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Genetics Home Reference: your guide to understanding genetic conditions
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Chromosome 12

Reviewed February 2013

What is chromosome 12?

Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 12, one copy inherited from each parent, form one of the pairs. Chromosome 12 spans almost 134 million DNA building blocks (base pairs) and represents between 4 and 4.5 percent of the total DNA in cells.

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 12 likely contains 1,100 to 1,200 genes that provide instructions for making proteins. These proteins perform a variety of different roles in the body.

Genes on chromosome 12 are among the estimated 20,000 to 25,000 total genes in the human genome.

Genetics Home Reference includes these genes on chromosome 12:

  • AAAS
  • ABCC9
  • ACADS
  • ACVRL1
  • ALX1
  • AMHR2
  • AQP2
  • ATN1
  • ATP2A2
  • ATP6V0A2
  • ATXN2
  • BBS10
  • CACNA1C
  • CDKN1B
  • CEP290
  • COL2A1
  • CYP27B1
  • DCN
  • DDX11
  • DHH
  • EIF2B1
  • ETV6
  • FGD4
  • FGF23
  • GDF3
  • GNPTAB
  • GNS
  • GRIP1
  • GYS2
  • HAL
  • HPD
  • HSPB8
  • IRAK4
  • ISCU
  • KCNA1
  • KIF21A
  • KMT2D
  • KRAS
  • KRT1
  • KRT3
  • KRT4
  • KRT5
  • KRT6A
  • KRT6B
  • KRT6C
  • KRT81
  • KRT83
  • KRT86
  • LDHB
  • LEMD3
  • LRRK2
  • MMAB
  • MVK
  • MYBPC1
  • MYO1A
  • PAH
  • PFKM
  • PKP2
  • POLR3B
  • PPP1R12A
  • PRICKLE1
  • PRPH
  • PTPN11
  • RPS26
  • SCNN1A
  • SLC11A2
  • SLCO1B1
  • SLCO1B3
  • TBX5
  • TNFRSF1A
  • TPI1
  • TRPV4
  • TUBA1A
  • VDR
  • VWF
  • WNK1

How are changes in chromosome 12 related to health conditions?

Many genetic conditions are related to changes in particular genes on chromosome 12. This list of disorders associated with genes on chromosome 12 provides links to additional information.

Genetics Home Reference includes these conditions related to genes on chromosome 12:

  • achondrogenesis
  • amyotrophic lateral sclerosis
  • arrhythmogenic right ventricular cardiomyopathy
  • autoimmune Addison disease
  • autoimmune lymphoproliferative syndrome
  • Bardet-Biedl syndrome
  • Buschke-Ollendorff syndrome
  • Cantú syndrome
  • cardiofaciocutaneous syndrome
  • Charcot-Marie-Tooth disease
  • coloboma
  • congenital fibrosis of the extraocular muscles
  • congenital stromal corneal dystrophy
  • core binding factor acute myeloid leukemia
  • cutis laxa
  • Czech dysplasia
  • Darier disease
  • dentatorubral-pallidoluysian atrophy
  • Diamond-Blackfan anemia
  • distal arthrogryposis type 1
  • distal hereditary motor neuropathy, type II
  • Dowling-Degos disease
  • epidermolysis bullosa simplex
  • epidermolytic hyperkeratosis
  • episodic ataxia
  • familial dilated cardiomyopathy
  • focal palmoplantar keratoderma
  • Fraser syndrome
  • frontonasal dysplasia
  • glycogen storage disease type 0
  • glycogen storage disease type VII
  • hereditary hemorrhagic telangiectasia
  • hereditary hypophosphatemic rickets
  • hereditary sensory and autonomic neuropathy type II
  • histidinemia
  • Holt-Oram syndrome
  • hyperphosphatemic familial tumoral calcinosis
  • hypochondrogenesis
  • hypochromic microcytic anemia with iron overload
  • IRAK-4 deficiency
  • isolated lissencephaly sequence
  • Joubert syndrome
  • Kabuki syndrome
  • Klippel-Feil syndrome
  • Kniest dysplasia
  • lactate dehydrogenase deficiency
  • Leber congenital amaurosis
  • Legg-Calvé-Perthes disease
  • leukoencephalopathy with vanishing white matter
  • lissencephaly with cerebellar hypoplasia
  • Meckel syndrome
  • Meesmann corneal dystrophy
  • metatropic dysplasia
  • methylmalonic acidemia
  • mevalonate kinase deficiency
  • microphthalmia
  • monilethrix
  • mucolipidosis II alpha/beta
  • mucolipidosis III alpha/beta
  • mucopolysaccharidosis type III
  • multiple endocrine neoplasia
  • multiple lentigines syndrome
  • multiple sclerosis
  • myopathy with deficiency of iron-sulfur cluster assembly enzyme
  • nephrogenic diabetes insipidus
  • nonsyndromic deafness
  • Noonan syndrome
  • pachyonychia congenita
  • Parkinson disease
  • PDGFRB-associated chronic eosinophilic leukemia
  • persistent Müllerian duct syndrome
  • phenylketonuria
  • platyspondylic lethal skeletal dysplasia, Torrance type
  • Pol III-related leukodystrophy
  • PRICKLE1-related progressive myoclonus epilepsy with ataxia
  • pseudohypoaldosteronism type 1
  • pseudohypoaldosteronism type 2
  • Rotor syndrome
  • Senior-Løken syndrome
  • short-chain acyl-CoA dehydrogenase deficiency
  • spinocerebellar ataxia type 2
  • spondyloepimetaphyseal dysplasia, Strudwick type
  • spondyloepiphyseal dysplasia congenita
  • spondyloperipheral dysplasia
  • Stickler syndrome
  • Swyer syndrome
  • Timothy syndrome
  • triosephosphate isomerase deficiency
  • triple A syndrome
  • tumor necrosis factor receptor-associated periodic syndrome
  • tyrosinemia
  • vitamin D-dependent rickets
  • von Willebrand disease
  • Warsaw breakage syndrome
  • white sponge nevus

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 12.

cancers

Changes in chromosome 12 have been identified in several types of cancer. These genetic changes are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. For example, rearrangements (translocations) of genetic material between chromosome 12 and other chromosomes are often found in certain cancers of blood-forming cells (leukemias) and cancers of immune system cells (lymphomas). Additionally, somatic mutations may lead to an extra copy of chromosome 12 (trisomy 12) in cancer cells, specifically a type of leukemia called chronic lymphocytic leukemia.

Translocations involving chromosome 12 have also been found in solid tumors such as lipomas and liposarcomas, which are made up of fatty tissue. In these tumors, the most common chromosome 12 rearrangements involve the long (q) arm in a region designated q13-q15. Abnormalities of chromosome 12 have been identified in at least two other rare tumors, angiomatoid fibrous histiocytomas and clear cell sarcomas. Angiomatoid fibrous histiocytomas occur primarily in adolescents and young adults and are usually found in the arms and legs (extremities). Clear cell sarcomas occur most often in young adults and tend to be associated with tendons and related structures called aponeuroses.

Researchers are working to determine which genes on chromosome 12 are disrupted by translocations, and they are studying how these chromosomal changes could contribute to the uncontrolled growth and division of tumor cells.

Pallister-Killian mosaic syndrome

Pallister-Killian mosaic syndrome is usually caused by the presence of an abnormal extra chromosome called an isochromosome 12p or i(12p). An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms. Isochromosome 12p is a version of chromosome 12 made up of two p arms.

Cells normally have two copies of each chromosome, one inherited from each parent. In people with Pallister-Killian mosaic syndrome, cells have the two usual copies of chromosome 12, but some cells also have the isochromosome 12p. These cells have a total of four copies of all the genes on the p arm of chromosome 12. The extra genetic material from the isochromosome disrupts the normal course of development, causing the characteristic features of this disorder.

Although Pallister-Killian mosaic syndrome is usually caused by an isochromosome 12p, other, more complex chromosomal changes involving chromosome 12 are responsible for the disorder in rare cases.

PDGFRB-associated chronic eosinophilic leukemia

Translocations involving chromosome 12 are involved in a type of blood cell cancer called PDGFRB-associated chronic eosinophilic leukemia. This condition is characterized by an increased number of eosinophils, a type of white blood cell. The most common translocation that causes this condition fuses part of the PDGFRB gene from chromosome 5 with part of the ETV6 gene from chromosome 12, written as t(5;12)(q31-33;p13). Translocations that fuse the PDGFRB gene with other genes can also cause PDGFRB-associated chronic eosinophilic leukemia, but these translocations are relatively uncommon. These translocations are acquired during a person's lifetime and are present only in cancer cells. This type of genetic change, called a somatic mutation, is not inherited.

The protein produced from the ETV6-PDGFRB fusion gene, called ETV6/PDGFRβ, functions differently than the proteins normally produced from the individual genes. The ETV6 protein normally turns off (represses) gene activity and the PDGFRβ protein plays a role in turning on (activating) signaling pathways. The ETV6/PDGFRβ protein is always turned on, activating signaling pathways and gene activity. When the ETV6-PDGFRB fusion gene mutation occurs in cells that develop into blood cells, the growth of eosinophils (and occasionally other white blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRB-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.

other chromosomal conditions

Other changes in the number or structure of chromosome 12 can have a variety of effects on health and development. These effects include intellectual disability, slow growth, distinctive facial features, weak muscle tone (hypotonia), skeletal abnormalities, and heart defects.

Several different changes involving chromosome 12 have been reported, including an extra piece of the chromosome in each cell (partial trisomy 12), a missing segment of the chromosome in each cell (partial monosomy 12), and a circular structure called a ring chromosome 12. Ring chromosomes occur 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 12?

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 12
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about chromosome 12?

You may find the following resources about chromosome 12 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 12?

cancer ; cell ; chromosome ; chronic ; disability ; DNA ; eosinophils ; fatty tissue ; fusion gene ; gene ; hypotonia ; immune system ; inherited ; isochromosome ; leukemia ; mast cells ; monosomy ; mosaic ; muscle tone ; mutation ; neutrophils ; protein ; ring chromosomes ; somatic mutation ; syndrome ; tissue ; translocation ; trisomy ; tumor ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

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  • Dufke A, Walczak C, Liehr T, Starke H, Trifonov V, Rubtsov N, Schöning M, Enders H, Eggermann T. Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker. Eur J Hum Genet. 2001 Aug;9(8):572-6. (http://www.ncbi.nlm.nih.gov/pubmed/11528501?dopt=Abstract)
  • Ensembl Human Map View: Chromosome 12 (http://www.ensembl.org/Homo_sapiens/Location/Chromosome?chr=12;r=12:1-133275309)
  • Gilbert F, Kauff N. Disease genes and chromosomes: disease maps of the human genome.Chromosome 12. Genet Test. 2000;4(3):319-33. (http://www.ncbi.nlm.nih.gov/pubmed/11142767?dopt=Abstract)
  • Haferlach C, Bacher U, Schnittger S, Alpermann T, Zenger M, Kern W, Haferlach T. ETV6 rearrangements are recurrent in myeloid malignancies and are frequently associated with other genetic events. Genes Chromosomes Cancer. 2012 Apr;51(4):328-37. doi: 10.1002/gcc.21918. Epub 2011 Dec 8. (http://www.ncbi.nlm.nih.gov/pubmed/22162288?dopt=Abstract)
  • Italiano A, Cardot N, Dupré F, Monticelli I, Keslair F, Piche M, Mainguené C, Coindre JM, Pedeutour F. Gains and complex rearrangements of the 12q13-15 chromosomal region in ordinary lipomas: the "missing link" between lipomas and liposarcomas? Int J Cancer. 2007 Jul 15;121(2):308-15. (http://www.ncbi.nlm.nih.gov/pubmed/17372913?dopt=Abstract)
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  • Map Viewer: Genes on Sequence (http://www.ncbi.nlm.nih.gov/mapview/maps.cgi?ORG=human&MAPS=ideogr,ugHs,genes&CHR=12)
  • Montgomery KT, Lee E, Miller A, Lau S, Shim C, Decker J, Chiu D, Emerling S, Sekhon M, Kim R, Lenz J, Han J, Ioshikhes I, Renault B, Marondel I, Yoon SJ, Song K, Murty VV, Scherer S, Yonescu R, Kirsch IR, Ried T, McPherson J, Gibbs R, Kucherlapati R. A high-resolution map of human chromosome 12. Nature. 2001 Feb 15;409(6822):945-6. (http://www.ncbi.nlm.nih.gov/pubmed/11237017?dopt=Abstract)
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  • Thway K. Angiomatoid fibrous histiocytoma: a review with recent genetic findings. Arch Pathol Lab Med. 2008 Feb;132(2):273-7. doi: 10.1043/1543-2165(2008)132[273:AFHARW]2.0.CO;2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18251589?dopt=Abstract)
  • UCSC Genome Browser: Statistics (http://genome.cse.ucsc.edu/goldenPath/stats.html)
  • Yeung A, Francis D, Giouzeppos O, Amor DJ. Pallister-Killian syndrome caused by mosaicism for a supernumerary ring chromosome 12p. Am J Med Genet A. 2009 Mar;149A(3):505-9. doi: 10.1002/ajmg.a.32664. (http://www.ncbi.nlm.nih.gov/pubmed/19215037?dopt=Abstract)
  • Zhou MH, Gao L, Jing Y, Xu YY, Ding Y, Wang N, Wang W, Li MY, Han XP, Sun JZ, Wang LL, Yu L. Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia. Ann Hematol. 2012 Aug;91(8):1235-43. doi: 10.1007/s00277-012-1431-4. Epub 2012 Feb 29. (http://www.ncbi.nlm.nih.gov/pubmed/22373549?dopt=Abstract)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2013
Published: December 16, 2014