Genetics Notes

End of Chapter 4

Mendelian Genetics as a Baseline

• Mendel's research serves as the foundation for understanding inheritance.

• Deviations from Mendelian genetics are explained in relation to his principles.

Gene Interactions

• Phenotypes are often controlled by multiple genes, with genes interacting with each other.

• A single gene can influence the expression of other genes.

Epistasis

• Definition: The expression of one gene modifies the phenotype of another.

• Can mask or alter the expected phenotype.

• Conceptual difficulty arises in determining which gene is epistatic.

Examples of Phenotype Control

• Eye color and skin color are usually the products of multiple proteins.

• Pigment biosynthesis often involves a series of enzymes.

• A signal transduction pathway (series of enzymatic reactions) leads to a final product (phenotype).

Biochemical Pathways

• Genetic traits are the final products of signal transduction pathways.

• These pathways involve starting materials, enzymes, and intermediates.

Example Pathway

1. Starting materiaAL

2. Enzyme 1 modifies it into Intermediate 1.

3. Enzyme 2 modifies Intermediate 1 into Intermediate 2.

4. Enzyme 3 modifies Intermediate 2 into the final product (phenotype).

• Example: Pigment in a flower that makes it purple.

• Example: Bioluminescent molecule in bacteria within light organs of fish.

Complexities of Genetic Traits

• Genetic traits are the product of multiple genes involved in a biochemical pathway.

• Deletion of a gene can result in:

  • No pigment at all.

  • A different pigment color.

Protein Level Effects

• Mutations at the protein level influence phenotypes.

• A mutation in one gene can affect the phenotype, making that gene epistatic over others.

Labrador Retrievers: An Epistasis Example

• Coat color in labs is controlled by two genes: B and E.

• Three possible colors: black, chocolate, and yellow.

The B Gene

• The B gene behaves in a Mendelian fashion.

• $B$ (dominant) encodes black coloration.

• $bb$ (homozygous recessive) results in brown coloration.

The E Gene

• The E gene is epistatic to the B gene; it controls whether the B gene matters.

• $ee$ (homozygous recessive) always results in a yellow lab, regardless of the B genotype.

• If at least one $E$ allele is present, the lab will be either black or brown, depending on the B genotype.

• The E gene affects a step prior to the B gene's influence on color.

Protein-Level Explanation

• A functional E enzyme is required to get to black or brown coloration.

• The $ee$ genotype likely produces a non-functional enzyme, preventing the necessary intermediate for the B gene to act.

Epistasis in Labs

• E gene controls or masks the phenotype expected from the B gene.

Deafness: A Multigene Example

• Hearing results from multiple genes.

• Mutations in any of these genes can lead to deafness.

• Each gene is epistatic to the others because the entire system relies on each part.

Explanation

• Ear formation requires many interacting genes.

• Mutations leading to non-functioning gene products result in hereditary deafness.

• Deafness can result from many genes and not just one mutation.

• If there are 25 genes involved in ear formation and one fails, you may result in deafness, making the failed gene epistatic to the other 24.

Bombay Phenotype: Another Epistasis Example

• Individuals phenotypically type O, but can pass on A or B alleles.

• Mother with AB blood type has a daughter with type O, who then has a child with type AB.

• Due to a missing gene (FUT1) needed for the expression of A and B antigens.

The FUT1 Gene

• Encodes a mutase enzyme necessary for presentation of blood type antigens.

• Homozygous recessive condition prevents the expression of A and B antigens.

H Factor Analogy

• FUT1 gene product (H factor) is like a microphone stand; A and B antigens are like microphones.

• Without the stand, the microphones (antigens) cannot be displayed on the cell surface.

Epistasis in Bombay Phenotype

• FUT1 gene is epistatic to blood type genes.

• As long as the H substance is absent, the blood type will appear as type O, despite the actual genotype.

Non-Mendelian Ratios Due to Epistasis

• Epistasis masks or changes phenotypes, leading to non-Mendelian ratios.

• Mendel's dihybrid crosses yielded a 9:3:3:1 ratio.

• Epistasis modifies this ratio (e.g., 9:3:4 or 12:3:1).

  • Genotypes are still inherited 9:3:3:1, but phenotypic expression deviates.

Coat Color in Mice: Recessive Epistasis

• Two genes: B (black pigment) and A (Agouti color).

• $bb$ (homozygous recessive) at the B gene is epistatic over the A gene, resulting in albino mice.

Gene Interactions

• B gene:

  • $B$ - black coloration.

  • $bb$ - no coloration (albino if epistatic).

• A gene:

  • $A$ - Agouti color.

  • $aa$ - no Agouti color.

• In the absence of the Agouti, the mouse is all black whenever there is a dominant $B$ allele present.

• If the B gene is homozygous recessive, then there is no color produced and mice are albino.

Phenotypic Ratios

• Expected genotypic ratio (9:3:3:1) is altered to a 9:3:4 phenotypic ratio.

  • 9 Agouti (at least one dominant allele for both $A$ and $B$).

  • 3 Black (dominant allele for $B$, homozygous recessive for $A$).

  • 4 Albino (homozygous recessive for $B$, masking the $A$ gene).

Summer Squash Fruit Color: Dominant Epistasis

• Dominant allele at one locus masks the alleles at another.

• Only one dominant allele is needed for epistasis, not the homozygous recessive requirement as seen earlier.

Gene Interactions

• A allele:

  • $A$ (dominant) - white fruit (epistatic).

  • $aa$ (homozygous recessive) - B gene matters.

• B gene (when $aa$):

  • $B$ (dominant) - yellow color.

  • $bb$ (homozygous recessive) - green color.

Phenotypic Ratios

• Expected 9:3:3:1 ratio is altered to a 12:3:1 phenotypic ratio.

  • 12 white (any $A$ allele).

  • 3 yellow ($aa$ and at least one $B$ allele).

  • 1 green ($aa$ and $bb$).

• If $A$ has a dominant allele, it doesn't matter what allele is present at the $b$ gene. All the outcomes will be white fruited.

Complementary Gene Interactions

• Genes complement each other; both must be present for a specific phenotype.

• Deletion of either gene results in a different phenotype.

• Enzymes that work together; the absence of either of them would result in there being no final product.

Flower Color in Sweet Peas Example

• Purple flowers require both functional dominant alleles of A and B.

• Absence of either dominant allele results in white flowers.

Simplified Enzymatic Reaction

1. White starting material.

2. Enzyme 1 (from gene A) produces a white intermediate.

3. Enzyme 2 (from gene B) produces a purple final product.

• If both enzyme 1 and 2 are functional, flowers are purple.

• If either enzyme is non-functional, the flower is white.

• If $A$ is homozygous recessive, this protein is nonfunctional, which means that any outcomes will become white flowers.

Phenotypic Ratios

• Produces a 9:7 ratio.

  • 9 purple (at least one dominant allele for both genes).

  • 7 white (homozygous recessive for either or both genes).

Summer Squash Shape: Additive Gene Interaction

• Shapes can be elongated, disc, or round.

• Homozgyous recessive results in elongated, while disc is from flattening the fruit and making it round.

• Interacting phenotypes compress the lung phenotype to be round or shaped as a disc.

Gene Interactions

• Long Phenotype.

• Round Phenotype.

• Disc Phenotype.

Phenotypic Ratios

• Produces a 9:6:1 ratio.

  • 9 disc-shaped (dominant alleles at both A and B loci).

  • 6 spherical/round (one dominant allele at either A or B, but not both).

  • 1 elongated (recessive at both loci).

Learning and Conceptual Takeaways

• It is not as important to memorize the exact ratios.

• Understanding how the genes interact is more important.

• At least one gene is epistatic to the other, or they act in concert to produce the phenotype.

• They are deviations from Mendel's laws of inheritance. The genotypes of the plant is always 9:3:3:1, but the way the phenotype appears can deviate from the expeted outcomes.

• If there is a dihybrid cross or higher. There will always be Non-Mendelian inheritance if these genes interact.

Complementation Analysis

• Determines if two mutations are in the same gene or different genes.

• This can tell you whether the mutant that you observed was in the same gene or not.

Process

• Cross two organisms with the same mutant phenotype.

• If offspring show the wild-type phenotype, the mutations are in different genes (complementation).

• If offspring still show the mutant phenotype, the mutations are likely in the same gene (no complementation).

• Complementation is defined as mutants in a single gene compensating for mutations in another.

Fruit Flies Example

• Two labs produce wingless fruit flies and wish to find out if the mutation occurred in the same gene.

• There are two scenarios whether the mutation occurred in gene 1 or gene 2. The mutations need to be in separate genes for complementation to occur.

Pleiotropy

• One gene affects multiple phenotypes.

• A gene can affect the cells in your muscles, liver, or gallbladder. Expression of the same gene in different forms will cause negative affects and a pleiotropic effect on the organism.

Human Examples

• Marfan syndrome: autosomal dominant mutation in fibrillin gene ( affects eyes, heart, and bone).

• Porphyria variegata: inadequate metabolism of porphyrin.

X-Linkage

• Genes present on the X chromosome can occur when talking about sexes.

• Because if direction crosses in fertilization matters, you can see X linkage in the genome.

• There are not very many phenotypes on the Y chromosome.

• These genes are on the X chromosome, so they only have this gene on the X chromosome and absent on their Y.

• Inheritance is very different in this situation and DOES NOT all Mendelian genetics, especially when talking about genes passed from mother to son

• X and Y differ, creating unique inheritance patterns.

• Studied by Morgan in Drosophila, showing sex-linked inheritance.

Morgan's Experiments

• Reciprocal crosses (red-eyed female x white-eyed male vs. white-eyed female x red-eyed male) did not yield identical results.

• For cross A, expect all red eyed flies to appear under Mendelian genetics. Instead Morgan saw all the females with red eyes and all the males with red eyes

Cross A

• Red-eyed females x white-eyed males:

  • F1 generation: all red-eyed flies.

    • all of the offspring gets a red allele from the mother.

  • F2 generation: 3:1 red:white ratio, but all white-eyed flies were male.

    • Half the flies were female and all of them were red eyed.

    • And just slightly less than half the males had white eyes and half had red eyes.

Cross B

• White-eyed females x red-eyed males:

  • F1 generation: all red-eyed females and all white-eyed males.

    • Females were red eyed because that is the dominant trait. The father gave all the females the dominant trait.

    • Males were not heterozygous, so the presence of the recessive trait will be observable.

  • F2 generation: 1:1:1:1 ratio of red-eyed females: white-eyed females: red-eyed males: white-eyed males.

Chromosomal Explanation

• Focusing on X and Y chromosomes clarifies inheritance patterns.

• Genes on sex chromosomes influence the expression of their inheritance.

• Chromosomes determine that there is no eye color so there is only hemizygous inheritance.

• Linked, so the patterns of inheritance are going to follow a similar fashion.

Important Information from Diagram.

• Unique is a chromosome and all of them have unique paternal and maternal derived outcomes.

• If there is a x chromosome with the mother with a Y, they are hemicozygous

Crisscross Inheritance

• Specific pattern caused by X-linked genes.

• Phenotype traits or color blindness controlled by receive x linked genes can be homozygous with all of the her sons. Her sons would carry the disease and all the traits would disappear from being carriers. The trait reemerges in the mail with the color blindness with each crisscross

• More prevalent in males.

Color Blindness Example

• Red-green color blindness is X-linked.

• If the mother is colorblind. You will pass it to all of her sons.

• She has sons because that is all the Y gene can contribute.

• Daughter may inherit as carriers, some mutations from mother's x chromosomes.
  *

Muscular Dystrophy

• If the genetic disease that had and passed it to the offspring and it would have increased severity from them than you.

• Genetic anticipation

• There is an X inheritance that is lethal. Must go back to a recessive lethal effect. If male is there that will take his life from muscular distopy.

Sex-Limited Inheritance

• Expression of genes only in one sex, not necessarily on the sex chromosomes (but is only expresses in certain males because a certain gene is present).

Gene and Hormone Expression.

• There are sex limited inheritance where hormones and males or females have the same kind of hormones on them.

• Expression depends on hormone constitution of the individual.

• The gene is autosomal or non-sex chromosome, so the the plumage is is present and on on birds. The male has the gene for males but that only gets switched on with the hormone.

• Gene product, feathering that is controlled for recessive allele but it is something that is expressed in mails

Feather chicken plumage.

• There is dominant trait for presence In both sexes.

  Male pattern baldness.

• It is present in more males and the autosomal gene are present and it is the recessive trait to express them in females.

• So if the b is autosomal that means they have more of the genetic trait and it can be more prevalent in males for those other reasons.

Influence from Environments.

• Testosterone depends on environment.

• You can have heat shock when exposed to high temperatures.

• Your environmental genotypes combine together because the environments can control it through gene expression or without

Penetrance and Expressivity

• Not only has the genotype matters . It is how much the proteins you make.

• The phenotype is higher in males, therefore expressed more. EX: Color blindness with higher expression in males!

• range of expression of a mutation phenotype ( Baldness having higher phenotypes and males.

Morgan Fly test. (EYELESS)

• Drosophila with Eyeless mutations!

• Has to do with the levels of penetration and expression.

• Regulatory gene to show activation, the levels of expression would be full and the intermediate eye would be intermediate size.

Temperature conditional mutation.!

• Animals and plants respond depending on temperature for certain traits they will show!

• Primrose show red color on flower if temperature, or certain animals like rabits regulate the hair on certain areas.

• Heat also regulates body weight!

• The more you learn about the environment. The more gnes you keep expressing!

  Genetic expression traits/disease.

• Genes being translated into certain trait.

• Genes for human expressions that happens prenataily.

• Gene might be important as small childhood. But it can change because some genes will only start expressing as a full adult.

Genetic Anticipation

• The genetic disease will express itself will express the most and increasing with the next generation.

• With the genetic disease. The one you passes it to the offspring. More in the grandchildren. Then it get sworse again in the grandchildren.

Extranuclear Inheritance

• Encoded DNA information.

• Can be determined after the cell has been express.

• What really matters is how the expression is shown.

• Pheno and maternal types effect

Inheritance patterns related to Chloroplast/mitochondria.

• There is a non-chromosome. And the organella hereditary can affect the phenotype.

• Inheritance isn't going to affect meosis

• organelles reproduce because the mitochondria will divide. The amount of each mitosis that it has when it is dividing and splitting.

Heteroplasmy

• The level of mutation.

• This might affect the expression of the allele or organelle.

• Can be really important for regulating mutation.