Chromosomal Aberrations: Variation at the Chromosome Level (Chapter 10 Study Notes)

Chromosomal Aberrations

Introduction

Chromosomal aberrations refer to structural and numerical changes in chromosomes that can affect genetic information and organismal traits. These variations occur at the chromosome level and are a major source of genetic diversity and disease. This topic covers the types, mechanisms, and consequences of chromosomal aberrations, including ploidy changes, chromosome breaks, rearrangements, and transposition.

Ploidy

Genome Composition

Ploidy describes the number of complete sets of chromosomes in a cell. It is a fundamental concept in genetics, affecting inheritance and cell function.

• Haploid (n): One set of chromosomes (e.g., gametes).

• Diploid (2n): Two sets of chromosomes (e.g., somatic cells in humans).

• Triploid (3n), Tetraploid (4n), etc.: More than two sets; collectively called polyploid.

• Euploid: Cells with an exact multiple of the haploid number (n, 2n, 3n, etc.).

• Aneuploid: Cells with chromosome numbers that are not exact multiples of the haploid set (e.g., 2n+1, 2n-1).

Example: Human somatic cells are diploid (2n = 46), while gametes are haploid (n = 23).

Species	Diploid Chromosome Number (2n)
Carp	104
Cat	38
Chicken	78
Chimpanzee	48
Cow	60
Dog	78
Frog	26
Fruit fly	8
Human	46
Mouse	40
Rat	42
Rhesus monkey	42

Aneuploidy

Mechanisms: Nondisjunction

Aneuploidy arises when chromosomes fail to separate properly during cell division, leading to abnormal chromosome numbers.

• Nondisjunction: Failure of homologous chromosomes (Meiosis I) or sister chromatids (Meiosis II) to separate.

• Trisomy (2n+1): Presence of an extra chromosome.

• Monosomy (2n-1): Loss of a chromosome.

Equation:

$2n + 1$ = Trisomy $2n - 1$ = Monosomy

Gene Dosage: Monosomy vs Trisomy

Consequences and Examples

Gene dosage refers to the number of copies of a gene present in a cell. Changes in dosage can have significant effects on phenotype and viability.

• Monosomy: Usually lethal due to insufficient gene product.

• Trisomy: Can result in developmental disorders (e.g., Down syndrome).

Aneuploidy	Syndrome	Frequency at Birth	Characteristics
Trisomy 13	Patau syndrome	1 in 15,000	Severe intellectual disability, heart defects
Trisomy 18	Edwards syndrome	1 in 8,000	Developmental delay, organ malformations
Trisomy 21	Down syndrome	1 in 700	Characteristic facial features, intellectual disability
47, XXY	Klinefelter syndrome	1 in 1,000	Male with extra X chromosome, infertility
45, XO	Turner syndrome	1 in 2,500	Female with single X chromosome, short stature

Trisomy and Meiosis

Effects on Fertility

Trisomic individuals often experience reduced fertility due to abnormal chromosome pairing and segregation during meiosis.

• Semisterility: Fewer normal gametes are produced.

• Formation of trivalent and univalent structures during meiosis leads to abnormal segregation.

Mosaicism

Definition and Examples

Mosaicism occurs when an individual has two or more genetically distinct cell lines due to mitotic nondisjunction or other events.

• Mitotic nondisjunction: Leads to cells with different chromosome numbers.

• Gynandromorphy: Example in Drosophila where individuals have both male and female tissues.

Polyploidy

Types and Origins

Polyploidy refers to cells or organisms with more than two complete sets of chromosomes. It is common in plants and can arise through several mechanisms.

• Autopolyploid: Chromosomes derived from the same species.

• Allopolyploid: Chromosomes originate from two or more different species.

Example: Wheat is an allopolyploid species.

Mechanisms of Polyploidy Formation

• Multiple fertilizations: Fusion of more than two gametes.

• Nondisjunction: Failure of chromosome separation during meiosis or mitosis.

Benefits of Polyploidy

• Increased fruit/flower size

• Infertility in odd-numbered polyploids (e.g., 3n, 5n) leads to seedless fruits

• Increased heterozygosity

Polyploidy vs Meiosis

Chromosome Pairing and Fertility

• Diploid: Only bivalents form; fertile.

• Autopolyploid (Triploid): Bivalents, monovalents, and trivalents form; usually infertile.

• Allopolyploid: Fertility depends on chromosome pairing; only bivalents lead to fertility.

Chromosome Structure

Types of Chromosomes

Chromosomes are classified based on centromere position:

• Metacentric: Centromere in the middle

• Submetacentric: Centromere slightly off-center

• Acrocentric: Centromere near one end

• Telocentric: Centromere at the end

Chromosome Variation

Causes and Types

Chromosome variation results from DNA double strand breaks (DSB) and subsequent repair or misrepair.

• Terminal deletions

• Interstitial deletions (including those from unequal cross-overs)

• Rearrangements: inversions (paracentric and pericentric), translocations

Deletions: Chromosome Breakage

Types of Deletions

• Terminal deletion: Loss of chromosome end (telomere).

• Interstitial deletion: Loss of an internal segment due to two breaks.

Example: Cri-du-chat syndrome is caused by a terminal deletion on chromosome 5.

Unequal Crossover

Unequal crossing over during meiosis can result in deletions and duplications of genetic material.

• Partial deletion heterozygote: One chromosome has a deletion, the other is normal.

• Partial duplication heterozygote: One chromosome has a duplication, the other is normal.

Detection of Deletions/Insertions

Methods

• Fluorescent In Situ Hybridization (FISH): Uses fluorescent probes to detect specific DNA sequences.

• Unpaired loop formation: During meiosis, unpaired loops indicate deletions, duplications, or insertions.

Pseudodominance

Genetic Mapping

Pseudodominance occurs when a deletion uncovers a recessive allele, revealing its phenotype. This phenomenon can be used to map gene locations.

Chromosome Rearrangements

Inversions

• Paracentric inversion: Inversion does not include the centromere; two breaks in the same arm.

• Pericentric inversion: Inversion includes the centromere; breaks on either side of the centromere.

• Direct consequences: Loss of function if break disrupts gene or gene expression; silent mutation if not.

Summary Table: Types of Chromosomal Aberrations

Type	Description	Example
Aneuploidy	Abnormal number of chromosomes	Down syndrome (Trisomy 21)
Polyploidy	More than two sets of chromosomes	Wheat (hexaploid)
Deletion	Loss of chromosome segment	Cri-du-chat syndrome
Duplication	Extra copy of chromosome segment	Charcot-Marie-Tooth disease
Inversion	Reversal of chromosome segment	Pericentric inversion of chromosome 9
Translocation	Segment moved to another chromosome	Philadelphia chromosome in leukemia

Additional info: These notes expand on the original slides by providing definitions, examples, and context for each type of chromosomal aberration, as well as the mechanisms and consequences involved.