Chromosomal Genetics: The Chromosomal Basis of Inheritance and Sex-Linked Traits

Topic 11: Chromosomal Genetics

Overview

This topic covers the chromosomal basis of inheritance, including Mendelian genetics, the laws of segregation and independent assortment, sex determination mechanisms, and the inheritance of sex-linked and X-linked traits. It also explores the concept of lethal alleles and X-inactivation in female mammals.

14.4 Lethal Alleles

Definition and Types

• Lethal alleles are gene variants that cause death when present in certain genotypes.

• Dominant lethal alleles are rare because they cause death in both homozygotes and heterozygotes, often before the allele can be passed on. Example: Huntington disease (delayed onset allows transmission).

• Recessive lethal alleles cause death only in homozygous individuals. Example: Phenylketonuria (PKU), where individuals lack an enzyme to break down phenylalanine.

• Lethality can occur in utero (miscarriage) or later in life.

• PKU can be managed with supplemental enzymes and dietary restrictions.

15.1 The Chromosomal Basis of Inheritance

Historical Context

• 1860: Mendel proposed "hereditary factors" passed from parent to offspring.

• 1870–1890: Cytologists used microscopy to observe mitosis and meiosis.

• ~1902: Scientists linked chromosome behavior during meiosis to Mendel's laws.

Chromosome Theory of Inheritance

• Genes have specific locations (loci) on chromosomes.

• The Law of Segregation and Law of Independent Assortment are explained by chromosome movement during meiosis.

• DNA was not yet known to be the genetic material at this time.

Law of Segregation

• Alleles for a gene segregate during gamete formation (anaphase I of meiosis).

• Each gamete receives one allele for each gene.

• Fertilization restores the diploid state, recombining alleles at random.

Law of Independent Assortment

• Alleles of genes on different chromosomes assort independently during gamete formation (metaphase I of meiosis).

• Results in genetic variation and a 9:3:3:1 phenotypic ratio in dihybrid crosses.

15.1 Morgan's Flies Support Chromosomal Inheritance

Thomas Hunt Morgan's Experiments

• Used Drosophila melanogaster (fruit fly) as a model organism.

• Short life cycle, many offspring, simple karyotype (3 pairs of autosomes, 1 pair of sex chromosomes).

• Wildtype: most common phenotype in nature; mutant: variation from wildtype.

Key Findings

• Crossed white-eyed males (mutant) with red-eyed females (wildtype): all F1 offspring had red eyes (red is dominant).

• F1 cross produced a 3:1 ratio in F2, but only males had white eyes, indicating the gene is on the X chromosome (sex-linked trait).

15.2 Sex-Linked Genes Exhibit Unique Patterns of Inheritance

Sex Determination Systems

• Sex: Biological classification based on anatomy, physiology, and chromosomes.

• Gender: Cultural/spiritual identity (male, female, non-binary, etc.).

System	Example Organisms	Sex Chromosomes
X-Y	Mammals	XX = female, XY = male
X-O	Grasshoppers, some insects	XX = female, XO = male
Z-W	Birds, some fishes/insects	ZW = female, ZZ = male
Haplo-diploid	Bees, ants	Diploid = female, Haploid = male

Sex-Linked Traits

• Y chromosome: Few genes, mostly related to male development.

• X chromosome: ~1100 genes, many with no Y counterpart.

• Males are hemizygous for X-linked genes (only one copy).

Inheritance Patterns of X-Linked Traits

• Females inherit two X chromosomes (one from each parent); males inherit one X (from mother) and one Y (from father).

• Examples of X-linked traits: Red/green color blindness, Duchenne muscular dystrophy, hemophilia.

F1 Generation

• Females: w+w (heterozygotes), inherit X from both parents.

• Males: w (from mother), Y (from father).

F2 Generation

• Possible genotypes: 25% female homozygous dominant, 25% female heterozygous (carrier), 25% male hemizygous dominant, 25% male hemizygous recessive.

Examples of X-Linked Genes

• Male-patterned baldness

• Red/green color blindness (1 in 12 European men, 1 in 200 European women)

• Wildtype allele: X+; mutant allele: Xc

Inheritance of X-Linked Traits

Parental Genotype	Offspring Outcome
Colour-blind father × wildtype mother	All daughters are carriers, all sons are normal
Carrier mother × normal father	50% daughters carriers, 50% sons affected
Carrier mother × colour-blind father	50% of all children affected, regardless of sex

• Same process applies to other X-linked traits (e.g., Duchenne muscular dystrophy, hemophilia).

15.2 X-Inactivation in Female Mammals

Barr Bodies and Dosage Compensation

• Females have two X chromosomes, but only one is active in each cell; the other is inactivated as a Barr body (discovered by Murray Barr).

• Inactivation occurs early in development and is random (either maternal or paternal X).

• Results in genetic mosaics—heterozygous females have patches of cells expressing different alleles.

Example: Tortoiseshell Cats

• Coat color gene is X-linked; two alleles (black fur XB, orange fur Xb).

• Heterozygous females (XBXb) show patches of black and orange due to X-inactivation.

• Piebald gene (S) controls white spotting; incomplete dominance (SS = solid, Ss = some spotting, ss = white).

Summary Table: Sex Determination Systems

System	Sex Chromosomes	Determination
X-Y	XX (female), XY (male)	Sperm determines sex
X-O	XX (female), XO (male)	Presence/absence of X in sperm
Z-W	ZW (female), ZZ (male)	Egg determines sex
Haplo-diploid	Diploid (female), Haploid (male)	Fertilization status

Key Equations and Concepts

• Law of Segregation:

$\text{Each gamete receives one allele for each gene}$

• Law of Independent Assortment:

$\text{Alleles of different genes assort independently during gamete formation}$

• Phenotypic Ratio for Dihybrid Cross:

$9:3:3:1$

Learning Objectives

• Explain the laws of segregation and independent assortment of genes on separate chromosomes.

• Describe mechanisms of sex determination in animals.

• Explain inheritance patterns of genes on the X chromosome.

• Describe inheritance of linked genes and organelle genes.

• Explain the role of aneuploidy in chromosomal disorders.