Chromosome Mutations: Number and Structure Variations

Posted on Mar 29, 2025 in Biology

Lecture 15: Chapter 8

Chromosome Mutations: Variation in Number and Arrangement

Visualizing Chromosomes

Cytogenetics: The study of chromosomes within cells.

Chromosomes are designated based on the relative placement of their centromere. (See Figure 2.3 for visualization).

Human Karyotypes and idealized banding patterns group chromosomes: A(1-3), B(4-5), C(6-12), D(13-15), E(16-18), F(19-20), G(21-22).

Chromosome Numbers

Key terms include Aneuploidy, Euploidy, and Polyploidy. (Refer to Table 8.1 for examples).

Chromosome numbers vary across organisms. The haploid number (n) is the number of chromosomes in a gamete. The euploid number for a diploid organism is typically twice the haploid number (2n).

Nondisjunction

Meiotic nondisjunction refers to errors in chromosome segregation during meiosis. This leads to aneuploid gametes, which can result in aneuploid zygotes or organisms. Aneuploidy is a condition where the chromosome number is not an exact multiple of the haploid number for that species. (Illustrated in Figure 8.1).

Aneuploidy Conditions

Monosomy: Having 2n-1 chromosomes (where n = haploid chromosome number). In animals, this condition is often lethal due to insufficient gene products or the uncovering of lethal recessive mutations. It is generally better tolerated in plants.

Trisomy: Having 2n+1 chromosomes. This condition is generally better tolerated than monosomy in both plants and animals.

Trisomy Examples

Trisomy in Jimson Weed: Jimson weeds (Datura stramonium) tolerate trisomy very well. Trisomy for different chromosomes leads to distinct phenotypes (physical appearances).

Trisomy 21: Down Syndrome (47, 21+)

  • Occurs in approximately 1/800 live births.
  • Associated with Group G chromosomes.
  • Physical, psychomotor, and mental development are typically retarded.
  • Individuals usually exhibit 6-8 characteristics out of a possible 12-14 associated with the syndrome (showing variation).
  • Increased susceptibility to Alzheimer’s disease, respiratory diseases, heart malformations, and leukemia (rate is ~20x higher).
  • Reduced susceptibility to solid tumors (like lung cancer and melanoma), possibly due to the extra copy of a gene (like DSCR1, sometimes implicated with VEGF pathways) that may inhibit angiogenesis.
  • The incidence of Trisomy 21 increases with maternal age.
  • About 95% of cases result from nondisjunction during ovum formation.

Trisomy 13: Patau Syndrome (47, 13+)

  • Occurs in approximately 1/19,000 live births.
  • Characteristics include severe mental retardation, growth failure, deafness, heart defects, cleft lip and palate, polydactyly, and cryptorchidism.

Trisomy 18: Edwards Syndrome (47, 18+)

  • Occurs in approximately 1/8,000 live births.
  • Characteristics include growth failure, abnormal kidneys, prominent heel, and a short sternum.
Aneuploidy Frequency in Humans

Analysis of miscarried fetuses reveals substantial aneuploidy. All possible autosomal trisomies have been observed, though monosomies are rare. An estimated 25% of human conceptions spontaneously miscarry, and about 50% of these miscarriages involve a chromosomal abnormality. It’s estimated that 10-30% of all fertilized human eggs are aneuploid.

Auto- and Allopolyploidy

(See Figure 8.6 for comparison)

Polyploidy

Polyploidy is the condition of having more than two multiples of the haploid chromosome set (e.g., Triploidy = 3n, Tetraploidy = 4n). Sets with an odd number of chromosomes (e.g., 3n) are often not reliably maintained from generation to generation, leading to sterility.

Polyploidy originates in two main ways:

  1. Autopolyploidy: Results from the addition of one or more extra sets of chromosomes identical to the normal haploid complement of the same species.
  2. Allopolyploidy: Results from the combination of chromosome sets from different species, typically occurring as a consequence of hybridization.

The difference between autopolyploidy and allopolyploidy lies in the genetic origin of the extra chromosome sets, as shown in Figure 8.6.

Polyploidy Induction

(See Figure 8.7)

Colchicine is a chemical agent often used experimentally to induce polyploidy by interfering with spindle fiber formation, effectively doubling the chromosome number.

Generally, polyploids with an even number of chromosome sets (e.g., 4n tetraploids) tend to be fertile, while those with odd sets (e.g., 3n triploids) are often sterile due to problems with chromosome pairing and segregation during meiosis.

Autopolyploids

Autopolyploids tend to be larger than their diploid counterparts due to larger cell sizes. This may relate to alterations in cell cycle regulation (e.g., G1 phase duration allowing more growth). They can be valuable in agriculture and horticulture (e.g., larger fruits, flowers). However, they often need to be propagated asexually, especially if sterile.

Endopolyploidy

Endopolyploidy is a condition where only certain cells or tissues within an otherwise diploid organism become polyploid (e.g., some liver cells in humans).

Chromosomal Rearrangements

Variations can also occur in the structure or arrangement of chromosomes. Major types include:

  • Deletion: Loss of a chromosome segment.
    • Origin of terminal deletion: Loss from the end of a chromosome.
    • Origin of intercalary deletion: Loss from within the chromosome arm.
    • Formation of deletion loop: Occurs during meiosis in heterozygotes.
    • Segmental deletion: A specific type of deletion.
  • Duplication: Repetition of a chromosome segment.
    • Duplication and redundancy: Provides extra gene copies.
    • Duplication as a substrate for evolution: Allows one copy to mutate while the other maintains original function.
    • Copy number variation (CNV) in humans: Common variations involving duplications and deletions.
  • Inversion: A segment of a chromosome is reversed end-to-end.
    • Origin of inversion: Requires two breaks in the chromosome.
    • Inversion heterozygote: An individual with one normal and one inverted chromosome.
    • Inversion and crossovers: Crossovers within the inverted region in heterozygotes can lead to nonviable gametes.
    • Influence of inversions: Can suppress recombination and have evolutionary significance.
  • Translocation: Movement of a segment from one chromosome to a non-homologous chromosome.
    • Nonreciprocal translocation: One-way transfer.
    • Reciprocal translocation: Exchange of segments between two non-homologous chromosomes.
    • Robertsonian translocations: Fusion of two acrocentric chromosomes near the centromere, often with loss of the short arms. A common cause of Familial Down syndrome (Trisomy 21).
  • Fragile Sites: Specific locations on chromosomes susceptible to breakage.
    • Fragile X syndrome (Martin-Bell syndrome): Caused by expansion of a trinucleotide repeat on the X chromosome, leading to intellectual disability.
    • Fragile sites and cancer: Some fragile sites are associated with genes involved in cancer development.