Chromosome 21 Explained

Length Bp:	45,090,682 bp (CHM13)
Genes:	215 (CCDS)
Type:	Autosome
Centromere Position:	Acrocentric^[1] (12.0 Mbp^[2])
Chr:	21
Ensembl Id:	21
Entrez Id:	21
Ncbi Id:	21
Ucsc Id:	21
Refseq Id:	NC_000021
Genbank Id:	CM000683

Chromosome 21 is one of the 23 pairs of chromosomes in humans. Chromosome 21 is both the smallest human autosome and chromosome,^[3] with 46.7 million base pairs (the building material of DNA) representing about 1.5 percent of the total DNA in cells. Most people have two copies of chromosome 21, while those with three copies of chromosome 21 (trisomy 21) have Down syndrome.

Researchers working on the Human Genome Project announced in May 2000 that they had determined the sequence of base pairs that make up this chromosome.^[4] Chromosome 21 was the second human chromosome to be fully sequenced, after chromosome 22.

Genes

Number of genes

The following are some of the gene count estimates of human chromosome 21. Because researchers use different approaches to genome annotation, their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction). Among various projects, the collaborative consensus coding sequence project (CCDS) takes an extremely conservative strategy. Thus CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes.^[5]

Estimated by	Protein-coding genes	Non-coding RNA genes	Pseudogenes	Source	Release date
	212	—	—	^[6]	2022-10-26
HGNC	215	185	194	^[7]	2022-12-23
	221	447	185	^[8]	2023-07-17
	252	—	—	^[9]	2018-02-28
	256	356	207	^[10] ^[11] ^[12]	2017-05-19

Gene list

The following is a partial list of genes on human chromosome 21. For complete list, see the link in the infobox at the top of the article.

In addition, the chromosome has many genes for keratin-associated protein, with symbols: KRTAP6-1, KRTAP6-2, KRTAP6-3, KRTAP7-1, KRTAP8-1, KRTAP10-1, KRTAP10-2, KRTAP10-3, KRTAP10-4, KRTAP10-5, KRTAP10-6, KRTAP10-7, KRTAP10-8, KRTAP10-9, KRTAP10-10, KRTAP10-11, KRTAP10-12, KRTAP11-1, KRTAP12-1, KRTAP12-1, KRTAP12-2, KRTAP12-3, KRTAP12-4, KRTAP13-1, KRTAP13-2, KRTAP13-3, KRTAP13-4, KRTAP15-1, KRTAP19-1, KRTAP19-2, KRTAP19-3, KRTAP19-4, KRTAP19-5, KRTAP19-6, KRTAP19-7, KRTAP19-8, KRTAP20-1, KRTAP20-2, KRTAP20-3, KRTAP20-4, KRTAP21-1, KRTAP21-2, KRTAP21-3, KRTAP22-1, KRTAP22-2, KRTAP23-1, KRTAP24-1, KRTAP25-1, KRTAP26-1, KRTAP27-1.

Diseases and disorders

The following diseases and disorders are some of those related to genes on chromosome 21:

• Acute myeloid leukemia
• Alzheimer's disease
• Amyotrophic lateral sclerosis
• Atrial fibrillation, familial
• Autoimmune polyendocrine syndrome type 1
• Basal ganglia calcification
• Bartsocas–Papas syndrome
• Bethlem myopathy
• Closed angle glaucoma
• Cataract
• CHAND syndrome
• Down syndrome
• Epilepsy
• Erondu–Cymet syndrome
• Ewing sarcoma
• Galloway Mowat syndrome
• Glucocorticoid deficiency
• Hepatitis B (susceptibility to)
• Hereditary motor and sensory neuropathy
• Holocarboxylase synthetase deficiency
• Homocystinuria
• Hyperhomocysteinemia
• Hypotrichosis
• Immunodeficiency
• Inflammatory bowel disease
• Intellectual developmental disorder
• Jervell and Lange-Nielsen syndrome
• Keppen–Lubinsky syndrome
• Knobloch syndrome
• Leukocyte adhesion deficiency-1
• Majewski osteodysplastic primordial dwarfism type II (MOPD II, or MOPD2)
• Non-small cell lung carcinoma^[13]
• Neurodevelopmental disorder
• Nonsyndromic deafness
• Parkinson disease
• Peripheral neuropathy
• Phosphofructokinase deficiency
• Primary ciliary dyskinesia
• Primary immunodeficiency
• Primitive neuroectodermal tumor
• Prostate cancer
• Romano–Ward syndrome
• Spastic quadriplegia
• Ullrich congenital muscular dystrophy
• Unverricht–Lundborg disease, a form of progressive myoclonus epilepsy
• ZTTK syndrome

Chromosomal conditions

The following conditions are caused by changes in the structure or number of copies of chromosome 21:

• Cancers: Rearrangements (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. Another form of leukemia, acute myeloid leukemia, has been associated with a translocation between chromosomes 8 and 21.
• In a small percentage of cases, Down syndrome is caused by a rearrangement of chromosomal material between chromosome 21 and another chromosome. As a result, a person has the usual two copies of chromosome 21, plus extra material from chromosome 21 attached to another chromosome. These cases are called translocation Down syndrome. Researchers believe that extra copies of genes on chromosome 21 disrupt the course of normal development, causing the characteristic features of Down syndrome and the increased risk of medical problems associated with this disorder.
• Other changes in the number or structure of chromosome 21 can have a variety of effects, including intellectual disability, delayed development, and characteristic facial features. In some cases, the signs and symptoms are similar to those of Down syndrome. Changes to chromosome 21 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 both ends of a broken chromosome are reunited.
• Duplication in amyloid precursor protein (APP) locus (duplicated segment varies in length but includes APP) on Chromosome 21 was found to cause early onset familial Alzheimer's disease in a French family set and a Dutch family set. Compared to Alzheimer's caused by missense mutations in APP, the frequency of the Alzheimer's caused by APP duplications is significant. All patients that have an extra copy of APP gene due to the locus duplication show Alzheimer's with severe cerebral amyloid angiopathy.

Cytogenetic band

G-bands of human chromosome 21 in resolution 850 bphs! Chr.! Arm^[14] ! Band^[15] ! ISCN
start^[16] ! ISCN
stop! Basepair
start! Basepair
stop! Stain^[17] ! Density

21	p	13	0	311			gvar
21	p	12	311	683			stalk
21	p	11.2	683	1056			gvar
21	p	11.1	1056	1274			acen
21	q	11.1	1274	1367			acen
21	q	11.2	1367	1584			gneg
21	q	21.1	1584	2019			gpos	100
21	q	21.2	2019	2144			gneg
21	q	21.3	2144	2330			gpos	75
21	q	22.11	2330	2485			gneg
21	q	22.12	2485	2610			gpos	50
21	q	22.13	2610	2703			gneg
21	q	22.2	2703	2858			gpos	50
21	q	22.3	2858	3200			gneg

References

• Antonarakis SE, Lyle R, Dermitzakis ET, Reymond A, Deutsch S . Chromosome 21 and down syndrome: from genomics to pathophysiology . Nat Rev Genet . 2004 . 725–38 . 5 . 10 . 15510164 . 10.1038/nrg1448. 5487794 .
• Antonarakis SE, Lyle R, Deutsch S, Reymond A . Chromosome 21: a small land of fascinating disorders with unknown pathophysiology . Int J Dev Biol . 2002 . 89–96 . 46 . 1 . 11902692.
• Antonarakis SE . Chromosome 21: from sequence to applications . Curr Opin Genet Dev . 2001 . 241–6 . 11 . 3 . 11377958 . 10.1016/S0959-437X(00)00185-4.
• Gilbert F . Disease genes and chromosomes: disease maps of the human genome. Chromosome 21 . Genet Test . 1997 . 301–6 . 1 . 4 . 10464663 . 10.1089/gte.1997.1.301.
• Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML . The DNA sequence of human chromosome 21 . Nature . 2000 . 311–9 . 405 . 6784 . 10830953 . 10.1038/35012518. 2000Natur.405..311H . free .
• Sawinska M, Ladon D . Mechanism, detection and clinical significance of the reciprocal translocation t(12;21)(p12;q22) in the children suffering from acute lymphoblastic leukaemia . Leuk Res . 2004 . 35–42 . 28 . 1 . 14630078 . 10.1016/S0145-2126(03)00160-7.
• Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T, Campion D . APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy . Nature Genetics . 2005 . 24–6. 38. 1. 16369530 . 10.1038/ng1718. 559054 .
• Rauch . Anita . Thiel . Christian T. . Schindler . Detlev . Wick . Ursula . Crow . Yanick J. . Ekici . Arif B. . van Essen . Anthonie J. . Goecke . Timm O. . Al-Gazali . Lihadh . Lihadh Al-Gazali . Chrzanowska . Krystyna H. . Zweier . Christiane . Brunner . Han G. . Becker . Kristin . Curry . Cynthia J. . Cynthia J. Curry . Dallapiccola . Bruno . Koenraad Devriendt . Arnd Dörfler . Esther Kinning . André Megarbane . Peter Meinecke . Robert K. Semple . Stephanie Spranger . Annick Toutain . Richard C. Trembath . Egbert Voss . Louise Wilson . Raoul Hennekam . Francis de Zegher . Helmut-Günther Dörr . André Reis . Mutations in the Pericentrin (PCNT) Gene Cause Primordial Dwarfism . Science Online . 2008 . 816–9 . 319 . 5864 . 10.1126/science.1151174 . 18174396 . 2008Sci...319..816R . 23055733 . free.

External links

• Web site: National Institutes of Health . Chromosome 21 . Genetics Home Reference . 2017-05-06 . 2011-06-05 . https://web.archive.org/web/20110605075438/http://ghr.nlm.nih.gov/chromosome=21 . dead .
• Web site: Chromosome 21. Human Genome Project Information Archive 1990–2003. 2017-05-06.

Notes and References

1. Book: Tom Strachan. Andrew Read. Human Molecular Genetics. 2 April 2010. Garland Science. 978-1-136-84407-2. 45.
2. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). Last update 2014-06-03. Retrieved 2017-04-26.
3. Web site: Chromosome 21.
4. 10.1038/35012518. 10830953. The DNA sequence of human chromosome 21. Nature. 405. 6784. 311–319. 2000. Hattori. M.. Fujiyama. A.. Taylor. T. D.. Watanabe. H.. Yada. T.. Park. H.-S.. Toyoda. A.. Ishii. K.. Totoki. Y.. Choi. D.-K.. Soeda. E.. Ohki. M.. Takagi. T.. Sakaki. Y.. Taudien. S.. Blechschmidt. K.. Polley. A.. Menzel. U.. Delabar. J.. Kumpf. K.. Lehmann. R.. Patterson. D.. Reichwald. K.. Rump. A.. Schillhabel. M.. Schudy. A.. Zimmermann. W.. Rosenthal. A.. Kudoh. J.. Shibuya. K.. 2000Natur.405..311H. 29. free.
5. Pertea M, Salzberg SL. Between a chicken and a grape: estimating the number of human genes. . Genome Biol . 2010 . 11 . 5 . 206 . 20441615 . 10.1186/gb-2010-11-5-206 . 2898077 . free .
6. Web site: Search results - 21[CHR] AND "Homo sapiens"[Organism] AND ("has ccds"[Properties] AND alive[prop]) - Gene . NCBI . CCDS Release 24 for Homo sapiens . 2022-10-26 . 2022-12-23.
7. Web site: Statistics & Downloads for chromosome 21 . HUGO Gene Nomenclature Committee . 2022-12-23 . 2022-12-23 . 2017-06-29 . https://web.archive.org/web/20170629095146/http://www.genenames.org/cgi-bin/statistics?c=21 . dead .
8. Web site: Chromosome 21: Chromosome summary - Homo sapiens . Ensembl Release 110 . 2023-07-17 . 2024-02-17.
9. Web site: Human chromosome 21: entries, gene names and cross-references to MIM . UniProt . 2018-02-28 . 2018-03-16.
10. Web site: Search results - 21[CHR] AND "Homo sapiens"[Organism] AND ("genetype protein coding"[Properties] AND alive[prop]) - Gene . NCBI . 2017-05-19 . 2017-05-20.
11. Web site: Search results - 21[CHR] AND "Homo sapiens"[Organism] AND (("genetype miscrna"[Properties] OR "genetype ncrna"[Properties] OR "genetype rrna"[Properties] OR "genetype trna"[Properties] OR "genetype scrna"[Properties] OR "genetype snrna"[Properties] OR "genetype snorna"[Properties]) NOT "genetype protein coding"[Properties] AND alive[prop]) - Gene . NCBI . 2017-05-19 . 2017-05-20.
12. Web site: Search results - 21[CHR] AND "Homo sapiens"[Organism] AND ("genetype pseudo"[Properties] AND alive[prop]) - Gene . NCBI . 2017-05-19 . 2017-05-20.
13. Kohno . T. . Kawanishi . M. . Matsuda . S. . Ichikawa . H. . Takada . M. . Ohki . M. . Yamamoto . T. . Yokota . J. . March 1998 . Homozygous deletion and frequent allelic loss of the 21q11.1-q21.1 region including the ANA gene in human lung carcinoma . Genes, Chromosomes & Cancer . 21 . 3 . 236–243 . 10.1002/(sici)1098-2264(199803)21:3<236::aid-gcc8>3.0.co;2-0 . 1045-2257 . 9523199. 24082301 .
14. "p": Short arm; "q": Long arm.
15. For cytogenetic banding nomenclature, see article locus.
16. These values (ISCN start/stop) are based on the length of bands/ideograms from the ISCN book, An International System for Human Cytogenetic Nomenclature (2013). Arbitrary unit.
17. gpos: Region which is positively stained by G banding, generally AT-rich and gene poor; gneg: Region which is negatively stained by G banding, generally CG-rich and gene rich; acen Centromere. var: Variable region; stalk: Stalk.