Human cells contain packages of genetic information called chromosomes. These structures, made of DNA tightly coiled around proteins, serve as the instruction manuals for building and operating the body. Humans have 23 pairs of these chromosomes in each cell, for a total of 46. The first 22 pairs are known as autosomes, while the 23rd pair determines sex.
Each pair is numbered, and chromosome 21 is one of these pairs, with one copy inherited from each parent. Like every other chromosome, it carries a specific set of genes that provide the blueprints for various bodily processes.
The Biological Role of Chromosome 21
Chromosome 21 is the smallest human autosome, representing about 1.5 to 2 percent of the total DNA within a cell. Despite its small size, it is estimated to contain between 200 and 300 genes. Researchers fully sequenced the base pairs that make up this chromosome in 2000, making it the second human chromosome to be completely mapped.
The genes on chromosome 21 provide instructions for producing proteins involved in a wide range of biological activities. For instance, some genes on this chromosome play a part in regulating the immune system, while others are involved in skeletal muscle growth and communication between nerve cells.
Trisomy 21 and Down Syndrome
The most common condition related to chromosome 21 is Trisomy 21, the presence of three copies of this chromosome instead of the usual two. This additional genetic material disrupts the normal course of development, leading to the characteristics associated with Down syndrome. About 95% of people with Down syndrome have Trisomy 21, where the third copy leads to an overexpression of the genes it contains, which in turn alters developmental pathways.
This chromosomal alteration most often occurs due to a random error in cell division called nondisjunction. During the formation of reproductive cells—either sperm or, more commonly, eggs—the pair of chromosome 21s fails to separate properly. As a result, a reproductive cell ends up with two copies of chromosome 21 instead of one. When this cell is part of fertilization, the resulting embryo has three copies of chromosome 21 in every cell. This event is not typically inherited and is not associated with anything the parents did before or during pregnancy.
Individuals with Down syndrome may have certain physical traits, such as a flattened facial profile, upward-slanting eyes, and a single deep crease across the palm of the hand. Development may also be affected, with many individuals experiencing some degree of intellectual disability and delays in reaching milestones like learning to speak. People with this condition may also have an increased likelihood of certain health issues, including congenital heart defects and hearing loss.
Variations in Chromosome 21 Abnormalities
Beyond Trisomy 21, there are other, less frequent genetic variations. One is Mosaic Down syndrome, which accounts for about 2% of cases. In this situation, the nondisjunction event happens after fertilization, resulting in a mixture of cells—some with the typical 46 chromosomes and others with 47. Because only a percentage of cells are affected, individuals with mosaicism may have fewer of the typical characteristics of Down syndrome.
Another variation is Translocation Down syndrome, making up about 3% of cases. Here, the total number of chromosomes remains 46, but a full or partial extra copy of chromosome 21 is attached to another chromosome, often chromosome 14. Unlike Trisomy 21, which is a random event, this translocation can be inherited from a parent who carries a “balanced” rearrangement without any health effects.
A much rarer condition is Monosomy 21, where an individual has only one copy of chromosome 21 instead of the usual two. This loss of genetic material can lead to significant health and developmental effects.
Prenatal Testing Methods
During pregnancy, tests are available to detect potential chromosomal abnormalities. These methods fall into two main categories: screening tests and diagnostic tests.
Screening tests estimate the probability or chance that a fetus has a particular condition. One common screening method is noninvasive prenatal testing (NIPT), which analyzes small fragments of fetal DNA present in the mother’s bloodstream to assess the likelihood of conditions like Trisomy 21. These tests are noninvasive but do not provide a definitive answer; instead, they indicate if further testing is warranted.
Diagnostic tests are used to confirm a diagnosis with a high degree of accuracy. Procedures like amniocentesis and chorionic villus sampling (CVS) are considered diagnostic. Amniocentesis involves taking a small sample of the amniotic fluid, while CVS takes a tissue sample from the placenta. Both procedures carry a small risk but can definitively identify chromosomal abnormalities by directly analyzing the fetus’s genetic material.