Genetics 9 - Chromosome Rearrangements

Learning Outcomes

• Understand the structure of chromosomes and mapping methods.

• Define and explain deletion, duplication, inversion, and translocation.

• Discuss slippage, unequal crossing over, and the role of inversions as crossover suppressors.

Methods of Mapping Chromosomes

• Polytene Chromosomes: Oversized chromosomes found in Drosophila salivary glands that originated from normal chromosomes. Specific banding patterns due to enlarged regions on the chromosome.

• Fluorescent In-Situ Hybridisation (FISH): A technique utilizing fluorescent DNA probes that bind to specific regions of DNA to identify gene locations.

• Somatic Cell Hybridization: Fusion of HeLa cells with human and mouse cells using a sendai virus to create hybrid cells. Some hybrids have more human chromosomes than the other and each hybrid contains different amount of human chromosome. Selection of a known enzyme gene using a poison that only the enzyme can break down. Scientists identify which chromosomes the surviving hybrid cell has by staining and map that chromosome to the gene that codes for the specific enzyme.

• Radiation Hybrid Mapping: Chromosomes are broken into segments using X-rays and implanted into rodent cells, where they are cloned. Distant loci are more likely to be in different segments compared to close loci.

Chromosome Rearrangements and Their Consequences

• Deletion: Removal of a chromosome section. Example: In Drosophila, deletion leads to the Notch wing phenotype; in humans, Cri-du-Chat syndrome results from the loss of the tip of chromosome 5.

  • Original: $A B C * D E F$

  • After deletion: $A C * D E F$

• Duplication: Doubling of a chromosome section. Example: Can lead to gene families such as globin and odorant-receptor genes; linked to Huntington’s disease, there is also Fragile X syndrome (I read a bit about this, it’s due to repetition of CGG in the FMR1 gene in the X-chromosome, causing silencing of the gene, which is involved in neuronal development, therefore intelligence impairment), and Spinocerebellar ataxia; Bar eye duplication in Drosophila.

  • Original: $A B C * D E F$

  • After duplication: $A B B C * D E F$

  • Mis-pairing during meiosis may occur due to tandem duplication.

• Inversion: Rotation and re-insertion of a chromosome section.

  • Two types: paracentric (away from centromere) and pericetric (includes centromere)

  • Paracentric inversion results in the formation of a loop during pairing and crossing over, leading to dicentric and acentric fragments, effectively suppressing crossover due to their positions.

  • Pericentric inversion results in the formation of single-centromere chromosome with excess of one gene and deficiency of the other. Viable if small and Lethal if the inverted section is too long.

  • Drosophila example: White eye variegation and antennapedia.

• Translocation: Exchange of segments between two non-homologous chromosomes.

  • Example: $A B C * D E F$ swaps parts with $p q r s t$ leading to $A B C * D s t$ and $p q r E F$.

  • Associated with certain cancers like chronic myeloid leukemia (9-22 translocation) and Burkitt’s lymphoma (8-14 translocation).

Conclusion

Chromosomal rearrangements—deletions, duplications, inversions, and translocations—play crucial roles in genetics and can lead to significant phenotypic consequences.