Aneuploidy is a condition defined by the presence of an abnormal number of chromosomes within a cell. Human cells contain 46 chromosomes organized into 23 pairs, and in cases of aneuploidy, cells have one or more extra or missing chromosomes. This imbalance can be compared to an instruction manual for the body with a missing or extra page, leading to disruptions in development and function. The consequences of this imbalance depend on which chromosomes are involved. This condition is a cause of many genetic disorders, and some cancer cells also exhibit an abnormal number of chromosomes.
The Cellular Mechanisms of Aneuploidy
Aneuploidy most often originates from errors during meiosis, the specialized cell division process that produces sperm and egg cells. This process is designed to reduce the chromosome number by half, so that when a sperm and egg unite, the resulting embryo has the correct total of 46 chromosomes. The primary cause of aneuploidy is an event called nondisjunction, which is the failure of chromosome pairs to separate correctly during meiosis.
In the first stage of meiosis, homologous chromosomes are supposed to separate. If they fail to do so, both chromosomes from the pair can be pulled into one daughter cell, leaving the other with no chromosome from that pair. An error can also occur in the second meiotic division when sister chromatids fail to separate. Either case results in a sperm or egg cell with an extra or a missing chromosome.
If one of these aneuploid reproductive cells is involved in fertilization, the resulting embryo will also be aneuploid, carrying the incorrect chromosome number in every cell. While nondisjunction in meiosis is a common source of congenital conditions, similar errors can happen during mitosis, the cell division for growth and repair. Mitotic nondisjunction creates mosaicism, where an individual has a mixture of cells—some with the normal number of chromosomes and others that are aneuploid.
The risk of meiotic nondisjunction, particularly in egg cells, increases with maternal age. Female egg cells are formed at birth and remain suspended in an early stage of meiosis for decades. Researchers believe the cellular structures that control chromosome separation may degrade over time, making older eggs more susceptible to nondisjunction events.
Common Aneuploid Conditions
Aneuploid conditions are categorized into two main types: trisomy, which is the presence of an extra chromosome, and monosomy, the absence of a chromosome. The majority of aneuploidies are not compatible with life and result in miscarriage. However, a few specific aneuploidies can result in a live birth, leading to well-documented genetic syndromes.
The most recognized trisomic condition is Down syndrome, or Trisomy 21, which occurs when an individual has three copies of chromosome 21 instead of two. Other less common but severe trisomies include Edwards syndrome (Trisomy 18) and Patau syndrome (Trisomy 13). Edwards syndrome is associated with significant developmental delays, and Patau syndrome causes severe intellectual disability and physical abnormalities of the heart, brain, and kidneys.
In cases of monosomy, the most common condition compatible with life is Turner syndrome, which affects individuals assigned female at birth. This condition, also called Monosomy X, occurs when one of the two X sex chromosomes is missing. Most other monosomies involving the non-sex chromosomes (autosomes) are lethal. The presence of an extra chromosome, as in trisomies, is better tolerated than the loss of one, which may explain why more trisomic conditions result in live births.
Prenatal and Postnatal Diagnosis
The detection of aneuploidy can occur both before and after birth through a combination of screening and diagnostic tests. Prenatal screening is designed to assess the probability of a fetus having a specific aneuploidy but does not provide a definitive answer. The most common screening method is non-invasive prenatal testing (NIPT), which analyzes fetal DNA circulating in the pregnant person’s bloodstream. NIPT can screen for common trisomies like Down syndrome, but a positive result requires confirmation.
For a definitive diagnosis, invasive tests are necessary to collect fetal cells for analysis. Chorionic villus sampling (CVS) is performed between 10 and 14 weeks of gestation and involves taking a small sample of tissue from the placenta. Amniocentesis is another diagnostic option, performed after 15 weeks, where a sample of amniotic fluid containing fetal cells is collected. Both procedures carry a small risk but provide the cells needed for a definitive analysis.
The collected fetal cells are then used to create a karyotype, which is a visual map of the chromosomes. By arranging the chromosomes in pairs and in order of size, technicians can count them and identify any numerical abnormalities, confirming a diagnosis of aneuploidy. If an aneuploid condition is not detected before birth, a postnatal diagnosis can be made from a newborn’s blood sample by performing a karyotype analysis.
Aneuploidy Beyond Congenital Disorders
While aneuploidy is often discussed in the context of congenital conditions, it is not limited to disorders present at birth. Aneuploidy also occurs in somatic cells—the cells that make up the body’s tissues and organs—throughout an individual’s life. These changes, resulting from errors in mitosis, are known as somatic aneuploidy and are a hallmark of many types of cancer.
In cancer cells, having an unstable genome with an incorrect number of chromosomes is common. This chromosomal instability can contribute to tumor development by disrupting the balance of genes that regulate cell growth. The loss of a chromosome might remove a tumor-suppressing gene, while the gain of another could amplify a cancer-promoting gene, providing the cell with a growth advantage.
Somatic aneuploidy also appears to increase with age in otherwise healthy tissues, including the brain and liver. Research has shown an age-related accumulation of aneuploid cells in various tissues. The precise role of this age-related aneuploidy is still under investigation, but it is thought to be linked to tissue degeneration and some aspects of the aging process. This demonstrates that aneuploidy is a broad biological phenomenon with implications extending far beyond early development.