Chimera (genetics)
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2008-07-10T03:14:23Z
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[[Image:Sheep goat chimera.jpg|thumb|right|300px|An example of a sheep-goat chimera.]]
In [[zoology]], a '''chimera''' is an animal that has two or more different populations of genetically distinct [[cell (biology)|cells]] that originated in different [[zygote]]s; if the different cells emerged from the same zygote, it is called a [[mosaicism]]. Chimerism is rare in human beings: there have been only about 40 reported cases.
Chimeras are formed from four parent cells (two fertilized eggs or early embryos fuse together) or from three parent cells (a fertilized egg is fused with an unfertilized egg or a fertilized egg is fused with an extra sperm). Each population of cells keeps its own character and the resulting animal is a mixture of mis-matched parts. An analogy is two [[jigsaw puzzle]]s cut using an identical cutter, but with different pictures. A single puzzle can be made out of the mis-matched parts, but the completed puzzle will show parts of both pictures.
This condition is either inherited, or it is acquired through the infusion of allogeneic [[hematopoietic cell]]s during [[Organ transplant|transplantation]] or [[Blood transfusion|transfusion]]. In fraternal twins, chimerism occurs by means of blood-vessel [[anastomose]]s. The likelihood of a child being a chimera is increased if the child is created via [[in vitro fertilization]]. Chimeras can often breed, but the fertility and type of offspring depends on which cell line gave rise to the ovaries or testes.
==Tetragametic chimerism==
''Tetragametic chimerism'' is a less common cause of congenital chimerism. It occurs through the fertilization of two ova by two sperm, followed by the fusion of the zygotes and the development of an organism with intermingled cell lines. This happens at a very early stage of development, such as that of the [[mammalian embryogenesis|blastocyst]]. Such an organism is called a tetragametic chimera as it is formed from four [[gamete]]s — two [[ovum|eggs]] and two [[spermatozoon|sperm]]. Put another way, the chimera is formed from the merger of two [[fraternal twins]] in a very early (zygote or blastocyst) phase. As such, they can be male, female, or [[hermaphroditic]].
As the organism develops, the resulting chimera can come to possess [[organ (anatomy)|organ]]s that have different sets of [[chromosome]]s. For example, the chimera may have a [[liver]] composed of cells with one set of chromosomes and have a [[kidney]] composed of cells with a second set of chromosomes. This has occurred in [[human]]s, and at one time was thought to be extremely rare, though more recent evidence suggests that it is not as rare as previously believed. Most will go through life without realizing they are chimeras. The difference in phenotypes may be minute, or completely undetectable (''e.g.,'' having a [[Thumb#Hitchhiker's thumb|hitchhiker's thumb]] and a straight thumb, eyes of slightly different colors, differential hair growth on opposite sides of the body, etc). Another telltale of a person being a chimera is visible [[Blaschko's lines]].
Affected persons are identified by the finding of two populations of red cells or, if the zygotes are of opposite sex, [[ambiguous genitalia]] and [[hermaphroditism]] alone or in combination; such persons sometimes also have patchy [[skin]], [[hair]], or [[eye pigmentation]] ([[heterochromia]]). If the [[blastocyst]]s are of the same sex, it can only be detected through [[DNA testing]], although this is a rare procedure. If the blastocysts are of opposite sex, [[genitals]] of both sexes are often formed, either [[ovary]] and [[testis]], or combined [[ovotestes]], in one rare form of [[intersexuality]], a condition previously known as ''true [[hermaphroditism]]''. As of [[2003]], there were about 30-40 documented human cases in the literature, according to ''[[New Scientist]]''.[http://www.katewerk.com/chimera.html] Since hermaphroditic chimeras would be expected to be half of all chimeras, with purely male and purely female chimeras being one-quarter each, this would suggest that the condition is not particularly common.
Natural chimeras are almost never detected unless the offspring has abnormalities such as male/female or hermaphrodite characteristics or skin discolouring. The most noticeable are some male [[tortoiseshell cat]]s or animals with ambiguous sex organs. Recent studies of tortoiseshell male cats and unusually coloured tortoiseshell-like cats suggest that natural chimerism is far more common than previously realised and that it frequently goes undetected.{{Fact|date=September 2007}}
Chimerism can be detected in DNA testing. The [[Lydia Fairchild]] case, for example, was brought to court after DNA testing showed that her children could not be hers, since DNA did not match. The charge against her was dismissed when it became clear that Lydia was a chimera, with the matching DNA being found in her cervical tissue. Another case was that of Karen Keegan.<ref>"[http://www.five.tv/programmes/extraordinarypeople/twininside/ The Twin Inside Me: Extraordinary People]" Channel 5 TV, UK, 23:00 [[9 March]] [[2006]]</ref>
The tetragametic state has important implications for organ or [[Stem cell|stem-cell]] transplantation. Chimeras typically have [[immunologic tolerance]] to both cell lines. Thus, for a tetragametic human, a wider array of relatives and other persons may be eligible to be an [[organ donor]].{{Fact|date=February 2008}}
==Microchimerism==
''Microchimerism'' is the presence of a small number of cells, genetically distinct from those of the host individual. The most common form is [[fetomaternal microchimerism]] (or fetal chimerism) whereby cells from a [[fetus]] pass through into the mother. Fetal cells have been documented to persist in maternal circulation for as long as 38 years.<ref>{{cite journal|author= Evans PC, Lambert N, Maloney S, Furst DE, Moore JM, Nelson JL | title=Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma.| journal=Blood | year=1999 | pages=2033–2037 | volume=93 | issue=6}}</ref>
Microchimerism had also been shown to exist after [[blood transfusion]]s to a severely [[immunocompromised]] population of patients who suffered [[Physical trauma|trauma]].<ref>{{cite journal|author=Reed W, Lee TH, Norris PJ, Utter GH, Busch MP | title=Transfusion-associated microchimerism: a new complication of blood transfusions in severely injured patients | journal=Seminars in Hematology | year=2007 | pages=24–31 | volume=44 | issue=1 | doi= 10.1053/j.seminhematol.2006.09.012}} PMID 17198844 {{doi|10.1053/j.seminhematol.2006.09.012}}</ref><br /> Microchimerism has been implicated in autoimmune diseases. Two independent scientists (Carol M. Artlett and J. Lee Nelson) published data within a month of each other, suggesting that microchimeric cells of fetal origin may be involved in the pathogenesis of systemic sclerosis.<ref>{{cite journal|author= Evans PC, Lambert N, Maloney S, Furst DE, Moore JM, Nelson JL | title=Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma.| journal=Blood | year=1999 | pages=2033–2037 | volume=93 | issue=6}}</ref><ref>{{cite journal|author= Artlett CM, Smith JB, Jimenez SA | title=Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis.| journal=New England Journal of Medicine| year=1998 | pages=1186–1196 | volume=338 | issue=17|doi= 10.1056/NEJM199804233381704 | pmid=9554859}}</ref> Artlett went on to demonstrate that microchimeric cells of maternal origin may be involved in the pathogenesis of a group of autoimmune diseases found in children, juvenile idiopathic inflammatory myopathies (one example would be [[juvenile dermatomyositis]]).<ref>{{cite journal|author= Artlett CM, Ramos R, Jimenez SA, Patterson K, Miller FW, Rider LG | title=Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group.| journal=Lancet| year=2000 | pages=2155–2156 | volume=356 | issue=9248|doi= 10.1016/S0140-6736(00)03499-1}}</ref> Microchimerism has now been further implicated in other autoimmune diseases, including [[Lupus erythematosus|systemic lupus erythematosus]].<ref>{{cite journal|author= Johnson KL, McAlindon TE, Mulcahy E, Bianchi DW | title=Microchimerism in a female patient with systemic lupus erythematosus.| journal=Arthritis Rheum | year=2001 | pages=2107–2111 | volume=44 | issue=9|doi= 10.1002/1529-0131(200109)44:9<2107::AID-ART361>3.0.CO;2-9}}</ref> A recent alternative hypothesis of the role of microchimeric cells in lesions is that they may be facilitating tissue repair of the damaged organ.<ref>{{cite journal|author= Gilliam AC | title=Microchimerism and skin disease: true-true unrelated?| journal=J. Invest Dermatol | year=2006 | pages=239–241 | volume=126 | issue=2|doi= 10.1038/sj.jid.5700061}}</ref> However, although these foreign cells are found in the lesions of autoimmune diseases, their role in the cause of disease is yet to be fully uncovered. Microchimeric cells may be mediating damage, facilitating tissue repair, or alternatively, be innocent bystanders.
==Parasitic chimerism in anglerfishes==
Chimerism occurs naturally in adult [[Ceratiidae|Ceratioid]] [[anglerfish]]es and is in fact a natural and essential part of their lifecycle. One or more [[male]]s attach to a [[female]] as [[parasite]]s (they must do so, as they will never fully mature alone), eventually fusing into a single, [[hermaphrodite|hermaphroditic]] individual with a shared [[circulatory system]]. Once fused to a female, the males will reach sexual maturity, developing large [[testicle]]s as their other organs [[atrophy]].
==Germline chimerism==
{{Expand|date=April 2007}}
Germline chimerism is when the [[sperm]] and [[ovum|egg]] cells of an organism are not genetically identical to its own. It has recently been discovered that [[marmoset]]s can carry the reproductive cells of their twin siblings, because of placental fusion during development [http://www.pnas.org/cgi/content/abstract/0607426104v1][http://www.nytimes.com/2007/03/27/science/27marm.html] [http://www.newscientist.com/article/dn11464-marmosets-may-carry-their-siblings-sex-cells.html].
==Chimeras in research==
In biological research, chimeras are artificially produced by physically mixing cells from two different organisms. Chimeras are not [[Hybrid (biology)|hybrids]], which form from the fusion of [[gametes]] from two species (like a donkey and a horse) that form a single [[zygote]] that will develop as much as it can (in this case into a live [[mule]] if the parents are jackass and mare, or a [[hinny]] if the parents are stallion and jenney); in comparison, chimeras are the physical mixing of cells from two independent zygotes: for example, one from the donkey and one from the horse. "Chimera" is a broad term and is often applied to many different types of mixing of cells from two different species.
Some chimeras can result in the eventual development of an adult animal composed of cells from both donors, which may be of different [[species]] — for example, in [[1984]] a chimeric [[geep]] was produced by combining [[embryo]]s from a [[goat]] and a [[sheep]].<ref>{{cite news | url = http://jcgi.pathfinder.com/time/archive/preview/0,10987,921546,00.html | title = It's a Geep | publisher = [[Time (magazine)|Time]] | date = [[1984-02-27]] | accessdate = 2006-08-02 }}</ref> The "geep" has been a very important contributor to answering fundamental questions about development and the techniques used to create it may one day help save endangered species. For example, if one tried to let a goat embryo gestate in a sheep the sheep's immune system would reject the developing embryo and the goat would die; however, if one used a geep that shared markers of immunity with both sheep and goats, the goat embryo may survive. It may be possible to extend this practice for the purpose of preventing the extinction of some endangered animal species.
Such interspecies chimeras such as the "geep" are made in the laboratory and rarely with the purpose of generating living hybrid animals. In addition to the famous [[geep]], there are rat/mouse chimeras and a rabbit/human chimera which was destroyed within a few days for the purpose of harvesting stem cells. Intraspecies chimeras are created by transplanting embryonic cells from an animal with one trait into an embryo of an animal with a different trait. This practice is common in the field of [[embryology]] and has been a very important contributor to our current understanding of human and animal biology. For example, by mixing embryonic cells of differently coloured or otherwise genetically distinct mice (of the same species), researchers have been able to see how embryos form and which organs and tissues are related (arise from the similar cell lineages).
[[Hybridomas]] are not true chimeras as described above because they do not result from the mixture of two cell types but result from fusion of two species' cells into a single cell and artificial propagation of this cell in the laboratory. Hybridomas have been very important tools in biomedical research for decades.
In August 2003, researchers at the [[Shanghai Second Medical University]] in [[China]] reported that they had successfully fused human [[skin]] cells and dead [[rabbit]] eggs to create the first human chimeric embryos. The embryos were allowed to develop for several days in a laboratory setting, then destroyed to harvest the resulting [[stem cell]]s.[http://news.nationalgeographic.com/news/2005/01/0125_050125_chimeras.html] Because of the high therapeutic potential of human embryonic stem cells and the American moratorium on using discarded embryos from [[in vitro fertilization]] clinics as well as other concerns about using human embryos directly for research, scientists are trying to find ways to find alternative paths of research. However, increasingly realizable projects using part-human, part-animal chimeras as living factories not only for biopharmaceutical production but also for producing cells or organs (see [[hybridomas]]) for [[xenotransplantation]] raise a host of [[ethics|ethical]] and safety issues.
During November 2006, UK researchers from [[Newcastle University]] and [[King's College London]] applied to the [[Human Fertilisation and Embryology Authority]] for a three-year license to fuse human [[DNA]] with cow eggs. The proposal is to insert human DNA into a [[cow]]'s egg which has had its genetic material removed and then create an [[embryo]] by the same technique that produced [[Dolly the Sheep]]. The resulting embryo would be 99.9% human; the only bovine element would be DNA outside the nucleus of the cell.{{Fact|date=October 2007}} This research was attempted in the United States several years before and failed to yield such an embryo. In April 2008 the researchers from [[Newcastle University]] reported that their research had been successful. The resulting embryos lived for 3 days and the largest grew to a size of 32 cells. The researchers are aiming for embryos that live for 6 days so that embryonic stem cells can be harvested.
In 2007, scientists at the [[University of Nevada]] School of Medicine created a sheep that has 15% human cells and 85% animal cells. [http://www.presstv.ir/detail.aspx?id=3995§ionid=3510208]
Chimeras should not be confused with [[mosaic (genetics)|mosaics]], which are organisms with genetically different cell types, but which again originate from a single zygote.
==In popular culture==
*In the 2004 book ''[[Free Culture (book)|Free Culture]]'',<ref>{{cite book|last=Lessig|first=Lawrence|authorlink=Lawrence Lessig|title=[[Free Culture (book)|Free Culture]]|year=2004|chapter=Chapter 11: Chimera|url=http://www.free-culture.cc/freeculture.pdf }}</ref> author [[Lawrence Lessig]] digresses briefly to describe chimerism and suggest that it could, and had yet to, be well used as a [[television]] plot device (particularly for [[police procedural]]s involving [[genetic fingerprinting]]).
*The ''[[CSI: Crime Scene Investigation]]'' episode "[[Bloodlines (CSI episode)|Bloodlines]]" involves a man who is a chimera.
*In the ''[[House (TV series)|House]]'' episode "[[Cane and Able (House episode)|Cane and Able]]", a boy who believes he was abducted by aliens is diagnosed with chimerism.
*In an episode of ''[[The Office (US TV series)|The Office]]'', [[Dwight Schrute]] says that he resorbed his twin brother while in his mother's womb. He also says that he now has "the strength of a grown man and a little baby".
*A November 2006 episode of the [[American Broadcasting Company|ABC]] soap opera ''[[All My Children]]'' revealed that testing of Emma's DNA did not reveal a match with her mother, Annie, because Annie is a chimera.
*One of the subplots in [[Michael Crichton]]'s [[2006]] novel ''[[Next (novel)|Next]]'' deals with chimerism.
*In season three of the TV series ''[[Regenesis]]'', a girl accused of murder is found not guilty when DNA from her blood does not match the DNA found on the victim. She is later proven to be the killer when DNA from her saliva is shown to match that at the scene of the crime. The discrepancy between her blood and saliva is explained by her being a chimera.
*A [[Discovery Health Channel]] special called ''I Am My Own Twin'' focuses on chimeras with no outward characteristics of the trait.
*In the [[Playstation 3]] game [[Resistance: Fall of Man]], by [[Insomniac Games]], the monsters were referred to as Chimera due to their combination of human and alien DNA.
*A March 2008 [[Radio Lab]] episode explored the case of a human chimera.<ref>http://www.wnyc.org/shows/radiolab/episodes/2008/03/14</ref>
*In the ''[[30 Rock]]'' episode "[[MILF Island]]", the character [[Liz Lemon]] says that she used to have deformed baby foot which was thought to be the result of her eating her twin while her mother, Margaret Lemon, was pregnant.
*In the Stephen King novel "The Dark Half" Thad Beaumont the main character suffers from intense migraine headaches as a child. When on the operating table, his doctors find a human eye, ear and part of a nose growing inside Thad's skull, which was the cause of his headaches. The doctors explained this as Thad having absorbed his twin prior to birth.
==See also==
* [[Chimera (mythology)]]
* [[Chimera (plant)]]
* [[Mosaic (genetics)]]
* [[Chimaera (fish)]]
* [[Parahuman]]s
* [[Intersexual#Chimerism|Chimerism in human intersexuality]]
* [[Vanishing twin]]
* [[Lydia Fairchild]]
==References==
<references/>
<!--See [[Wikipedia:Footnotes]] for an explanation of how to generate footnotes using the <ref(erences/)> tags-->
* {{cite journal | author=Yu N, Kruskall MS, Yunis JJ, Knoll JH, Uhl L, Alosco S, Ohashi M, Clavijo O, Husain Z, Yunis EJ, Yunis JJ, Yunis EJ | title=Disputed maternity leading to identification of tetragametic chimerism | journal=N Engl J Med | year=2002 | pages=1545–52 | volume=346 | issue=20 | pmid=12015394 | doi=10.1056/NEJMoa013452}}
* Appel, Jacob M. "The Monster's Law", ''[[Genewatch]]'', Volume 19, Number 2, March-April 2007.
* Ainsworth, Claire ([[November 15]], [[2003]]). [http://www.newscientist.com/article.ns?id=mg18024215.100 ''The Stranger Within'']. ''[[New Scientist]]'' (subscription). (reprinted [http://www.katewerk.com/chimera.html here])
* Nelson, J. Lee (Scientific American, February 2008). [http://www.sciam.com/search/index.cfm?q=microchimerism Your Cells Are My Cells]
* Weiss, Rick ([[August 14]], [[2003]]). [http://pqasb.pqarchiver.com/washingtonpost/access/383989051.html?dids=383989051:383989051&FMT=ABS&FMTS=ABS:FT&fmac=&date=Aug+14%2C+2003&author=Rick+Weiss&desc=Cloning+Yields+Human-Rabbit+Hybrid+Embryo ''Cloning yields human-rabbit hybrid embryo'']. ''[[The Washington Post]]''.
* Weiss, Rick ([[February 13]], [[2005]]). [http://www.washingtonpost.com/wp-dyn/articles/A19781-2005Feb12.html ''U.S. Denies Patent for a too-human hybrid'']. ''[[The Washington Post]]''.
* Interesting Article with a very easy explanation of Chimera [http://www.damninteresting.com/?p=412]
* {{cite journal | author=L. M. Repas-Humpe, A. Humpe, R. Lynen, B. Glock, E. M. Dauber, G. Simson, W. R. Mayr, M. Köhler, S. Eber | title=A dispermic chimerism in a 2-year-old Caucasian boy | journal=Journal Annals of Hematology | year=1999| pages=431–434 | volume=78 | issue=9 | doi=10.1007/s002770050543}}
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