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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Chromosome 21

Reviewed November 2013

What is chromosome 21?

Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 21, one copy inherited from each parent, form one of the pairs. Chromosome 21 is the smallest human chromosome, spanning about 48 million base pairs (the building blocks of DNA) and representing 1.5 to 2 percent of the total DNA in cells.

In 2000, researchers working on the Human Genome Project announced that they had determined the sequence of base pairs that make up this chromosome. Chromosome 21 was the second 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 21 likely contains 200 to 300 genes that provide instructions for making proteins. These proteins perform a variety of different roles in the body.

Genes on chromosome 21 are among the estimated 20,000 to 25,000 total genes in the human genome.

Genetics Home Reference provides information about the following genes on chromosome 21:

  • AIRE
  • APP
  • CBS
  • COL6A1
  • COL6A2
  • COL18A1
  • CSTB
  • FTCD
  • HLCS
  • ITGB2
  • KCNE1
  • KCNE2
  • MRAP
  • PCNT
  • RUNX1
  • SOD1

How are changes in chromosome 21 related to health conditions?

Many genetic conditions are related to changes in particular genes on chromosome 21. This list of disorders associated with genes on chromosome 21 provides links to additional information.

Genetics Home Reference provides information about the following conditions related to genes on chromosome 21:

  • Alzheimer disease
  • amyotrophic lateral sclerosis
  • autoimmune polyglandular syndrome, type 1
  • collagen VI-related myopathy
  • core binding factor acute myeloid leukemia
  • cytogenetically normal acute myeloid leukemia
  • familial atrial fibrillation
  • familial glucocorticoid deficiency
  • glutamate formiminotransferase deficiency
  • hereditary cerebral amyloid angiopathy
  • holocarboxylase synthetase deficiency
  • homocystinuria
  • Jervell and Lange-Nielsen syndrome
  • Knobloch syndrome
  • leukocyte adhesion deficiency type 1
  • microcephalic osteodysplastic primordial dwarfism type II
  • prostate cancer
  • rheumatoid arthritis
  • Romano-Ward syndrome
  • Unverricht-Lundborg disease

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 21.

core binding factor acute myeloid leukemia

A genetic rearrangement (translocation) involving chromosome 21 is associated with a type of blood cancer known as core binding factor acute myeloid leukemia (CBF-AML). This rearrangement occurs in approximately 7 percent of acute myeloid leukemia cases in adults. The translocation, written as t(8;21), fuses part of the RUNX1 gene from chromosome 21 with part of the RUNX1T1 gene (also known as ETO) from chromosome 8. 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 fusion protein produced from the t(8;21) translocation, called RUNX1-ETO, retains some functions of the two individual proteins. The normal RUNX1 protein, produced from the RUNX1 gene, is part of a protein complex called core binding factor (CBF) that attaches (binds) to DNA and turns on genes involved in blood cell development. The normal ETO protein, produced from the RUNX1T1 gene, turns off gene activity. The RUNX1-ETO fusion protein forms CBF and attaches to DNA, but instead of turning on genes that stimulate the development of blood cells, it turns those genes off. This change in gene activity blocks the maturation (differentiation) of blood cells and leads to the production of abnormal, immature white blood cells called myeloid blasts. While t(8;21) is important for leukemia development, one or more additional genetic changes are typically needed for the myeloid blasts to develop into cancerous leukemia cells.

Down syndrome

Down syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. This condition is most often caused by trisomy 21. Trisomy 21 means that each cell in the body has three copies of chromosome 21 instead of the usual two copies.

Less commonly, Down syndrome occurs when part of chromosome 21 becomes attached (translocated) to another chromosome during the formation of reproductive cells (eggs and sperm) or very early in fetal development. Affected people have two copies of chromosome 21 plus extra material from chromosome 21 attached to another chromosome, resulting in three copies of genetic material from chromosome 21. Affected individuals with this genetic change are said to have translocation Down syndrome.

In a very small percentage of cases, Down syndrome results from an extra copy of chromosome 21 in only some of the body's cells. In these people, the condition is called mosaic Down syndrome.

Researchers believe that having extra copies of genes on chromosome 21 disrupts the course of normal development, causing the characteristic features of Down syndrome and the increased risk of health problems associated with this condition.

other cancers

Translocations of genetic material between chromosome 21 and other chromosomes have been associated with several types of cancer. For example, acute lymphoblastic leukemia (a type of blood cancer most often diagnosed in childhood) has been associated with a translocation between chromosomes 12 and 21.

other chromosomal conditions

Other changes in the number or structure of chromosome 21 have a variety of effects on health and development. Chromosome 21 abnormalities can cause intellectual disability, delayed development, and characteristic facial features. In some cases, the signs and symptoms are similar to those of Down syndrome.

Changes involving chromosome 21 can include a missing segment of the chromosome in each cell (partial monosomy 21) and a circular structure called ring chromosome 21. A ring chromosome occurs when a chromosome breaks in two places and the ends of the chromosome arms fuse together to form a circular structure.

Is there a standard way to diagram chromosome 21?

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.

Ideogram of chromosome 21
See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about chromosome 21?

You may find the following resources about chromosome 21 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.

What glossary definitions help with understanding chromosome 21?

acute ; acute lymphoblastic leukemia ; acute myeloid leukemia ; AML ; cancer ; cell ; chromosome ; differentiation ; disability ; DNA ; gene ; genome ; human genome ; human genome project ; hypotonia ; inherited ; leukemia ; monosomy ; mosaic ; muscle tone ; mutation ; myeloid ; protein ; rearrangement ; reproductive cells ; somatic mutation ; sperm ; syndrome ; translocation ; trisomy ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


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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 healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: November 2013
Published: February 8, 2016