Extensions of Mendelian Genetics: Comprehensive Study Notes

Extensions of Mendelian Genetics

Introduction

This chapter explores how classical Mendelian inheritance is extended by various genetic phenomena, including multiple alleles, incomplete dominance, codominance, gene interactions, and the influence of lethal alleles. These concepts are fundamental for understanding the complexity of genetic inheritance beyond simple dominant and recessive relationships.

4.1 Alleles Alter Phenotypes in Different Ways

Alleles and Mutation

• Alleles: Alternative forms of a gene that arise by mutation and are found at the same place on a chromosome.

• Mutation: The ultimate source of alleles, leading to new phenotypes by altering the functional activity of gene products.

• Mutations can affect phenotypes by:

  • Eliminating enzyme function

  • Changing relative enzyme efficiency

  • Altering overall enzyme function

• Wild-type (wt) allele: The allele that occurs most frequently in nature and is usually, but not always, dominant.

Types of Mutations

• Loss-of-function mutations: Result in reduced or eliminated activity of the gene product, often causing a new phenotype due to the loss of wild-type function.

• Gain-of-function mutations: Enhance the function of the wild-type gene product, often increasing the quantity or activity of the gene product.

• Neutral mutations: Do not affect phenotype or evolutionary fitness.

4.2 Geneticists Use a Variety of Symbols for Alleles

Allele Notation

• Dominant alleles: Indicated by italic uppercase letters (e.g., D) or letter combinations (e.g., Wr).

• Recessive alleles: Indicated by italic lowercase letters (e.g., d) or groups of letters (e.g., wr).

• Mutant alleles: Indicated by italic letters (e.g., e).

• Wild-type alleles: Indicated by an italic letter plus a superscript + (e.g., e+).

Example: Drosophila melanogaster Body Color

• Ebony mutant phenotype: e

• Normal gray (wild-type): e+

Genotype	Phenotype
e+/e+	Gray homozygote (wild type)
e+/e	Gray heterozygote (wild type)
e/e	Ebony homozygote (mutant)

If no dominance exists, italic uppercase letters and superscripts are used (e.g., R1, R2, CW, CR).

4.3 Neither Allele is Dominant in Incomplete, or Partial, Dominance

Incomplete Dominance

• Neither allele is dominant; the heterozygote displays an intermediate phenotype.

• Example: Snapdragons

  • Red snapdragon × white snapdragon → F1: pink flowers

  • F2 generation: 1/4 red, 1/2 pink, 1/4 white

  • Phenotypic and genotypic ratios are the same; each genotype has its own phenotype.

Human Example: Tay-Sachs Disease

• Homozygous recessives lack hexosaminidase A activity, leading to a fatal lipid-storage disorder.

• Heterozygotes have about half the normal enzyme activity, showing incomplete dominance at the biochemical level.

4.4 In Codominance, the Influence of Both Alleles in a Heterozygote is Clearly Evident

Codominance

• Both alleles in a heterozygote are fully expressed; there is no dominance or blending.

• Example: MN Blood Group in Humans

Genotype	Phenotype
LMLM	M
LMLN	MN
LNLN	N

Crossing two heterozygotes yields a 1:2:1 ratio of phenotypes.

4.5 Multiple Alleles of a Gene May Exist in a Population

Multiple Alleles

• More than two alleles exist for a gene within a population, though any individual can only carry two alleles.

• Each allele may confer a unique phenotype or mode of inheritance.

Example: Human ABO Blood Groups

• Three alleles: IA, IB, and i

• IA and IB produce A and B antigens, respectively; i produces no antigen.

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

Genotype	Antigen	Phenotype
IAIA	A	A
IAi	A	A
IBIB	B	B
IBi	B	B
IAIB	A, B	AB
ii	Neither	O

A and B antigens are carbohydrate groups bound to lipids on red blood cells. The H substance is a precursor; O blood types (ii) only have the H substance.

4.6 Lethal Alleles Represent Essential Genes

Essential and Lethal Alleles

• Essential genes: Required for survival; mutations tolerated if heterozygous, but homozygous recessive is lethal.

• Lethal allele: Mutation in an essential gene that can cause organismal death, often inherited recessively.

• Dominant lethal allele: One copy is sufficient to cause death (e.g., Huntington disease).

Example: Agouti Gene in Mice

• Agouti allele (A) and mutant yellow allele (AY).

• AY is dominant for coat color but recessive lethal; AYAY genotype is lethal.

4.7 Combinations of Two Gene Pairs with Two Modes of Inheritance Modify the 9:3:3:1 Ratio

Gene Interactions and Modified Ratios

• When two different modes of inheritance are combined, the classic 9:3:3:1 Mendelian ratio is modified.

• Example: Two heterozygotes, both autosomal recessive for albinism and both blood type AB, produce offspring with a variety of phenotypes due to the interaction of Mendelian and multiple allele inheritance.

Genotype (Pigmentation)	Genotype (Blood Type)	Phenotype
AA or Aa	IAIB	Pigmented, AB
aa	ii	Albino, O
...	...	Other combinations

Additional info: The table above is a simplified representation; the actual cross would yield 16 possible genotype combinations.