy determines phenotype.

Full color (C) > Chincilla (Cch) > Himalayan (Ch) > Albino (Ca)

Partial penetrance

Phenotype does not express 100% of genotype

• Environment, timing, other alleles can shift threshold

• Observed individuals are less than expected

Even if someone has a genotype that “should” cause the trait: They might not express it if protein levels do not cross the threshold.

Ex. BRCA1 mutation (breast cancer): inherited gene in autosomal dominant manner, but not everyone with the mutation develops cancer

What does this graph for partial penetrance show?

Even if someone has a genotype that “should” cause the trait: They might not express it if protein levels do not cross the threshold.

Example of partial penetrance

Example: Waardenburg Syndrome - Dominant allele but low penetrance

• 45% of WS1/WS1 or WS1/ws1 individuals develop symptoms

Expressivity

Degree of phenotype varies with same genotype

Example: Polydactyly

• Extra digits on one or more hands or feets

• Digits of varying length and development

• Even if two people both have polydactyly, it may express differently; one individual might have very long hands while the other very long feet

Partial penetrance vs. expressivity

Partial (Incomplete) Penetrance - does the phenotype appear at all? not everyone with the genotype shows the trait

Expressivity - how strongly is the phenotype expressed? everyone with the genotype shows the trait, but severity differs

Pleiotropy

One gene affects many traits

Example: Waardenburg Syndrome

• One gene: affects heating, vision, skin color, hair color, etc.

Environmental effects

Gene-by-environment interactions

• Individuals can have the same genotype, but show different phenotypes depending on the environment

• Example: temperature sensitive alleles

  • Himalayan rabbits: Heat disrupts protein structures, so higher temps result in white color, while lower temps result in normal black and white color

These rabbits have a pigment gene that only works when it’s cool.

• In cold temperatures (≤ 20°C):
  The enzyme works → pigment is made → dark fur.

• In warm temperatures (> 30°C):
  The enzyme doesn’t work → no pigment → white fur.

Multi-gene traits

Multiple genes influence the same trait

• Traits can be complex

• Assemblage of structures with different proteins

• Different proteins acting at different times in development

Multi-gene traits scenarios

1) Complementation

2) Epistasis

Complementation

Type of multi-gene trait

• Mutations in DIFFERENT genes = same trait (Two individuals have the same mutant phenotype, but the mutations are in different genes.)

• When crossed, heterozygous offspring return to wild-type (normal)

Complementation = restoration of wild-type phenotype when two recessive mutations in different genes are combined in a heterozygote.

Why does crossing two individuals with the same mutant phenotype but mutations in different genes lead to the normal (wild-type)?

Each parent has:

• One defective gene

• But a normal copy of the other gene

When crossed:
The offspring get one working copy of BOTH genes.

So the normal function is restored.

Guinea pig example of complementation

Two hairless guinea pigs due to mutations in different genes

• Skinny pig - genotype: hr/hr || B+/B+ (mutation in hr gene, normal B gene); hairless because hr gene is defective

• Baldwin - genotype: HR+/HR+; b/b (normal hr gene, mutation in b gene); also hairless, but because b gene is defective

When we cross them, the offspring become hr+/hr || B+/b

Each baby now has one working copy of hr, and one working copy of b, so the F1 offspring have fur (wild-type)

Epistasis

Type of multi-gene trait

• One gene masks the effects of another

• Example: coat color in dogs

  • Gene B: B = black pigment; b = brown pigment

  • Gene E: E = allows pigment deposition; e = no pigment deposited

If genotype is ee → no pigment → yellow dog, even if B is present (for black pigment).

• Gene E controls whether B can show its effect.

• E is epistatic to B (E gene masks the effect of B gene).

Phenotypic ratio changes

Normally dihybrid cross gives 9:3:3:1.

But here:

You get:

9 black
3 brown
4 yellow

That 4 yellow group includes:

• B_ ee

• bb ee

Both yellow because ee masks B locus.

So you see 9:3:4 ratio.

Polygenic traits

Continuous traits

• “Additive genetic variation” - effects of different alleles add up to influence the trait

• Coded by genes at many loci

• Examples: height, skin, color in humans