What role does non-disjunction play in causing Down syndrome and other chromosomal abnormalities?
What role does non-disjunction play in causing Down syndrome and other chromosomal abnormalities?
Answered
Nondisjunction is a critical error in cell division that plays a significant role in causing Down syndrome and various other chromosomal abnormalities. Here’s how nondisjunction contributes to these conditions:
What is Nondisjunction?
Nondisjunction occurs when homologous chromosomes or sister chromatids fail to separate properly during meiosis, leading to gametes with an abnormal number of chromosomes. This can happen during either meiosis I or meiosis II:
- Meiosis I: If homologous chromosomes do not separate, two gametes will receive an extra chromosome (n+1), and two will be missing one chromosome (n-1).
- Meiosis II: If sister chromatids fail to separate, one gamete will have two copies of a chromosome (n+1), one will have none (n-1), and two will have the normal number (n).
When these abnormal gametes fuse with normal gametes during fertilization, they result in zygotes with aneuploidy—an abnormal number of chromosomes.
Role in Down Syndrome
Trisomy 21
Down syndrome, or Trisomy 21, is primarily caused by nondisjunction:
- Mechanism: In approximately 95% of cases, nondisjunction occurs during maternal meiosis, leading to an egg with two copies of chromosome 21. When this egg is fertilized by a normal sperm (with one copy of chromosome 21), the resulting zygote has three copies of chromosome 21 instead of the usual two, resulting in a total of 47 chromosomes.
- Clinical Features: Individuals with Down syndrome exhibit characteristic features such as intellectual disability, distinct facial features, and increased risk for certain health issues due to the presence of an extra copy of genes on chromosome 21.
Other Forms of Down Syndrome
- Mosaic Down Syndrome: This occurs when nondisjunction happens after fertilization. Some cells have the typical 46 chromosomes while others have 47 due to the extra chromosome 21. This can lead to milder symptoms compared to standard Trisomy 21.
- Translocation Down Syndrome: In about 4% of cases, part of chromosome 21 attaches to another chromosome (often chromosome 14) during cell division. The total number of chromosomes remains 46, but the genetic material from chromosome 21 is present in excess, leading to Down syndrome characteristics.
Other Chromosomal Abnormalities Due to Nondisjunction
Nondisjunction can also lead to other chromosomal disorders:
- Patau Syndrome (Trisomy 13) and Edwards Syndrome (Trisomy 18): Both conditions arise from the presence of an extra chromosome due to nondisjunction during meiosis. These conditions are often associated with severe developmental issues and reduced life expectancy.
- Klinefelter Syndrome (XXY) and Turner Syndrome (XO): These are examples of sex chromosome aneuploidies caused by nondisjunction. Klinefelter syndrome results from an extra X chromosome in males, while Turner syndrome results from the absence of one X chromosome in females
BNO Team