Genetics Exam 2 Material (9/22/25)
Exam One Review
Performance: The class average for Exam One was 78, which is considered good for a genetics first exam.
Release: Exam grades will likely be released today. There are a few minor details to resolve, including some logistical issues due to the instructor's absence during the exam for a family emergency.
Review Session: A Google Form will be sent for scheduling ten-minute individual review slots, allowing students to check basic parts of their exams without waiting in a long line. More thorough analysis can be done in a follow-up session.
Manks Question (Lethal Allele):
This question was removed from the exam and full credit was given to all students, as almost no one answered it correctly. This acted as a bonus 3 points.
Explanation: The question involved a cross between two heterozygous Manks cats that were short-tailed. Manks is a species, and a Manks cat is characterized by a short tail. The genotypic ratio for a heterozygous cross (e.g., Aa imes Aa) is typically 1:2:1 (1 homozygous dominant, 2 heterozygous, 1 homozygous recessive).
However, the homozygous dominant genotype (AA) in Manks cats is a lethal allele, meaning offspring with this genotype do not survive. Therefore, they "do not exist."
The observed genotypic ratio would then be 2:1 for the surviving offspring: 2 heterozygous (Aa) and 1 homozygous recessive (aa). The phenotypic ratio would correspond to this, with two short-tailed (heterozygous) individuals for every one normal-tailed (homozygous recessive) individual. This was a challenging question due to potentially confusing language.
Gene Interactions: Basic Concepts
Definition: Gene interaction refers to how proteins produced by different genes on the same or different chromosomes interact with each other to influence a phenotype.
For example, a gene on chromosome 2 might produce a protein that interacts with another protein made by a gene on chromosome 2 or another chromosome. This interaction is not related to meiosis/mitosis crossing over but to protein function.
Types of Basic Interactions:
Product Synthesis: Genes work together to create a product.
Masking (Epistasis): One gene prevents another gene from expressing its phenotype or performing its function.
Suppression: One gene suppresses the effect of another in a different way.
Example (Color Deposition):
Consider two genes, R (for color, e.g., red/yellow) and C (for color deposition/chlorophyll presence, e.g., green).
If C is dominant, there's no green. If cc (homozygous recessive), green pigment is present.
A typical dihybrid cross (e.g., RrCc imes RrCc) would yield a 9:3:3:1 phenotypic ratio if there's no epistatic interaction.
Illustrative breakdown:
Red: Dominant R and dominant C (no green, red color shows).
Yellow: Recessive rr, but dominant C (no green, so yellow shows).
Green: Recessive rr and recessive cc (green pigment present, masking yellow).
Genes can be on the same chromosome or different chromosomes and still interact.
Epistasis: Masking Gene Effects
Definition: Epistasis occurs when one gene (epistatic gene) masks the effect of another gene (hypostatic gene) at a different genetic locus. This is distinct from regular dominance, where one allele at the same locus masks another allele.
Epistatic Gene: The gene that does the masking.
Hypostatic Gene: The gene whose expression is masked.
Recessive Epistasis (Labrador Retrievers)
Definition: The masking gene must be in its homozygous recessive form to exert its masking effect.
Example: Labrador Coat Color
Genes:
B/b: Determines black (dominant B) or brown (recessive bb) pigment.
E/e: Controls pigment deposition.
Parental Cross (P1): Black (BBEE) $ imes$ Yellow (bbee) $
ightarrow$ All Black (BbEe) in F1 generation.F1 Intercross (BbEe imes BbEe): Expected 9:3:3:1 ratio of genotypes. However, the observed phenotypic ratio is altered to 9:3:4 due to epistasis.
Phenotypes and Genotypes:
Black Labs (9/16): Genotype: Big B, Big E (at least one dominant allele for both genes). For example, BBEe, BbEE, BbEe.
Dominant B gives black, dominant E allows pigment deposition.
Brown Labs (3/16): Genotype: little b, little b, Big E (homozygous recessive for B, at least one dominant E). For example, bbEE, bbEe.
Recessive bb gives brown, dominant E allows pigment deposition.
Yellow Labs (4/16): Genotype: little e, little e (homozygous recessive for E).
The presence of ee prevents the deposition of any dark pigment (black or brown), resulting in a yellow phenotype regardless of the B gene (i.e., masks both B_ and bb).
This includes genotypes like BBEe, BbEe, bbee. They all appear yellow.
Mechanism: The ee genotype effectively blocks the expression of the B gene. The E gene controls pigment deposition.
Ratio: 9 (Black) : 3 (Brown) : 4 (Yellow).
**Genotype breakdown for 9:3:4 Ratio (where *b* (or a) is hypostatic and e (or b) is epistatic):
9/16: Dominant for both genes (e.g., AB)
3/16: Homozygous recessive for the hypostatic gene, dominant for the epistatic gene (e.g., aaB_)
4/16: Homozygous recessive for the epistatic gene, masking the other gene's outcomes (e.g., _ _bb
Dominant Epistasis (Squash Color)
Definition: The masking gene, when in its dominant form, masks the effect of another gene.
Example: Squash Color
Genes:
W/w: Determines white (dominant W) or colored.
Y/y: Determines yellow (dominant Y) or green (recessive yy).
Parental Cross (P1): White (WWYY) $ imes$ Green (wwyy) $
ightarrow$ All White (WwYy) in F1 generation.F1 Intercross (WwYy imes WwYy): Expected 9:3:3:1 ratio of genotypes. The observed phenotypic ratio is 12:3:1.
Phenotypes and Genotypes:
White Squash (12/16): At least one dominant W allele. This W allele masks both yellow and green coloration.
This group includes genotypes like WY (normally would be two dominant traits) and W_yy (normally a dominant W and recessive yy).
Yellow Squash (3/16): Homozygous recessive for w and at least one dominant Y allele (e.g., wwY_).
Green Squash (1/16): Homozygous recessive for both w and y (e.g., wwyy).
Biochemical Mechanism:
A colorless precursor (white) is converted by Enzyme 1 (controlled by gene w) to Compound B (green).
Compound B is converted by Enzyme 2 (controlled by gene y) to Compound C (yellow).
A dominant W allele prevents the action of Enzyme 1, stopping the pathway at the colorless precursor stage, resulting in white squash.
Only with ww (recessive) can Enzyme 1 function to produce green. Then, if Y is present, Enzyme 2 produces yellow. If yy, it remains green.
Ratio: 12 (White) : 3 (Yellow) : 1 (Green).
**Genotype breakdown for 12:3:1 Ratio (where *y* (or b) is hypostatic and w (or a) is epistatic):
12/16: Dominant for the epistatic gene (e.g., A_ B + A_aabb)
3/16: Recessive for the epistatic gene, dominant for the hypostatic gene (e.g., aaB_)
1/16: Recessive for both genes (e.g., aabb)
Duplicative Recessive Epistasis (Complementation)
Other Names: Complementation.
Definition: This occurs when a homozygous recessive genotype for either of two interacting genes masks the expression of the dominant allele of the other gene. In other words, two dominant alleles (one from each gene) are necessary to produce a specific phenotype.
Example: Sweet Pea Flower Color
Parental Cross (P1): White (AAbb) $ imes$ White (aaBB).
Initially, both parents appear white, which might seem counterintuitive if one expects color from dominant alleles. The key is that the homozygous recessive state for either gene masks the ability to produce color.
F1 Generation (AaBb): All purple.
This seems magical – crossing two white flowers yields a new color (purple).
F1 Intercross (AaBb imes AaBb): Expected 9:3:3:1 genotypic ratio. The observed phenotypic ratio is 9:7.
Phenotypes and Genotypes:
Purple Flowers (9/16): Must have at least one dominant allele for both genes (e.g., AB). This genotype allows both biochemical steps to proceed to produce purple pigment.
White Flowers (7/16): Any genotype that is homozygous recessive for at least one of the genes will result in a white phenotype. This includes:
A_bb (3/16)
aaB_ (3/16)
aabb (1/16)
Biochemical Mechanism:
A colorless precursor is converted by Enzyme A (controlled by dominant A) to a colorless intermediate.
The colorless intermediate is converted by Enzyme B (controlled by dominant B) to purple pigment.
If either Enzyme A (due to aa) or Enzyme B (due to bb) is non-functional, the pathway is blocked, and the flowers remain white.
Ratio: 9 (Purple) : 7 (White).
Complementation Test
Purpose: Used to determine if two mutations (that produce the same phenotype) are located in the same gene (allelic) or in different genes.
How it works: Individuals with the two different mutations are crossed.
Complementation Occurs: If the offspring display a wild-type (normal) phenotype, it means the mutations are in different genes. Each parent supplied a functional copy of the gene that the other parent's mutation inactivated. (This is what happened in the sweet pea example: two white parents, each homozygous recessive for a different gene, produced purple offspring because they complemented each other).
No Complementation: If the offspring still display the mutant phenotype, it means the mutations are in the same gene (allelic). Neither parent could supply a functional copy to compensate for the other's mutation in that specific gene.
Example: Hearing Impairment
Two individuals with impaired hearing mate. If their children have normal hearing, it indicates complementation. The parents likely had mutations in different genes important for hearing, and each contributed a functional copy of the gene the other lacked, leading to the normal phenotype in their offspring.
Other Modifications to Gene Expression and Inheritance
Sex-Influenced Traits
Definition: Traits controlled by autosomal genes (not on sex chromosomes), but their expression is influenced by sex hormones.
Example: Male Pattern Baldness
Genotypes:
BB (homozygous dominant): Full head of hair in both males and females.
bb (homozygous recessive): Hair loss in both males and females (but more pronounced in males).
Bb (heterozygous): Shows hair loss in males (due to testosterone) but no effect (or only thinning) in females (less influenced by hormones).
Sex-Limited Traits
Definition: Traits controlled by autosomal genes, but expressed only in one sex, typically due to sex hormones.
Penetrance: Often 0\% in the other sex.
Examples:
Beard growth (limited to males).
Breast development and milk production (limited to females).
Cytoplasmic Inheritance
Definition: Inheritance of genetic material located in the cytoplasm, specifically in organelles like mitochondria and chloroplasts (in eukaryotes).
Mechanism: During oogenesis, the ovum (egg cell) receives the vast majority of cytoplasm and organelles. Sperm, in contrast, sheds most of its cytoplasm and organelles during fertilization, primarily contributing only its nucleus (DNA).
Maternal Inheritance: Consequently, mitochondrial and chloroplast DNA is almost always passed exclusively from the maternal parent to all offspring.
Pedigree Characteristics:
Affected mothers pass the trait to all of their children (both sons and daughters).
Affected fathers do not pass the trait to any of their children.
Example: A genetic issue in a mother's mitochondrial DNA will affect all her children. Her sons, even if affected, will not pass it on to their children if they marry an unaffected woman.
Example: Leber's hereditary optic neuropathy (LHON) causing blindness.
Genomic Imprinting
Definition: A phenomenon where genes from the mother and father are regulated differently. One copy of a gene (either maternal or paternal) is expressed, while the other is silenced (turned off) through epigenetic mechanisms.
Mechanism: Imprinting involves specific gene inactivation, often by methylation or compacting into heterochromatin, to control biological outcomes like offspring size.
Example: Insulin-like Growth Factor 2 (IGF2) and its Receptor
Normal Inheritance:
From Mom: IGF2 receptor gene is activated (on), IGF2 growth factor gene is off.
From Dad: IGF2 receptor gene is off, IGF2 growth factor gene is activated (on).
This specific combination leads to normal offspring weight.
Alterations and Effects:
Deleting the mother's IGF2 receptor (which is normally on) leads to a very large offspring (unregulated growth).
Deleting the father's IGF2 gene (which is normally on) leads to a small offspring (reduced growth).
Deleting both the mother's IGF2 receptor and the father's IGF2 gene can sometimes revert to a normal weight, demonstrating complex interactions.
Significance: Imprinting is crucial for proper development, and its alteration can have devastating effects. Only a few dozen imprinted genes are known, highlighting the specific and precise nature of this regulation.
Conditional Alleles
Definition: Alleles whose expression is dependent on specific environmental conditions, most commonly temperature, during development.
Example: Animal Coat Color (e.g., Siamese cats)
Gene expression for pigment production is temperature-sensitive.
Colder body parts (extremities like paws, ears, tail, nose) lead to darker fur pigmentation.
Warmer body parts (torso) lead to lighter fur pigmentation.
General Relevance: While visual examples are common, conditional alleles can affect non-visual traits (e.g., enzymes important for metabolism, oxygen utilization).
Phenocopy
Definition: An environmentally induced phenotype that resembles a phenotype caused by a genetic mutation, but has no genetic basis.
Example: Birth defects caused by drug exposure during pregnancy that mimic genetic developmental disorders.
The Complexity of Traits
From Simple to Complex: Genetic inheritance moves from simple monogenic models (one gene affecting one trait) to complex interactions involving multiple genes and environmental factors.
Monogene Inheritance: Incomplete dominance, codominance, multiple alleles (often at one chromosomal location).
Gene Interactions: Epistasis, complementation (genes interacting across loci).
Modifying Factors: Penetrance, expressivity, hormones, cytoplasmic factors, imprinting, environmental conditions.
Discontinuous vs. Continuous Traits
Discontinuous Traits:
Definition: Phenotypes fall into distinct, clear-cut categories (either/or).
Examples: Widow's peak (present or absent), tongue rolling (can or cannot), thumb clasping (left over right or right over left).
Continuous Traits:
Definition: Phenotypes vary across a spectrum, with many intermediate forms, and are typically measurable.
Examples: Height, skin pigmentation, weight, hair color.
Polygenic Inheritance: Continuous traits are often controlled by multiple genes. As the number of genes contributing to a trait increases, the number of possible phenotypic classes increases, and the distribution usually forms a bell curve, with most individuals falling in the middle of the spectrum and fewer at the extremes.
Pleiotropy
Definition: A single gene influencing multiple, distinct characteristics or phenotypes.
Mechanism: A single malfunctioning gene can have widespread effects on different organ systems or body functions.
Examples:
Cystic Fibrosis: A single mutation (e.g., in the CFTR gene) can affect multiple organ systems (respiratory, digestive, reproductive) because it affects mucosa production throughout the body.
Phenylketonuria (PKU): A single gene mutation affecting an enzyme involved in metabolism can lead to intellectual disabilities, changes in skin, eye, and hair color.
Multifactorial Traits
Definition: Traits controlled by many genes (polygenic) and are significantly influenced by environmental factors.
Complexity: These are extremely difficult to fully understand or predict due to the intricate interplay between genetics and environment.
Example: Hair color (influenced by multiple genes, diet, sun exposure, chemical treatments like dyeing).
Overall Complexity
Genetic traits are a complex "web" of interactions, where genes influence each other, and their expression is further modified by internal (hormonal, imprinting) and external (temperature, environment) factors. It's crucial to understand these layers of complexity to move beyond simple inheritance models.