Pericentric Inversion

• Chromosome aberrations are structural changes that can lead to genetic disorders, developmental issues, and diseases
• These aberrations disrupt the normal sequence of genetic material, affecting gene expression and inheritance patterns

Inversions

• Inversions involve a chromosome segment breaking off, flipping 180 degrees, and reattaching
• Inversions may not cause symptoms, but can lead to genetic disorders based on affected genes
• Pericentric inversion includes the centromere
• Paracentric inversion does not include the centromere

Pericentric Inversion

• A chromosome breaks on either side of the centromere
• The segment rotates 180 degrees and reattaches in reverse order
• This alters the arrangement of genetic material
• Most individuals with pericentric inversions do not have health problems
• These are often discovered through genetic testing if there is a family history of birth defects, infertility, or miscarriage
• Pericentric inversions can affect fertility by interfering with chromosome alignment during meiosis, potentially leading to miscarriages or difficulty conceiving
• During meiosis, chromosomes form a loop to align correctly, allowing genetic material exchange
• If the inversion aligns correctly during crossover, offspring inherit a balanced set of chromosomes and are generally healthy but carry the inversion (50% chance)
• Incorrect crossover can result in unbalanced chromosomes, causing developmental or health issues, potentially leading to miscarriage, intellectual disabilities, or growth delays
• Genetic counseling is important for those with a family history of inversions, especially when planning a family, as genetic tests can help determine the risk of passing on unbalanced chromosomal material

Duplications

• Duplication occurs when a segment of a chromosome is copied and appears twice on the homologous chromosome
• The extra genetic material can affect gene dosage
• It often occurs due to non-homologous recombination during meiosis, where a deleted chromosomal fragment attaches to its homologous chromosome, resulting in two copies of the same segment
• Small duplications may not have noticeable effects, while larger duplications can lead to more severe genetic conditions
• An extra copy of certain genes can cause gene dosage effects, leading to overexpression or disruption of gene function
• May result in developmental abnormalities or diseases such as cognitive disabilities, heart defects, or growth issues
• A duplication example is Charcot-Marie-Tooth disease, which can be caused by duplication of the PMP22 gene, leading to peripheral nerve damage

Deletions

• Deletion occurs when a chromosome breaks at two points, and the segment between the breaks is lost
• The loss of genetic material can have varying effects depending on the genes involved
• Deletions can happen during meiosis or due to environmental factors like radiation
• The results in a smaller chromosome with fewer genes
• This results in the loss of genes, which can significantly impact an individual’s development, health, and fertility
• Larger deletions may be visible under a microscope, while smaller deletions often require molecular cytogenetic techniques like FISH or array analysis to detect
• Microdeletions are so small that they cannot be seen with a light microscope, and can lead to specific syndromes
• An example Microdeletion: DiGeorge syndrome can be caused by a microdeletion on chromosome 22
• Deletions may result in syndromes associated with loss of specific gene functions
• The condition severity depends on the deletion size and missing genes

Isochromosome

• Isochromosome is a derivative chromosome where both arms are identical after the centromere divides transversely instead of longitudinally
• Results in either two short arms or two long arms on the chromosome
• Isochromosomes are named based on the duplicated arm, such as isochromosome p if the short arm (p) is duplicated
• Isochromosomes can lead to genetic disorders depending on which chromosome is affected
• For example, Turner syndrome often involves isochromosome formation on the X chromosome, which can affect development and fertility in females

Ring Chromosome

• A ring chromosome occurs when both ends of a chromosome break, and the broken ends join together, forming a circular structure
• The ends of the chromosome fuse, causing the loss of material distal to the breaks
• The formation leads to loss of some genetic material near the breakpoints, leading to the loss of essential genes
• Approximately 5% of cases of Turner Syndrome are caused by a ring chromosome
• The loss of genetic material can cause developmental and health problems depending on the size and location of the loss

Marker Chromosomes

• Macrochromosomes are small chromosomes that may be difficult to detect using traditional chromosome analysis techniques
• They may be too small to be easily characterized under a microscope but can still carry genetic information
• These chromosomes are often detected using advanced techniques like FISH or array analysis
• Marker chromosomes are extra fragments or chromosomal fragments that are not easily classified using traditional methods
• They can form through transverse or longitudinal separation at the centromere, resulting in isochromosomes, or through inverted duplication of chromosome segments
• Some marker chromosomes are pathogenic, causing disorders such as Pallister-Killian syndrome or cat-eye syndrome, while others may not cause noticeable symptoms
• The impact depends on the nature of the genetic material in the macrochromosome

Key Characteristics of Marker Chromosomes

• Size: They are often smaller than normal chromosomes, making them harder to identify using traditional methods
• Unusual Structure: They may have irregular shapes, such as extra copies of chromosome segments (duplications), deletions, or rearrangements

Origin: Marker chromosomes can arise from several mechanisms, including:

• Isochromosomes: Chromosomes that have lost their centromere and replicate one of their arms, leading to two identical arms
• Chromosomal Translocations: Parts of one chromosome might break off and attach to another, creating a fragment
• Duplications or Deletions: Sections of chromosomes may be duplicated or deleted
• Clinical Relevance
• Some marker chromosomes are harmless, causing no noticeable symptoms
• Other marker chromosomes, however, can cause genetic disorders, like Pallister-Killian syndrome or cat-eye syndrome, depending on the genetic material they contain
• Marker chromosomes are typically identified with specialized genetic techniques such as fluorescence in situ hybridization (FISH) because they are too small or too structurally altered to be seen easily with traditional chromosomal analysis (like a standard karyotype)

Summary

• Chromosomal Aberrations: Structural changes like inversions, duplications, deletions, isochromosomes, ring chromosomes, and macrochromosomes can lead to genetic disorders, developmental issues, and diseases, depending on the size, location, and nature of the chromosomal change
• Inversions and duplications typically have a more subtle impact unless inherited in an unbalanced manner, leading to significant developmental and health challenges
• Deletions can cause microdeletion syndromes, which require molecular diagnostic tools for detection and may result in specific syndromes depending on the size of the deletion and the genes involved
• Understanding these chromosomal abnormalities is essential for genetic counseling, especially when there is a family history of birth defects, infertility, or miscarriage