Chromosome 21 (human)

Chromosome 21 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. The trisomy of the 21st chromosome causes Down Syndrome. Chromosome 21 is the smallest human chromosome, with 48 million nucleotides (the building material of DNA) representing about 1.5 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, after chromosome 22.

Identifying genes on each chromosome is an active area of genetic research. However, because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Depending on the genome annotation used, chromosome 21 contains 477 or 635 genes.^[2][3]

Genes

The following are some of the genes located on chromosome 21:

• APP: amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)^[4]
• C21orf59: Chromosome 21 open reading frame 59
• CBS: cystathionine-beta-synthase
• CLDN14: claudin 14
• HLCS: holocarboxylase synthetase (biotin-(proprionyl-Coenzyme A-carboxylase (ATP-hydrolysing)) ligase)
• KCNE1: potassium voltage-gated channel, Isk-related family, member 1
• KCNE2: potassium voltage-gated channel, Isk-related family, member 2
• LAD: leukocyte adhesion deficiency (symbols are ITGB2, CD18, LCAMB)
• SOD1: superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))
• TMPRSS3: transmembrane protease, serine 3
• PCNT: centrosomal pericentrin
• DSCR1: Down Syndrome critical region 1^[5]
• DYRK1A: dual specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
• RRP1B: ribosomal RNA processing 1 homolog B
• S100B: calcium binding protein

Diseases & disorders

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

• Alzheimer's disease^[4]
  • Alzheimer's disease type 1
• Amyotrophic lateral sclerosis
  • Amyotrophic lateral sclerosis type 1
• Autoimmune polyendocrine syndrome
  • Autoimmune polyendocrine syndrome type 1
• Down syndrome
• Erondu–Cymet syndrome
• Holocarboxylase synthetase deficiency
• Homocystinuria
• Jervell and Lange-Nielsen syndrome
• Leukocyte adhesion deficiency
• Majewski osteodysplastic primordial dwarfism type II (MOPD II, or MOPD2)
• Nonsyndromic deafness
  • Nonsyndromic deafness, autosomal recessive
• Romano-Ward 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 mental retardation, 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 (Rovelet-Lecrux et al.) and a Dutch family set.^[4] 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.

References

• Antonarakis SE, Lyle R, Dermitzakis ET, Reymond A, Deutsch S (2004). "Chromosome 21 and down syndrome: from genomics to pathophysiology". Nat Rev Genet 5 (10): 725–38. doi:10.1038/nrg1448. PMID 15510164. 
• Antonarakis SE, Lyle R, Deutsch S, Reymond A (2002). "Chromosome 21: a small land of fascinating disorders with unknown pathophysiology". Int J Dev Biol 46 (1): 89–96. PMID 11902692. 
• Antonarakis SE (2001). "Chromosome 21: from sequence to applications". Curr Opin Genet Dev 11 (3): 241–6. doi:10.1016/S0959-437X(00)00185-4. PMID 11377958. 
• Gilbert F (1997). "Disease genes and chromosomes: disease maps of the human genome. Chromosome 21". Genet Test 1 (4): 301–6. doi:10.1089/gte.1997.1.301. PMID 10464663. 
• 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 (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953. 
• Sawinska M, Ladon D (2004). "Mechanism, detection and clinical significance of the reciprocal translocation t(12;21)(p12;q22) in the children suffering from acute lymphoblastic leukaemia". Leuk Res 28 (1): 35–42. doi:10.1016/S0145-2126(03)00160-7. PMID 14630078. 
• 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. (2005). "APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy". Nature Genetics 38 (1): 24–6. doi:10.1038/ng1718. PMID 16369530. 
• Anita Rauch, Christian T. Thiel, Detlev Schindler, Ursula Wick, Yanick J. Crow, Arif B. Ekici, Anthonie J. van Essen, Timm O. Goecke, Lihadh Al-Gazali, Krystyna H. Chrzanowska, Christiane Zweier, Han G. Brunner, Kristin Becker, Cynthia J. Curry, Bruno Dallapiccola, 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 (2008). "Mutations in the Pericentrin (PCNT) Gene Cause Primordial Dwarfism". Science Online: 7.