lecture 18 Chromosomal Abnormalities

Chromosomal Abnormalities Overview

• Chromatin and Chromosome Structure

  • Chromatin exists in a 30-nm fiber or more condensed state during interphase.

• Types of Chromosomal Abnormalities

  1. Variations in Chromosomal Number

  • Aneuploidy: Change in the number of chromosomes (missing or added).

  • Polyploidy: More than two sets of chromosomes (e.g., 3n, 4n).

  1. Changes to Chromosomal Structure

     unequal crossover causes chromosomal rearrangement.

  • Deletions: Loss of chromosomal segments.

  • Duplications: a chromosome segment is copied, resulting in extra copies of that region.

  • Inversions: A segment of a chromosome is flipped and reinserted in the reverse orientation.

    • Paracentric: centromere is outside of the inverted region.

      • Crossing over results in two normal gametes and a dicentric chromosome (breaks) and an acentric fragment (lost).

    • Pericentric: centromere is within the inverted region.

      • crossing over results in two normal gametes and two abnormal gametes

  • Translocations: A piece of one chromosome breaks off and attaches to a non-homologous chromosome.

    • Nonreciprocal translocations: A piece of one chromosome moves to another chromosome without any equivalent exchange. .

    • Reciprocal balanced translocations: Two non-homologous chromosome pieces switch places.

    • Robertsonian Chromosome Translocations: chromosome fusion, fusion of two nonhologous chromosomes.

Chromatin Types

• Constitutive Heterochromatin

  • Always transcriptionally inactive.

  • Examples: telomeric DNA and centromeric DNA.

• Facultative Heterochromatin

  • Can switch between heterochromatin and euchromatin.

  • Example: Barr body (inactivated X chromosome and females).

Nondisjunction and Meiosis

• Nondisjunction: Failure of chromosomes to separate properly during meiosis, leading to aneuploidy.

  • Can occur in Meiosis I or Meiosis II.

  • Results in gametes with either $n + 1$ (trisonomy) or $n - 1$ (monosomy).

Consequences of Gene Dosage Changes

• Changes in gene dosage (number of copies) can lead to imbalances in gene products:

  • In animals, often results in severe abnormalities due to reduced fertility.

Types of Aneuploidy

• Monosomy: Loss of a single chromosome (2n-1).

• Trisomy: Addition of a single chromosome (2n+1).

• Nullisomy: Loss of a homologous chromosome pair (2n-2).

• Tetrasomy: Addition of two homologous chromosomes (2n+2).

Aneuploidy in Humans

• Humans have very few viable aneuploidies:

  • Only notable trisomies:

  • Trisomy 13: Patau Syndrome

  • Trisomy 18: Edwards Syndrome

  • Trisomy 21: Down Syndrome

  • Sex Chromosome Aneuploidies:

  • Klinefelter syndrome (XXY)

  • Turner syndrome (XO)

Risk of Down Syndrome by Maternal Age

• Increased maternal age correlates with higher risk of trisomy 21 (Down syndrome):

Turner Syndrome

• Characteristics:

  • Monosomy of X chromosome (XO)

  • Symptoms: Short stature, infertility, webbed neck.

• Cause: Insufficient levels of gene SHOX lead to developmental issues.

Polyploidy

• Definition: Presence of three or more sets of chromosomes.

• Can be caused by:

  • Autopolyploidy: Duplication within a species.

  • Allopolyploidy: Combination of sets from different species.

Consequences of Polyploidy

• Polyploids can exhibit:

  1. Increased fruit and flower size.

  2. Decreased fertility, especially in odd-numbered polyploids.

  3. Hybrid vigor, improving growth, yield, and disease resistance.

Chromosomal Rearrangements

• Deletions, Duplications, Inversions, Translocations can alter genetic information.

• Unequal Crossover can lead to deletions or duplications, which may cause syndromes like Williams-Beuren syndrome.

Summary

• Aneuploidy: Variation in chromosome number (gaining/loss of chromosomes).

• Polyploidy: More than two sets of chromosomes.

• Understanding chromosomal abnormalities is crucial for comprehending their effects on health and development.