Incomplete Dominance and Lethal Alleles

BIOL 239: Modifications of Mendelian Ratios - Textbook Sections 2.1-2.3, 4.4

• This week's material will provide an overview of the course structure, evaluations, then delves into Mendelian genetics and their modifications.
• Online learning activities and SmartBook bonus are not the same thing.
• Lecture recordings are not guaranteed to be available or of good quality.
• Review specific things missed the first time if needed.
• It is not recommended to listen to lectures over and over again; instead, review specific topics when required.
• Mendel's experiments looked at traits that each have only 2 variations
• Mendel's experiments dealt with simple dominant-recessive alleles but most traits are more complex
• The topics to be covered this week will be multiple alleles, co-dominance, incomplete dominance, pleiotropy, lethal alleles, additive genes, epistasis, and complex traits.
• The lesson-level learning objectives include explaining the terms, determining phenotypic ratios, identifying inheritance patterns, selecting breeding experiments, defining key terms and explaining ABO blood type inheritance.

Multiple Alleles

• There can be more than 2 alleles for any one gene
• When dealing with multiple alleles, the wild-type allele is designated with a superscript A+.
• Reciprocal crosses can be conducted between pure-breeding lines representing all phenotypes, to establish the dominance relationships between all possible pairs of alleles.
• This reveals a dominance series, in which alleles are listed in order from dominant to recessive.
• The gene for coat color in rabbits is a monomorphic gene
• There is only 1 wildtype allele
• Breeds are selectively bred for rare mutant alleles
• The coat pattern in rabbits has a dominance series, with four alleles: C+ (wild-type), cch (chinchilla), ch (Himalayan), and c (albino).

ABO Blood Types

• The Gene I encodes enzyme that adds terminal sugar onto polymer chain.
• The allele IA adds "A" sugar.
• The allele IB adds "B" sugar.
• The allele i adds nothing
• The gene is polymorphic with 3 common alleles
• IA and IB are each dominant over i.
• Both IA and IB are codominant to each other.
• Phenotypes:
  • IAIA or IAi = "A" sugar, type A
  • IBIB or IBi = "B" sugar, type B
  • IAIB = both "A" and "B", type AB
  • ii = none, type O
• Blood Type A has antibodies against B in serum
• Blood Type B has antibodies against A in serum
• Blood Type AB has no antibodies against A or B in serum
• Blood Type O has antibodies against A and B in serum
• Gene H controls production of the polymer to which the A and B sugar attach
• The h Bombay allele in blood type is epistatic to gene I.
• The H/h controls production of lipid H to which A and B sugars are attached.
• The hh is always type O, no matter what I/i is.
• It's possible for 2 type O parents to have a type A child if mother is IA_hh (she has IA allele but it does not express).

Co-dominance

• Contributions from both alleles are visible in the phenotype
• The genotype and phenotype ratio mirror each other, showing the same 1:2:1
• Neither allele is dominant or recessive to the other.
• Alternative traits are both visible in the F₁ hybrid

Incomplete Dominance

• The heterozygote has an intermediate phenotype
• The F₁ hybrid resembles neither purebred parent and has an intermediate phenotype.
• Demonstrated by the snapdragon flower, where a red (AA) and white flower (aa) cross to produce pink offspring (Aa).
• Genotype and phenotype ratio is 1:2:1.
• Now that it is known that the alleles are incompletely dominant, they can be re-designated to reflect this.
• The alleles can be shown as A1A2 or RrRw
• It is proper to designate incompletely dominant or co-dominant alleles as both uppercase.
• Testcrosses are unnecessary to determine the genotype as the genotype can be directly "seen."
• One "dose" of the red pigment results in an intermediate pink offspring that do not resemble either of their parents.

Pleiotropy

• One gene influences multiple traits
• Multiple phenotypic effects caused by a single gene
• Examples include sickle cell syndrome.
• Sickle sell anemia is caused by a single nucleotide mutation in the HBB gene
• HBB gene encodes B-globin
• Adenine -> thymine sub changes 6th codon of mature protein from glutamine to valine
• HbSS causes molecules to polymerize

Lethal Alleles

• A dominant or recessive allele that can kill the organism
• Agouti allele (wildtype) = A (A+)
• A produces bands of yellow and black on each hair
• Yellow allele = AY
• AY prevents deposition of black; hairs are yellow
• Yellow mice are always heterozygous
• The AyAy is a lethal combination, so yellow mice are always heterozygous.
• The phenotypic ratio of offspring from heterozygous parents is always 2:1, not 3:1; the homozygous AYAY die.
• Allele for yellow coat is dominant for coat colour but recessive for lethality (recessive lethal allele).
• Two heterozygotes for A+ and yellow (AY) produce only yellow and agouti offspring in 2:1 ratio.
• Manx cats - spinal development, homozygous fetus dies in utero.
• All Manx cats are heterozygous for the Manx allele.
• Manx allele is dominant for taillessness and recessive for lethality (recessive lethal allele).
• It is possible for one allele to affect 2 different phenotypes (pleiotropy)
• Dominance for one phenotype does not mean it has to also be dominant for the others
• The wildtype allele isn't always dominant.

Additive Genes

• Two or more genes influence one trait

Epistasis

• One gene hides the effect of another gene
• Dominant epistasis is shown in Summer squash colour example.
• 12:3:1 phenotypic ratio signifies dominant epistasis
• C_ = white
• cc = yellow or green
• C (no colour) masks G (yellow) and gg (green)
• Allele C is epistatic to gene G
• Recessive epistasis is illustrated by coat color in Labrador retrievers.
• Phenotypic ratio 9:3:4 indicates recessive epistasis
• B_ = black
• bb = brown
• E_ = expression of gene B; E_ must be present for color.
• ee = no expression of gene B
• The ee is epistatic to gene B.
• Dogs with genotype ee appears yellow no matter what B/b is, and typically has pale eyes and nose.

Epistasis in Blood Types

• Gene H controls production of the polymer to which the A and B sugar attach
• recessive epistasis is in h Bombay allele in blood type
• H/h controls production of lipid H to which A and B sugars are attached
• hh is always type O, no matter what l/i is. This can be used as example of complementary gene action.
• Phenotypic ratio of I^iHh x I^iHh is 9:7 type A type to O
• At a molecular level, there is not just one product being produced; there are 2 different products that are not working in a metabolic pathway.
• The textbook calls this complementation "reciprocal recessive epistasis".

Complementary Gene Action

• Complementary gene action occurs when two or more genes work in tandem in the same biochemical pathway to produce a particular trait.
• It is responsible for a heterogenous trait
• Results in a phenotypic ratio of 9:7.
• Used in complementation testing to see if 2 individuals have mutations in the same gene

Complex Traits

• A trait determined by many genes or by interaction between genes and environment.
• Novel phenotypes can emerge from the combined action of the alleles of two genes - e.g., comb shape in chickens.
• The phenotypic ratio of 9:3:3:1 is indicative of 2 genes independently responsible for comb shape.
• Multifactorial inheritance is a phenotype that is affected by the action of two or more genes, and by interactions with the environment.

Penetrance and Expressivity

• Penetrance signifies the percentage of the population with a specified genotype who exhibit the expected trait.
• Expressivity is the degree or intensity with which a particular genotype is expressed in a phenotype within a population.
• A high degree of unpredictability in phenotype expression exists.
• Factors such as influence of environment, modifier genes, and chance. Retinoblastoma, a dominant allele, not all persons carrying the allele exhibit disease.

Sex-Linked, Sex-Limited, and Sex-Influenced Traits

• Sex-linked traits are due to genes ON the X or Y chromosome (e.g., hemophilia and color blindness).
• Sex-limited traits affect a structure or process found in only one sex like bright plumage in male birds/milk production.
• Sex-influenced traits show up in both sexes
• Sex-influenced trait examples are patterned baldness
• Sex-influenced traits their expression may differ between the sexes and are caused by genes that are not on sex chromosomes
• Androgenetic alopecia (male patterned baldness) is a sex influenced trait
  • loss of hair from forehead and crown
  • affects ~70% of men, but not women
  • this trait is highly heritable
  • there are multiple autosomal and Chromosome x genes associated with this trait

Environmental Influences

• Factors such as temperature, light, and altitude can affect the phenotypic expression of a genotype.
• The environment can affect the phenotypic expression of a genotype (e.g., Himalayan coat pattern in cats/rabbits).
• Conditional lethality is when an allele is lethal under only certain conditions (permissive vs. restrictive conditions).

Deciding Between Hypotheses

• Truebreeding: white x brown: New phenotype of F₁ progeny can indicate more than 1 gene is involved, or incomplete dominance of alleles in 1 gene.
• Ratio can indicate recessive epistasis.
• Answering the question: "What's the actual genotype of an F2 white mouse?"
  • To solve for B, do a test cross.

Examples of problem solving

• A pure-breeding white goat and a pure-breeding black goat are bred together several times and all offspring are grey, this is an example of incomplete dominance
• Coloration with 1:2:1 ratio could be indicative of Co-dominance or incomplete dominance
• You don't always get the expected ratios if there are small numbers of offspring
• Average cow can only produce 8 offspring in its life
• To determine "what is the mode of inheritance of coat colour", and grey cow is bred with grey cow, but they produce new white and black phenotypes.
• This could be indicative of incomplete dominance,
• It is seen a white fur phenotype from 2 greys the coloring type is codominance because it's 1:2:1

Explore incomplete dominance, where heterozygotes display intermediate phenotypes, eliminating the need for test crosses. Investigate pleiotropy, where single genes influence multiple traits, using sickle cell anemia as an example. Learn about lethal alleles and their impact on offspring ratios.