Gene Interactions: Dominance, Penetrance, Expressivity, and Epistasis CH 4

Chapter 4: Gene Interactions

Introduction

This chapter explores the molecular and genetic basis of how alleles interact to produce phenotypes, including variations on Mendelian inheritance, penetrance, expressivity, and gene interactions such as epistasis. Understanding these concepts is essential for interpreting genetic outcomes and predicting inheritance patterns.

Transmission Genetics Review

Probability and Pedigrees

• Probability in Genetics: Used to predict outcomes of gamete production (meiosis) and phenotypes/genotypes from crosses involving multiple traits.

• Fork-lined Method: A systematic approach to calculate probabilities in genetic crosses.

• Pedigree Analysis: Utilized to predict inheritance patterns within families.

Haplosufficient vs. Haploinsufficient Alleles

Definitions and Implications

• Haplosufficient: An allele is haplosufficient if a single copy (n=1, haploid) is sufficient to produce the wild type phenotype. The wild-type allele is dominant.

• Haploinsufficient: An allele is haploinsufficient if a single copy is not sufficient to produce the wild type phenotype. The wild-type allele is recessive.

• Example: In genotype Hh, if H is dominant and produces the wild phenotype, H is haplosufficient. If h is recessive and does not produce the wild phenotype with one copy, h is haploinsufficient.

Effects of Mutation

Loss of Function Mutations

• Loss of Function: Mutant alleles often result in a loss of function, meaning the gene product is reduced or absent.

• Phenotypic Consequence: If the wild-type allele is haplosufficient, the phenotype remains wild-type in heterozygotes. If haploinsufficient, the mutant phenotype appears even with one wild-type allele.

• Diagram: Homozygous wild-type produces normal product; homozygous mutant produces none; heterozygote may produce reduced product.

Variations on Mendelian Dominance

Complete, Incomplete, and Codominance

• Complete Dominance: One allele is fully dominant over the other, following Mendel's laws.

• Incomplete (Partial) Dominance: Heterozygotes display a phenotype intermediate between the two homozygotes, due to partial contribution from both alleles. This results in a blend of traits.

• Codominance: Both alleles in a heterozygote are fully expressed, resulting in a phenotype that shows both traits distinctly (not blended).

• Example: ABO blood group system in humans demonstrates codominance.

Mendel's Complete Dominance vs. Incomplete Dominance

Phenotypic Manifestations

• Complete Dominance: Follows Mendel's 2nd postulate; one allele is dominant, the other recessive.

• Incomplete Dominance: Blending of phenotypes occurs in heterozygotes, which is an exception to Mendel's 2nd postulate.

• Example: Flower color in snapdragons: Red (R1R1), White (R2R2), Pink (R1R2).

Intermediate Phenotypes in Incomplete Dominance

Genotypic and Phenotypic Ratios

• Heterozygotes: Show intermediate (blended) phenotypes due to partial dominance.

• Example: In snapdragons, R1R2 genotype produces pink flowers, intermediate between red and white.

• F2 Generation Ratio: 1 red : 2 pink : 1 white

$ext{F}_2 ext{ ratio: } 1 ext{ R}^1 ext{R}^1 : 2 ext{ R}^1 ext{R}^2 : 1 ext{ R}^2 ext{R}^2$

Codominance and ABO Blood Groups

Genetic Basis and Phenotypes

• Codominance: Both alleles are expressed in the heterozygote, as seen in the ABO blood group system.

• Genotypes and Phenotypes:

Genotype	Phenotype
IAIA, IAi	A
IBIB, IBi	B
IAIB	AB
ii	O

• Antigens: A and B antigens are present on red blood cells, determined by the IA and IB alleles. The i allele produces no antigen.

• Inheritance: IA and IB are codominant to each other and dominant over i.

Predicting Offspring Phenotypes: A x B Cross

Punnett Square Analysis

• Potential Offspring Phenotypes: When parents are heterozygous for A (IAi) and B (IBi), offspring can be A, B, AB, or O.

Parent Genotypes	A	B	AB	O
IAi x IBi	1/4	1/4	1/4	1/4

Penetrance and Expressivity

Definitions and Examples

• Penetrance: The proportion of individuals with a specific genotype who display the expected phenotype. 100% penetrance means all individuals show the phenotype.

• Incomplete Penetrance: Not all individuals with the genotype express the phenotype.

• Expressivity: The degree or intensity of the phenotype expressed by individuals with the same genotype.

• Variable Expressivity: Individuals with the same genotype show a range of phenotypic intensities.

• Example: Polydactyly (extra fingers) shows incomplete penetrance and variable expressivity.

Gene Interactions: Epistasis

Definition and Types

• Gene Interaction: Multiple gene products contribute to a common phenotype.

• Epistasis: Occurs when one gene pair masks or modifies the effect of another gene pair. Can be antagonistic or complementary.

• Recessive Epistasis: Homozygous recessive alleles at one locus (gene 1) override the expression of another gene (gene 2).

• Example: Bombay phenotype: FUT1 (hh) is recessive epistatic to ABO blood group gene, resulting in phenotype O regardless of ABO genotype.

Genotype (FUT1, ABO)	Phenotype
hh, any ABO	O (Bombay)
H_, IAIA or IAi	A
H_, IBIB or IBi	B
H_, IAIB	AB
H_, ii	O

• Hint: A phenotypic ratio expressed in 16 parts (e.g., 9:3:3:1 or 3:6:3:4) suggests epistasis is occurring.

Summary Table: Key Terms and Concepts

Term	Definition	Example
Haplosufficient	One allele sufficient for wild type phenotype	H in Hh
Haploinsufficient	One allele not sufficient for wild type phenotype	h in Hh
Complete Dominance	One allele fully dominant	Red flower (A)
Incomplete Dominance	Blended phenotype in heterozygote	Pink flower (R1R2)
Codominance	Both alleles fully expressed	AB blood type
Penetrance	Proportion showing phenotype	Polydactyly
Expressivity	Intensity of phenotype	Dog coat color
Epistasis	One gene masks another	Bombay phenotype

Additional info: These notes expand on the provided slides by including definitions, examples, and tables for clarity and completeness, suitable for exam preparation in a college genetics course.