Chromosome 22 is a small package of DNA that holds significant importance for human health. It is the second smallest of the 22 pairs of non-sex chromosomes, or autosomes. Despite its relatively small size, this chromosome is densely packed with genes that govern a wide range of biological functions, from the immune system to the formation of the heart. Structural or sequence changes on Chromosome 22 are directly linked to numerous human diseases, making it a highly studied region of the human genome.
Defining Chromosome 22: Size, Structure, and Gene Content
The physical characteristics of Chromosome 22 demonstrate why it is considered a dense genetic hub. It spans approximately 51 million base pairs of DNA, representing between 1.5 and 2 percent of the total DNA within a human cell. Historically, it was believed to be the smallest human chromosome until sequencing revealed Chromosome 21 was slightly smaller.
This chromosome was the first human chromosome to have its complete sequence of DNA building blocks determined, announced in 1999. Sequencing revealed that Chromosome 22 likely contains between 500 and 600 protein-coding genes. Most of this gene content is concentrated on the long arm, or “q” arm, which is characterized by a high density of genes compared to other chromosomal regions.
Essential Roles in Immunity and Physical Development
The genes located on Chromosome 22 are directly involved in orchestrating two fundamental biological processes: immune defense and early physical development. The immune function is managed by the immunoglobulin lambda light chain genes (IGL), located on the long arm of the chromosome. These genes are necessary for the development of B-cells, which produce antibodies to fight off pathogens. Through a process of somatic recombination, the IGL genes recombine segments to create the vast repertoire of antibodies the body needs to neutralize millions of different foreign invaders.
In terms of physical development, a key region on the chromosome contains genes that regulate the formation of several structures originating in the embryonic pharyngeal arches. These developmental instructions guide the formation of the heart, the face, and the parathyroid glands. For instance, the genes in this area are responsible for the proper partitioning of the major arteries of the heart and the development of the palate. They also control the growth of the parathyroid glands, which regulate calcium levels in the bloodstream.
Major Syndromes Caused by Structural Variations
The consequences of Chromosome 22 irregularities often arise from large-scale structural changes, such as the loss or gain of a segment of DNA. The most common disorder is 22q11.2 deletion syndrome, historically known as DiGeorge syndrome or Velocardiofacial syndrome. This syndrome, with a prevalence estimated between 1 in 4,500 and 1 in 10,000 births, is caused by the deletion of approximately 3 million base pairs at the q11.2 region. The loss of this segment, which contains about 30 to 40 genes, leads to a highly variable set of symptoms.
Common manifestations include congenital heart defects, palatal abnormalities like cleft palate, and speech difficulties due to velopharyngeal insufficiency. The deletion also causes immune system dysfunction due to thymus underdevelopment, and low calcium levels resulting from hypoparathyroidism. Conversely, duplication of this same segment results in 22q11.2 duplication syndrome, which presents with generally milder symptoms. Another rare structural variation is Cat Eye Syndrome, caused by an extra, abnormal chromosome containing duplicated material from the short and long arms of Chromosome 22. This partial tetrasomy leads to abnormalities including coloboma (a gap in the iris), anal atresia, and heart or kidney defects.
Connection to Complex Neuropsychiatric Diseases and Cancer
Chromosome 22 is implicated in diseases arising from subtler genetic risk factors or chromosomal rearrangement. The 22q11.2 region is strongly linked to an elevated risk of developing Schizophrenia; approximately 25 percent of individuals with the deletion syndrome are diagnosed with the condition. In the general population, the link to Schizophrenia and Bipolar Disorder is attributed to the cumulative effect of multiple small genetic variations, or single-nucleotide polymorphisms, across the chromosome.
The role of Chromosome 22 in cancer is exemplified by the Philadelphia Chromosome. This is a reciprocal translocation, denoted as t(9;22), where parts of Chromosome 9 and Chromosome 22 swap places. The exchange results in a truncated Chromosome 22 that harbors a new fusion gene, BCR-ABL1. This gene codes for a protein that acts as an “always on” tyrosine kinase, causing the uncontrolled proliferation of white blood cells characteristic of Chronic Myeloid Leukemia (CML).