Reviewed May 2012
What is chromosome 22?
Humans normally have 46 chromosomes (23 pairs) in each cell. Two copies of chromosome 22, one copy inherited from each parent, form one of the pairs. Chromosome 22 is the second smallest human chromosome, spanning more than 51 million DNA building blocks (base pairs) and representing between 1.5 and 2 percent of the total DNA in cells.
In 1999, researchers working on the Human Genome Project announced they had determined the sequence of base pairs that make up this chromosome. Chromosome 22 was the first human chromosome to be fully sequenced.
Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 22 likely contains 500 to 600 genes that provide instructions for making proteins. These proteins perform a variety of different roles in the body.
Genes on chromosome 22 are among the estimated 20,000 to 25,000 total genes in the human genome.
How are changes in chromosome 22 related to health conditions?
Many genetic conditions are related to changes in particular genes on chromosome 22.
This list of disorders associated with genes on chromosome 22 provides links to additional information.
Changes in the structure or number of copies of a chromosome can also cause problems with health and development. The following chromosomal conditions are associated with such changes in chromosome 22.
22q11.2 deletion syndrome
Most people with 22q11.2 deletion syndrome are missing about 3 million base pairs on one copy of chromosome 22 in each cell. The deletion occurs near the middle of the chromosome at a location designated as q11.2. This region contains 30 to 40 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region.
The loss of a particular gene, TBX1, is thought to be responsible for many of the characteristic features of 22q11.2 deletion syndrome such as heart defects, an opening in the roof of the mouth (a cleft palate), distinctive facial features, and low calcium levels. Some studies suggest that a deletion of this gene may contribute to behavioral problems as well. The loss of another gene, COMT, in the same region of chromosome 22 may also help explain the increased risk of behavioral problems and mental illness. Additional genes in the deleted region likely contribute to the varied signs and symptoms of 22q11.2 deletion syndrome.
22q13.3 deletion syndrome
22q13.3 deletion syndrome, which is also commonly known as Phelan-McDermid syndrome, is caused by a deletion near the end of the long (q) arm of chromosome 22. A ring chromosome 22 can also cause 22q13.3 deletion syndrome. A ring chromosome is a circular structure that occurs when a chromosome breaks in two places, the tips of the chromosome are lost, and the broken ends fuse together. People with ring chromosome 22 have one copy of this abnormal chromosome in some or all of their cells. Researchers believe that several critical genes near the end of the long (q) arm of chromosome 22 are lost when the ring chromosome 22 forms. If the break point on the long arm is at chromosome position 22q13.3, people with ring chromosome 22 will experience similar signs and symptoms as those with a simple deletion.
The signs and symptoms of 22q13.3 deletion syndrome are probably related to the loss of multiple genes at the end of chromosome 22. The size of the deletion varies among affected individuals. The loss of a particular gene, SHANK3, is thought to be responsible for many of the characteristic features of 22q13.3 deletion syndrome, such as developmental delay, intellectual disability, and absent or severely delayed speech. Additional genes in the deleted region likely contribute to the signs and symptoms of 22q13.3 deletion syndrome.
A rearrangement (translocation) of genetic material between chromosomes 17 and 22, written as t(17;22), causes a rare type of skin cancer known as dermatofibrosarcoma protuberans. This translocation fuses part of the PDGFB gene from chromosome 22 with part of the COL1A1 gene from chromosome 17. The translocation is found on one or more extra chromosomes that can be either linear or circular. When circular, the extra chromosomes are known as supernumerary ring chromosomes. This mutation is acquired during a person's lifetime and is present only in certain cells. This type of genetic change, called a somatic mutation, is not inherited.
The fused COL1A1-PDGFB gene provides instructions for making a combined (fusion) protein that researchers believe ultimately functions like the active PDGFB protein. In the translocation, the PDGFB gene loses the part of its DNA that limits its activity, and production of the COL1A1-PDGFB fusion protein is controlled by COL1A1 gene sequences. As a result, the gene fusion leads to the production of a larger amount of active PDGFB protein than normal. Active PDGFB protein signals for cell growth and division (proliferation) and maturation (differentiation). Excess PDGFB protein abnormally stimulates cells to proliferate and differentiate, leading to the tumor formation seen in dermatofibrosarcoma protuberans.
22q11.2 duplication is caused by an extra copy of some genetic material at position q11.2 on chromosome 22. In most cases, this extra genetic material consists of a sequence of about 3 million DNA building blocks (base pairs), also written as 3 megabases (Mb). This sequence is the same one that is missing in 22q11.2 deletion syndrome. A small percentage of affected individuals have a shorter duplication in the same region. The duplication affects one of the two copies of chromosome 22 in each cell. Researchers are working to determine the genes that may contribute to the developmental delay and other problems that affect some people with this duplication.
Emanuel syndrome is caused by the presence of extra genetic material from chromosome 11 and chromosome 22 in each cell. In addition to the usual 46 chromosomes, people with Emanuel syndrome have an extra (supernumerary) chromosome consisting of a piece of chromosome 11 attached to a piece of chromosome 22. The extra chromosome is known as a derivative 22 or der(22) chromosome.
People with Emanuel syndrome typically inherit the der(22) chromosome from an unaffected parent. The parent carries a chromosomal rearrangement between chromosomes 11 and 22 called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. As this translocation is passed to the next generation, it can become unbalanced. Individuals with Emanuel syndrome inherit an unbalanced translocation between chromosomes 11 and 22 in the form of a der(22) chromosome. These individuals have two normal copies of chromosome 11, two normal copies of chromosome 22, and extra genetic material from the der(22) chromosome.
As a result of the extra chromosome, people with Emanuel syndrome have three copies of some genes in each cell instead of the usual two copies. The excess genetic material disrupts the normal course of development, leading to intellectual disability and birth defects. Researchers are working to determine which genes are included on the der(22) chromosome and what role these genes play in development.
Translocations involving chromosome 22 are also involved in a type of cancerous tumor known as Ewing sarcoma. These tumors develop in the bones or soft tissues, such as cartilage and nerves. The most common translocation, t(11;22), fuses part of the EWSR1 gene from chromosome 22 with part of the FLI1 gene from chromosome 11, creating the EWSR1/FLI1 fusion gene. Translocations that fuse the EWSR1 gene with other genes that are related to the FLI1 gene can also cause Ewing sarcomas, although these alternative translocations are relatively uncommon. The mutations that cause these cancers are acquired during a person's lifetime and are present only in tumor cells. This type of genetic change, called a somatic mutation, is not inherited.
The protein produced from the EWSR1/FLI1 fusion gene, called EWS/FLI, has functions of the protein products of both genes. The FLI protein, produced from the FLI1 gene, attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. The FLI protein controls the growth and development of some cell types by regulating the transcription of certain genes. The EWS protein, produced from the EWSR1 gene, also regulates transcription. The EWS/FLI protein has the DNA-binding function of the FLI protein as well as the transcription regulation function of the EWS protein. It is thought that the EWS/FLI protein turns the transcription of a variety of genes on and off abnormally. This dysregulation of transcription leads to uncontrolled growth and division (proliferation) and abnormal maturation and survival of cells, causing tumor development.
Opitz G/BBB syndrome
The autosomal dominant form of Opitz G/BBB syndrome is caused by a deletion in one copy of chromosome 22 in each cell. This condition is considered part of 22q11.2 deletion syndrome because affected people usually have a deletion in the same region of chromosome 22. These cases occur in people with no history of the disorder in their family. It is not yet known which deleted gene(s) cause the signs and symptoms of Opitz G/BBB syndrome.
- other cancers
Several types of blood cancer known as leukemias are associated with a translocation of genetic material between chromosomes 9 and 22. This chromosomal abnormality, which is commonly called the Philadelphia chromosome, is found only in cancer cells. The translocation that results in the Philadelphia chromosome is somatic, which means it is acquired during a person's lifetime. This translocation fuses part of a specific gene from chromosome 22 (the BCR gene) with part of another gene from chromosome 9 (the ABL1 gene). The protein produced from this fused gene abnormally signals tumor cells to continue dividing and prevents them from adequately repairing DNA damage.
The Philadelphia chromosome has been identified in most cases of a slowly progressing form of blood cancer called chronic myeloid leukemia (CML). It also has been found in some cases of more rapidly progressing blood cancers known as acute leukemias. The presence of the Philadelphia chromosome can help predict how a cancer will progress and provides a target for molecular therapies.
- other chromosomal conditions
Other changes in the number or structure of chromosome 22 can have a variety of effects. Intellectual disability, delayed development, delayed or absent speech, distinctive facial features, and behavioral problems are common features. Frequent changes to chromosome 22 include an extra piece of the chromosome in each cell (partial trisomy), a missing segment of the chromosome in each cell (partial monosomy), and a ring chromosome 22. Rearrangements (translocations) of genetic material between chromosomes can also lead to extra or missing material from chromosome 22. The most common of these translocations involves chromosomes 11 and 22.
Cat-eye syndrome is a rare disorder most often caused by a chromosomal change called an inverted duplicated 22. In people with this condition, each cell has at least one small extra chromosome made up of genetic material from chromosome 22 that has been abnormally copied (duplicated). The extra genetic material causes the characteristic signs and symptoms of cat-eye syndrome, including an eye abnormality called an iris coloboma (a gap or split in the colored part of the eye), small skin tags or pits in front of the ear, unusually formed ears, heart defects, kidney problems, malformations of the anus, and, in some cases, delayed development.
Is there a standard way to diagram chromosome 22?
Geneticists use diagrams called ideograms as a standard representation for chromosomes. Ideograms show a chromosome's relative size and its banding pattern. A banding pattern is the characteristic pattern of dark and light bands that appears when a chromosome is stained with a chemical solution and then viewed under a microscope. These bands are used to describe the location of genes on each chromosome.
Where can I find additional information about chromosome 22?
You may find the following resources about chromosome 22 helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
Where can I find general information about chromosomes?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding chromosome 22?
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? in the Handbook.