Aneuploidy is a genetic condition where a cell has an abnormal number of chromosomes. Human cells contain 46 chromosomes arranged in 23 pairs, but in aneuploidy, a cell has one or more extra or missing chromosomes, resulting in a total count other than 46. This condition arises from errors during cell division that lead to an incorrect distribution of chromosomes.
The Cellular Mechanism of Aneuploidy
The origin of aneuploidy is traced to errors during meiosis, the specialized cell division that produces sperm and egg cells. Meiosis involves two divisions to reduce the chromosome number by half. This ensures that when a sperm and egg unite, the resulting embryo has the correct total of 46 chromosomes.
An error called nondisjunction is the primary cause of aneuploidy. Nondisjunction is the failure of paired chromosomes to separate during one of the meiotic divisions. If this occurs during the first meiotic division, all resulting gametes will have an incorrect chromosome number; two will have an extra chromosome, and two will be missing one.
Alternatively, nondisjunction can occur during the second meiotic division. In this scenario, the first division proceeds normally, but sister chromatids fail to separate in the second. This results in two normal gametes, one gamete with an extra chromosome, and one missing a chromosome. When such a gamete is involved in fertilization, the embryo will have aneuploidy.
While associated with meiosis, nondisjunction can also happen during mitosis, the division of somatic (body) cells. When this occurs after fertilization, it leads to mosaicism, where an individual has a mixture of cells with both normal and abnormal chromosome numbers. The effects of mitotic nondisjunction depend on when and where it occurs.
Types of Aneuploidy
Aneuploidy is classified based on whether a chromosome is lost or gained, with the two main types being monosomy and trisomy. Monosomy is a condition where one chromosome from a pair is missing, leaving a single copy and a total of 45 chromosomes. Most autosomal monosomies, which involve non-sex chromosomes, are not compatible with life.
Trisomy occurs when there is an extra chromosome, resulting in three copies of a particular chromosome instead of two, for a total of 47. While many trisomies are lethal, some can result in live births. These are often associated with significant health and developmental issues.
These types are further distinguished by whether they affect autosomes or sex chromosomes (X and Y). Autosomal aneuploidies cause more severe effects because autosomes carry a large amount of genetic information required for development. Aneuploidies involving sex chromosomes are often less severe due to natural mechanisms that handle variations in X and Y chromosome numbers.
Aneuploidy-Related Conditions in Humans
Several well-known genetic conditions are direct results of aneuploidy. Down syndrome is the most recognized condition caused by a trisomy, occurring from a third copy of chromosome 21 (Trisomy 21). Individuals with Down syndrome have characteristic facial features, intellectual disability, and an increased risk for health problems like congenital heart defects.
Aneuploidy of the sex chromosomes also leads to specific conditions. Turner syndrome is a monosomy caused by a single X chromosome and the absence of a second sex chromosome (Monosomy X). This condition affects female development, often resulting in short stature and infertility.
Another common sex chromosome aneuploidy is Klinefelter syndrome. This condition occurs in males with an extra X chromosome (XXY). Individuals with Klinefelter syndrome may have taller stature, smaller testes, and reduced testosterone production, which can affect fertility and secondary sexual characteristics.
Detection and Associated Risk Factors
Aneuploidy is detected during pregnancy using prenatal screening and diagnostic tests. Non-invasive prenatal screening (NIPS), also called NIPT, is a sensitive screening method. It analyzes fetal DNA from the pregnant person’s blood to assess the risk for common trisomies like Down syndrome.
If screening indicates a high risk, diagnostic tests like amniocentesis or chorionic villus sampling (CVS) are recommended. Amniocentesis involves sampling the amniotic fluid, while CVS samples tissue from the placenta. Both procedures directly analyze the fetal chromosomes for a conclusive diagnosis.
A primary risk factor for aneuploidy is advanced maternal age. A female’s eggs are formed during her own fetal development and remain in suspended cell division for years. As these eggs age, the cellular machinery controlling chromosome separation can become less efficient, increasing the likelihood of nondisjunction.
Aneuploidy in Somatic Cells
Aneuploidy is not exclusively a condition present from conception; it can also arise in somatic (body) cells during a person’s life due to errors in mitosis. This acquired aneuploidy is not inherited but is a well-established characteristic of many types of cancer. A large percentage of solid tumors are composed of aneuploid cells. This chromosomal instability can contribute to cancer development by disrupting genes that control cell growth and division, giving cancerous cells a survival advantage.