Chromosome 21: What is it? History, Anatomy and Down Syndrome

Appearance at the chromosomal level can reveal the specific genes behind certain traits and disorders, while providing information about the organization of the genome.

The presentation of the DNA sequences of human chromosomes represents a new chapter in the history of developing genomics, but one with roots in the half-century-old field of cytogenetics.

The tiny chromosome 21, the smallest in humans, despite its number as the penultimate, is the fourth to be described.

Chromosome 21 is a chromosome with a familiarity factor, in the form of Down syndrome, usually caused by an extra copy of the chromosome.

Chromosome 21 sequencing provides a powerful new tool for ongoing investigation of the causes and components of Down syndrome.

This is the most commonly observed aberration of a non-sex chromosome, presumably because it involves the fewest number of genes.

Therefore, it is less severe than having extra copies of other autosomes, which drastically deflects the development that typically leads to miscarriage.


Down syndrome takes its name from Sir John Langdon Haydon Down, a medical superintendent at a center for the profoundly mentally retarded.

In 1886, it was given the term “Mongolism” to denote 10 percent of patients with distinctive facial features.

The chromosomal connection came later.

In 1914, Theodor Boveri, professor of zoology at the University of Wurzburg, suggested that abnormal numbers or structures of chromosomes could be associated with specific syndromes.

The abnormal chromosome number linkage syndrome was suggested as early as 1932, although researchers were not able to clearly visualize an extra small chromosome in patients’ cells until 1958.

The identification of the extra chromosome in Down syndrome as number 21 occurred in 1959.

This was a watershed moment in cytogenetics, the field that combines chromosomal variants with traits or disorders.

Improved microscopy and staining techniques allowed researchers to move from a chromosome clustering system to a few size-based clusters to order individually.

Cytogenetists developed increasingly specific DNA stains and probes to highlight and distinguish chromosomes, revealing the guides that would help anchor linkage data to build the first genetic maps.

Some of these techniques estimated the density of genes that genome sequencing today addresses directly. Many R bands mean, broadly speaking, many genes. But chromosome 21 is so small that it produces a not very significant R band.

The rise of positional cloning in the 1980s gradually allowed researchers to complete chromosome maps.

The 33.5 million bases, which make up 97 percent of the long arm of chromosome 22, with 11 spaces.

They introduced 545 genes that code for proteins and 134 pseudogenes, which are sequences very similar to those of active but not expressed genes, as genetic graveyards.

Chromosome 22 contains genes for schizophrenia, chronic myeloid leukemia, cardiovascular disease, and DiGeorge syndrome .

Its high gene density is consistent with long-standing estimates that the entire genome has at least 80,000 genes that code for proteins.

Chromosome 21 anatomy

In general, chromosome 21 has typical characteristics: repeating DNA sequences at the tips and in the centromere, and genes encoding proteins scattered along its long arm.

Sequencing of 33,546,361 base pairs revealed 225 protein-encoding genes, including 127 known genes and 98 genes predicted from computerized sequence analysis, plus 59 pseudogenes.

Known genes encode signaling proteins, cell adhesion molecules, transcription factors, and ion channels.

Disease-causing genes include those for the beta-amyloid form of Alzheimer’s disease, susceptibility to bipolar affective disorder; and forms of epilepsy, hearing loss, leukemia, and hyperlipidemia.

Number 21 is also riddled with duplications and other repetitions.

A 93-base sequence occurs in 10 copies and also on other chromosomes, and a six-base sequence is repeated 17 times.

A seven-million-base stretch harbors only one protein-encoding gene, and three million-base areas lack genes.

Combined, these “black holes” represent one third of the chromosome.

Several lines of evidence had led geneticists to expect chromosome 21 to be light as the gene, but perhaps not as light as the sequence revealed.

Down syndrome

Chromosome 21 spans about 47 million base pairs (the building blocks of DNA) and represents about 1.5 percent of the total DNA in cells.

The critical region for the development of Down syndrome has been assigned to a small segment of the long arm (21q).

The most common forms of chromosome change in Down syndrome are:

  • Nondisjunction arose during the first meiotic division of gametogenesis (95% of cases); the incidence increases dramatically with maternal age, from 1 in 1000 during the first years of reproduction to 1 in 30 at 45 years.
  • Translocation of an extra long arm of chromosome 21 to another chromosome (5% of cases).

Trisomy of human chromosome 21 is the genetic basis for Down syndrome.

This is a prototypical neurodevelopmental disorder associated with a spectrum of developmental disabilities.

The tripling of an entire human chromosome has made basic research on underlying molecular genetics, cell biology, and neuropathology very difficult .

These have allowed the identification of critical chromosomal regions and specific genes that underlie the neurological and non-neurological aspects of Down syndrome.

Such findings are expected to culminate in novel therapies that will improve impaired cognition and neurodegeneration seen in many individuals with Down syndrome.