Extensions of Mendelian Inheritance: Single-Gene and Multi-Gene Interactions

Extensions to Mendel for Single-Gene Inheritance

Overview

While Mendel's laws provide a foundation for understanding inheritance, many traits exhibit patterns that deviate from simple Mendelian ratios. These deviations arise due to variations in dominance, the presence of multiple alleles, pleiotropy, and gene-environment interactions.

• Dominance is not always complete: Includes incomplete dominance and codominance.

• Genes may have more than two alleles: Multiple alleles can exist in a population, though individuals carry only two.

• Pleiotropy: A single gene may influence multiple, seemingly unrelated traits.

Dominance Relationships

• Complete Dominance: The heterozygote's phenotype is identical to one of the homozygotes.

• Incomplete Dominance: The heterozygote displays an intermediate phenotype between the two homozygotes.

• Codominance: The heterozygote expresses phenotypes of both homozygotes simultaneously.

Example: Antirrhinum majus (snapdragon) flower color demonstrates incomplete dominance. Crossing red (A1A1) and white (A2A2) yields pink (A1A2) F1 progeny. F2 ratio: 1 red : 2 pink : 1 white.

• Molecular Basis: The normal allele produces an enzyme for pigment. Two normal alleles = red, one = pink, none = white.

Example: Codominance in lentil seed coat patterns: crossing spotted (CSCS) and dotted (CDCD) yields F1 with both patterns (CSCD).

Multiple Alleles

Genes can have more than two alleles in a population, though each individual carries only two. Dominance relationships are unique to each allele pair.

• Example: Human ABO blood groups are determined by three alleles (IA, IB, i). IA and IB are codominant; both are dominant to i.

Phenotype (Blood Group)	Genotype
O	ii
A	IAIA or IAi
B	IBIB or IBi
AB	IAIB

Medical Implications: Blood transfusions require matching antigens and antibodies. Type AB is a universal recipient; type O is a universal donor.

Blood Type	Antibodies in Serum
A	Antibodies against B
B	Antibodies against A
AB	None
O	Antibodies against A and B

Dominance Series and Multiple Alleles in Other Organisms

• Lentil Seed Coats: Five alleles (marbled-1, marbled-2, spotted, dotted, clear) form a dominance series: marbled-1 > marbled-2 > spotted = dotted > clear.

• Human Histocompatibility Antigens (HLA): Each gene (HLA-A, HLA-B, HLA-C) has hundreds to over a thousand codominant alleles, resulting in extreme phenotypic diversity.

Mutation and Allele Frequency

• Mutation: Spontaneous changes in genetic material create new alleles. Mutation rates in gametes are typically $10^{-4}$ to $10^{-6}$ per generation.

• Allele Frequency: The proportion of a specific allele among all gene copies in a population. The most common allele is 'wild-type' (+); rare alleles are 'mutant'.

• Monomorphic gene: Only one common wild-type allele.

• Polymorphic gene: More than one common allele; high-frequency alleles are called 'common variants'.

Pleiotropy

Pleiotropy occurs when a single gene affects multiple traits. For example, mutations in a gene required for cilia and flagella function can cause both respiratory issues and sterility in humans.

• Heterozygotes may show a visible phenotype.

• Homozygotes may be lethal (e.g., AY allele in mice).

Recessive Lethal Alleles

• Example: The AY allele in mice is dominant for yellow coat color but recessive lethal. Crosses between yellow mice yield a 2:1 ratio of yellow to agouti offspring, as AYAY individuals are not viable.

Pleiotropy in Sickle-Cell Anemia

Sickle-cell anemia is caused by a mutation in the β-globin gene (HbS). The disease is pleiotropic, affecting red blood cell shape, anemia, heart failure, and malaria resistance. Dominance relationships vary by trait:

• Normal allele (HbA) and mutant allele (HbS).

• HbS is recessive for anemia, but heterozygotes (HbAHbS) are resistant to malaria (overdominance).

Phenotype	Genotype	Dominance
Normal RBCs	HbAHbA	Dominant
Sickle-cell disease	HbSHbS	Recessive
Carrier (sickle trait)	HbAHbS	Codominant/Overdominant (malaria resistance)

Summary Table: Alterations of the 3:1 Monohybrid Ratio

Extension	Effect on Heterozygote	F2 Ratio
Incomplete dominance	Intermediate phenotype	1:2:1
Codominance	Both parental traits expressed	1:2:1
Recessive lethal	Heterozygotes viable, homozygous lethal	2:1
Pleiotropy	Multiple traits affected	Varies

Additional info:

• These notes cover the first part of Chapter 2, focusing on single-gene inheritance and its extensions. Further sections (not included in the images) would address two-gene interactions, complex traits, and comprehensive examples such as dog coat color genetics.