What Is Aneuploidy? Causes, Types, and Implications

Aneuploidy describes a condition where a cell has an abnormal number of chromosomes, meaning there is either an extra or a missing chromosome, differing from the typical count for a species. Humans normally have 46 chromosomes, arranged in 23 pairs within each cell. These thread-like structures, found in the cell nucleus, are composed of DNA tightly coiled around proteins. This DNA contains the genetic instructions essential for an organism’s development, functioning, and reproduction.

How Aneuploidy Arises

Aneuploidy primarily results from nondisjunction, the failure of chromosomes to separate properly during cell division. This error often occurs during meiosis, the specialized cell division that produces egg and sperm cells (gametes). Normally, during meiosis, chromosome pairs or sister chromatids divide equally, ensuring each gamete receives a single set of 23 chromosomes.

Nondisjunction can happen in two main stages of meiosis. In Meiosis I, homologous chromosome pairs may fail to separate, leading to gametes with an extra or missing chromosome. In Meiosis II, sister chromatids may not separate, resulting in some gametes with a normal count and others with an extra or missing chromosome. If an abnormal gamete participates in fertilization, the resulting embryo will have an aneuploid chromosome number.

Forms of Aneuploidy and Key Examples

Aneuploidy manifests most commonly as trisomy or monosomy. Trisomy describes the presence of an extra copy of a chromosome, meaning three copies instead of the usual two. For instance, Trisomy 21, also known as Down syndrome, occurs when an individual has three copies of chromosome 21. Other examples include Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome), involving an extra copy of chromosome 18 and 13, respectively. Sex chromosome trisomies can also occur, such as XXY (Klinefelter syndrome) with an extra X chromosome, or XYY syndrome with an extra Y chromosome.

Monosomy refers to the absence of one chromosome from a pair, resulting in only one copy instead of two. The most recognized example is Monosomy X, also known as Turner syndrome. In this condition, individuals have only one X chromosome instead of the typical two sex chromosomes (XX or XY).

General Implications

An incorrect number of chromosomes often has significant consequences for an individual’s development and overall health. This can disrupt the delicate balance of gene expression, affecting cellular processes and organ formation. Many aneuploidies are incompatible with life, leading to spontaneous miscarriage.

The severity and specific effects of aneuploidy largely depend on which chromosome is affected and whether it is a gain or loss. Aneuploidies involving larger chromosomes or those with a higher density of genes tend to have more severe outcomes. While some aneuploidies are associated with distinct syndromes and developmental challenges, others may result in early embryonic loss.

Identifying Aneuploidy and Associated Factors

Aneuploidy can be identified through various genetic testing methods. Karyotyping, a traditional technique, involves examining a person’s chromosomes under a microscope to visualize their number and structure. More modern approaches include non-invasive prenatal testing (NIPT), which analyzes fetal DNA fragments circulating in the mother’s blood to screen for common aneuploidies. For a definitive diagnosis during pregnancy, invasive procedures like amniocentesis or chorionic villus sampling (CVS) can obtain fetal cells for chromosomal analysis.

Advanced maternal age is a primary factor associated with an increased likelihood of aneuploidy, especially for trisomies. As a woman ages, the eggs stored in her ovaries also age, potentially leading to errors in chromosome segregation during meiosis. While less common, advanced paternal age may also contribute to a minor increase in aneuploidy risk. Genetic counseling and testing options are important for individuals concerned about aneuploidy.