CD

Lecture_21_Chromosome_Rearrangement

Overview of Chromosome Rearrangements

  • Focus on types of chromosomal rearrangements and their impact on genetic information.

  • Key concepts: viability of gametes, information loss, and gene balance.

Chromosomal Rearrangements

  • Definition: Changes in the structure of chromosomes that can involve breaks and reattachments of DNA strands.

  • Mechanisms: Require double-stranded DNA breaks; involve non-homologous end joining or homologous recombination for repair (RAD51 complex).

Types of Genetic Rearrangements

  1. Balanced Rearrangements

    • No net loss or gain of genetic material.

    • Examples: Inversions and translocations.

    • Inversions: Segments of a chromosome are flipped. Example:

      • From ABCD to ACBD.

      • Generally silent if gene reading and function remain intact.

    • Translocations: Segments are exchanged between non-homologous chromosomes without loss of genetic information.

  2. Imbalanced Rearrangements

    • Result in the gain or loss of genetic material, affecting viability.

    • Consequence: Can lead to lethal gametes if essential information is lost.

Inversion Types

  • Paracentric Inversions: Do not include centromere.

    • Example scenario: Loss of acentric fragments during meiosis causes lethal gametes.

  • Pericentric Inversions: Involve centromere.

    • Genetic material can still be pulled into gametes but may lead to imbalance issues in offspring.

Mechanisms of Inversions

  • Inversion Loops: Necessary for homologous chromosomes to pair during meiosis.

  • Inversions can lead to changes in crossover events, affecting recombinant viability.

  • Crossover in the presence of inversion loops can result in:

    1. Normal gametes (if proper genetic balance is maintained).

    2. Non-viable gametes (if crucial genes are disrupted).

Translocations

  • Definition: The transfer of segments between chromosomes, maintaining genetic balance if the entirety of gene information persists.

    • Alternate Segregation: Results in viable gametes (normal segregation of chromosomes).

    • Adjacent Segregation: Leads to non-viable gametes (genetic imbalance).

    • Robertsonian Translocation: Specific case related to Down syndrome, involving chromosome 14 and 21; results in trisomy due to fusion of chromosome segments.

Deletions and Duplications of Genes

  • Deletions: Loss of genetic information can lead to severe phenotypic effects depending on the genes lost.

    • Intragenic Deletions: Affect genes directly, leading to loss of function.

  • Duplications: Gain extra copies of genes can also lead to imbalances and phenotypic severity based on gene dosage effect.

Potential Outcomes of Chromosomal Changes

  • Viable or lethal gametes based on balance and gene representation.

  • Expression of recessive alleles in the absence of dominant partners leading to pseudodominance.

  • Key examples of severe phenotypic effects include Krütschav syndrome from deletions.

Summary

  • Chromosomal changes can broadly categorise into balanced and imbalanced rearrangements, impacting the viability of gametes and overall phenotypic expression.

  • Understanding the specifics of inversions, translocations, and other rearrangements is essential for grasping genetic inheritance patterns.