Structural Chromosomal Aberrations

Structural Chromosomal Aberrations

• Structural chromosomal aberrations are changes in the normal structure of chromosomes or the arrangement of genetic material within or between individual chromosomes.
• They arise from chromosome breakage and reunion in an abnormal way.
• Chromosome breakage can be caused by X-rays, various chemicals, or can occur spontaneously.

Types of Structural Chromosomal Aberrations

• Balanced structural aberrations: These do not change the amount of genetic material and usually result in a normal phenotype. Examples include translocations and inversions.
• Unbalanced structural aberrations: These involve changes in the amount of genetic material and usually result in an abnormal phenotype. Examples include deletions, duplications, insertions, and rings/isochromosomes.

Deletions

• Definition: A deletion occurs when a part of a chromosome is missing or deleted during DNA replication. Any number of nucleotides can be deleted, from a single base to an entire chromosome segment.
• Characteristics: Deletions are permanent; the lost DNA is degraded and cannot be recovered.
• Types:
  • Terminal deletion: A deletion that occurs at the end of a chromosome.
  • Interstitial deletion (Intercalary): A deletion that occurs within the interior of a chromosome.
  • Microdeletion: Deletions that are too small to be detected by karyotyping. They are often associated with physical abnormalities in children.

Causes of Structural Aberrations

• Unequal crossing over: This occurs during meiosis when homologous sequences are not precisely aligned, leading to unequal exchange of genetic material.
• Mutagens: Exposure to heat, radiation, viruses, or chemicals can cause chromosome breakage that isn't repaired properly.
• Loss from translocation: Chromosomal material may be lost as a result of a translocation.

Effect of Deletion

• The effect of a deletion depends on the location and size of the deleted part.
• Deletion of an entire autosome from the genome is not compatible with life.
• Deletion of the centromere leads to an acentric chromosome, which is lost.
• Large deletions are usually fatal.
• Medium-sized deletions can lead to recognizable human disorders, such as Williams syndrome, infertility, muscular dystrophy, or cystic fibrosis.
• Microdeletions often cause various conditions, including Angelman Syndrome, Prader-Willi Syndrome, and DiGeorge Syndrome.

Cri-du-Chat Syndrome

• Cri-du-chat syndrome is a deletion of part of the short arm of chromosome 5.
• Affected individuals have intellectual disability, a characteristic cry that sounds like a cat, physical abnormalities (low birth weight, small head, wide-set eyes, small jaw, low-set ears, etc.)

Duplications

• Definition: Duplications are the result of doubling of chromosomal segments or entire chromosomes.
• Cause: Unequal crossing over (recombination) during meiosis.
• Types:
  • Tandem duplication: Duplicated segments are adjacent to each other (e.g., ABC ABC).
  • Reverse tandem duplication: Duplicated segments are in the opposite order (e.g., ABC CBA).
  • Terminal duplication: Duplications at the end of a chromosome (tandem or reverse tandem).

Ring Chromosomes

• Definition: Ring chromosomes form when a chromosome undergoes two breaks and the broken ends fuse to form a ring.
• Causes: Often caused by mutagens (like radiation, viruses, chemicals) that cause breaks and these are not rejoined correctly during repair. Can arise spontaneously in development.
• Symptoms: The presence of a ring chromosome can cause abnormalities depending on the size of missing material at the breakpoints within the ring.

Isochromosome

• Definition: An isochromosome is a chromosome with two identical copies of one arm, and the other arm is missing.
• Cause: It is caused by transverse division at the centromere instead of the usual longitudinal division, resulting in one arm being duplicated and the other lost.
• Location: Most commonly found in the X chromosome.

Insertions

• Definition: An insertion occurs when a portion of one chromosome is deleted from its original position and inserted into another chromosome.
• Location: Inserting the segment can occur in any location within a non-homologous chromosome.

Inversions

• Definition: An inversion is a structural chromosomal aberration where a segment of a chromosome is excised and reintegrated in an orientation 180 degrees different from its original orientation.
• Types:
  • Paracentric inversion: Inversions that do not include the centromere and do not change the length of chromosome arms.
  • Pericentric inversion: Inversions that include the centromere and do change the length of chromosome arms.

Translocations

• Definition: A translocation is a structural chromosomal aberration where sections of two chromosomes have exchanged places.
• Types:
  • Reciprocal translocation: An exchange of segments between non-homologous chromosomes.
  • Nonreciprocal translocation: A one-way transfer of genetic material from one chromosome to another non-homologous chromosome.
  • Robertsonian translocation: A type of translocation where two acrocentric chromosomes fuse at their centromeres. A resulting chromosome is very large, and the other chromosome fragments are typically lost.

Numerical Chromosomal Aberrations

• Aneuploidy: Numerical chromosomal aberration where there is one or more additional chromosomes or their absence from the chromosomes pair. Examples include Trisomy, Monosomy.
• Euploidy: Numerical chromosomal aberration where the chromosome number is a multiple of the haploid number (e.g., triploidy, tetraploidy). Examples include Monoploidy, Diploidy, Polyploidy.
  • Monoploidy: One set of chromosomes (n).
  • Diploidy: Two sets of chromosomes (2n).
  • Polyploidy: Three or more sets of chromosomes.

Additional Information

• Many of the chromosomal aberrations described lead to embryonic/fetal loss.
• Trisomy of specific chromosomes is sometimes viable and results in specific phenotypes.

Explore the intricacies of structural chromosomal aberrations, including their causes and types. Understand the distinctions between balanced and unbalanced aberrations, and learn about specific examples like deletions and duplications. This quiz will test your knowledge of chromosome structure and genetic material.