View source for Chimera (genetics)

{{Short description|Single organism composed of two or more different populations of genetically distinct cells}}
{{About|Chimera genetics|DNA sequencing artifacts|Chimera (molecular biology)}}
{{Distinguish|Chimera (mythology)}}
[[File:TwoColoredRoseChimera.jpg|thumb|upright|Two-colored rose chimera]]

A '''genetic chimerism''' or '''chimera''' ({{IPAc-en|k|aɪ|ˈ|m|ɪər|ə|,_|k|ɪ|-}} {{respell|ky|MEER|ə|,_|kih|-}}) is a single [[organism]] composed of [[cell (biology)|cells]] of different [[genotype]]s. [[Animal]] chimeras can be produced by the fusion of two (or more) [[embryo]]s. In plants and some animal chimeras, [[mosaic (genetics)|mosaicism]] involves
distinct types of [[tissue (biology)|tissue]] that originated from the same [[zygote]], but differ due to [[mutation]] during ordinary [[cell division]].

Normally, genetic chimerism is not visible on casual inspection; however, it has been detected in the course of proving parentage.<ref>{{cite news | last1=Friedman|first1=Lauren| title=The Stranger-Than-Fiction Story of a Woman Who Was Her Own Twin |url=https://businessinsider.com/lydia-fairchild-is-her-own-twin-2014-2 |work=[[Business Insider]] |date=2014-02-02 |access-date=2014-08-04}}</ref> More practically, in [[agronomy]], "chimera" indicates a plant or portion of a plant whose tissues are made up of two or more types of cells with different genetic makeup; it can derive from a bud mutation or, more rarely, at the grafting point, from the concrescence of cells of the two bionts; in this case it is commonly referred to as a "graft hybrid", although it is not a hybrid in the genetic sense of "hybrid".<ref>{{cite book |last1=Bou|first1=Jordi |last2=Virgós|first2=Ariadna|last3=Martínez-García |first3=Jaime |last4=Prat|first4=Salomé |title=Phytohormones in Plant Biotechnology and Agriculture |chapter=Potato Tuberization: Evidence for a SD-Dependent and a Gibberellin-Dependent Pathway of Induction |date=2003 |pages=57–66 |doi=10.1007/978-94-017-2664-1_6 |isbn=978-90-481-6472-1}}</ref>

In contrast, an individual where each cell contains genetic material from two organisms of different breeds, varieties, species or genera is called a [[Hybrid (biology)|hybrid]].<ref name="Taddeo Robert Hybrids and Chimeras">{{cite encyclopedia |last1=Taddeo |first1=Sarah |last2=Robert |first2=Jason S. |title='Hybrids and Chimeras: A Consultation on the Ethical and Social Implications of Creating Human/Animal Embryos in Research' (2007), by the HFEA |encyclopedia=Embryo Project Encyclopedia |date=4 November 2014 |hdl=10776/8232 |hdl-access=free }}</ref>

Another way that chimerism can occur in animals is by [[organ (biology)|organ]] transplantation, giving one individual tissues that developed from a different [[genome]]. For example, [[Organ transplantation|transplantation]] of [[bone marrow]] often determines the recipient's ensuing [[blood type]].<ref>{{cite journal |title=Temporal Change in Blood Group after Bone Marrow Transplant: A Case of Successful ABO-Incompatible Deceased Donor Transplant |journal=Case Rep Transplant |date=2020 |doi=10.1155/2020/7461052 |pmid=32774979 |pmc=7396079 |last1=Lam |first1=Susanna |last2=Hultin |first2=Sebastian |last3=Preston |first3=John |last4=Campbell |first4=Scott |volume=2020 |pages=1–4 |doi-access=free }}</ref>

==Classifications==

===Natural chimerism===
{{Needs expansion|date=October 2024}}
Some level of chimerism occurs naturally in the wild in many animal species, and in some cases may be a required (obligate) part of their life cycle. 

==== Sponges ====
Chimerism has been found in some species of marine sponges.<ref name="Blanquer,A" /> Four distinct genotypes have been found in a single individual, and there is potential for even greater genetic heterogeneity. Each genotype functions independently in terms of reproduction, but the different intra-organism genotypes behave as a single large individual in terms of ecological responses like growth.<ref name="Blanquer,A" />

==== In obligates ====
{{See also|Yellow crazy ant#Reproduction}}

It has been shown that male [[yellow crazy ant]]s are obligate chimeras, the first known such case. In this species, the queens have arisen from fertilized eggs with a genotype of RR (Reproductive × Reproductive), the sterile female workers show a RW arrangement (Reproductive × Worker), and the males instead of being haploid, as is usually the case for ants, also display a RW genotype, but for them the egg R and the sperm W do not fuse so they develop as a chimera with some cells carrying an R and others carrying a W genome.<ref>{{cite journal |last1=Darras |first1=H. |last2=Berney |first2=C. |last3=Hasin |first3=S. |last4=Drescher |first4=J. |last5=Feldhaar |first5=H. |last6=Keller |first6=L. |title=Obligate chimerism in male yellow crazy ants |journal=Science |date=7 April 2023 |volume=380 |issue=6640 |pages=55–58 |doi=10.1126/science.adf0419 |pmid=37023182 |bibcode=2023Sci...380...55D }}</ref><ref>{{cite journal |last1=Callaway |first1=Ewen |title=Crazy ants' strange genomes are a biological first |journal=Nature |date=6 April 2023 |doi=10.1038/d41586-023-01002-3 |pmid=37024590 }}</ref>

===Artificial chimerism ===
[[File:Backcrossing mice from chimera edit.svg|right|thumb|upright|Chimeric trait distribution by generation]]

Artificial chimerism refers to examples of chimerism that are produced by humans, either for research or commercial purposes. 

====Tetragametic chimerism====
[[File:African violet chimeras.jpg|right|thumb|upright=1|African violets exhibiting chimerism]]

Tetragametic chimerism is a form of congenital chimerism. This condition occurs through fertilizing two separate ova by two sperm, followed by aggregation of the two at the [[blastocyst]] or zygote stages. This results in the development of an organism with intermingled cell lines. Put another way, the chimera is formed from the merging of two [[twin|nonidentical twins]]. As such, they can be male, female, or intersex.<ref>{{cite journal |last1=Schoenle |first1=E. |last2=Schmid |first2=W. |last3=Schinzel |first3=A. |last4=Mahler |first4=M. |last5=Ritter |first5=M. |last6=Schenker |first6=T. |last7=Metaxas |first7=M. |last8=Froesch |first8=P. |last9=Froesch |first9=E. R. |title=46,XX/46,XY chimerism in a phenotypically normal man |journal=Human Genetics |date=July 1983 |volume=64 |issue=1 |pages=86–89 |doi=10.1007/BF00289485 |pmid=6575956 }}</ref><ref>{{cite journal |last1=Binkhorst |first1=M. |last2=de Leeuw |first2=N. |last3=Otten |first3=B.J. |title=A Healthy, Female Chimera with 46,XX/46,XY Karyotype |journal=Journal of Pediatric Endocrinology and Metabolism |date=January 2009 |volume=22 |issue=1 |pages=97–102 |doi=10.1515/jpem.2009.22.1.97 |pmid=19344081 }}</ref><ref>{{Cite journal |last1=Gencík |first1=A. |last2=Genciková |first2=A. |last3=Hrubisko |first3=M. |last4=Mergancová |first4=O. |date=1980 |title=Chimerism 46,XX/46,XY in a phenotypic female |journal=Human Genetics |volume=55 |issue=3 |pages=407–408 |doi=10.1007/bf00290226 |pmid=7203474 }}</ref><ref>{{Cite journal |last1=Farag |first1=T I |last2=Al-Awadi |first2=S A |last3=Tippett |first3=P |last4=el-Sayed |first4=M |last5=Sundareshan |first5=T S |last6=Al-Othman |first6=S A |last7=el-Badramany |first7=M H |date=December 1987 |title=Unilateral true hermaphrodite with 46,XX/46,XY dispermic chimerism |journal=Journal of Medical Genetics |volume=24 |issue=12 |pages=784–786 |pmc=1050410 |pmid=3430558 |doi=10.1136/jmg.24.12.784 }}</ref><ref>{{Cite journal |last1=Shah |first1=V. C. |last2=Krishna Murthy |first2=D. S. |last3=Roy |first3=S. |last4=Contractor |first4=P. M. |last5=Shah |first5=A. V. |date=November 1982 |title=True hermaphrodite: 46, XX/46, XY, clinical cytogenetic and histopathological studies |journal=Indian Journal of Pediatrics |volume=49 |issue=401 |pages=885–890 |doi=10.1007/bf02976984 |pmid=7182365 }}</ref><ref name="Strain" /><ref>{{Cite journal |last1=Hadjiathanasiou |first1=C. G. |last2=Brauner |first2=R. |last3=Lortat-Jacob |first3=S. |last4=Nivot |first4=S. |last5=Jaubert |first5=F. |last6=Fellous |first6=M. |last7=Nihoul-Fékété |first7=C. |last8=Rappaport |first8=R. |date=November 1994 |title=True hermaphroditism: genetic variants and clinical management |journal=The Journal of Pediatrics |volume=125 |issue=5 Pt 1 |pages=738–744 |doi=10.1016/s0022-3476(94)70067-2 |pmid=7965425 }}</ref>{{citation overkill|date=May 2022}}

The tetragametic state has important implications for organ or [[stem cell]] transplantation. Chimeras typically have [[immunologic tolerance]] to both cell lines.{{Citation needed|date=January 2017}}

====Microchimerism====
{{Main| Microchimerism}}

Microchimerism is the presence of a small number of cells that are genetically distinct from those of the host individual. Most people are born with a few cells genetically identical to their mothers' and the proportion of these cells goes down in healthy individuals as they get older. People who retain higher numbers of cells genetically identical to their mother's have been observed to have higher rates of some autoimmune diseases, presumably because the immune system is responsible for destroying these cells and a common immune defect prevents it from doing so and also causes autoimmune problems.

The higher rates of autoimmune diseases due to the presence of maternally derived cells is why in a 2010 study of a 40-year-old man with scleroderma-like disease (an autoimmune rheumatic disease), the female cells detected in his blood stream via FISH (fluorescence in situ hybridization) were thought to be maternally derived. However, his form of microchimerism was found to be due to a vanished twin, and it is unknown whether microchimerism from a vanished twin might predispose individuals to autoimmune diseases as well.<ref>{{cite journal |last1=Bellefon |first1=L. |last2=Heiman |first2=P. |last3=Kanaan |first3=S. |last4=Azzouz |first4=D. |last5=Rak |first5=J. |last6=Martin |first6=M. |last7=Roudier |first7=J. |last8=Roufosse |first8=F. |last9=Lambert |first9=C. |year=2010 |title=Cells from a vanished twin as a source of microchimerism 40 years later |journal=Chimerism |volume=1 |issue=2 |pages=56–60 |doi=10.4161/chim.1.2.14294 |pmid=21327048 |pmc=3023624}}</ref> Mothers often also have a few cells genetically identical to those of their children, and some people also have some cells genetically identical to those of their siblings (maternal siblings only, since these cells are passed to them because their mother retained them).{{Citation needed|date=January 2017}}

====Germline chimerism====
Germline chimerism occurs when the germ cells (for example, [[sperm]] and [[ovum|egg]] cells) of an organism are not genetically identical to its own. It has been recently discovered that [[marmoset]]s can carry the reproductive cells of their (fraternal) twin siblings due to placental fusion during development. (Marmosets almost always give birth to fraternal twins.)<ref name="Ross2007" /><ref>{{cite news | url=https://www.nytimes.com/2007/03/27/science/27marm.html | work=The New York Times | title=In the Marmoset Family, Things Really Do Appear to Be All Relative | first=Carl | last=Zimmer | date=2007-03-27 | access-date=2010-04-01}}</ref><ref>{{cite news | url=https://www.newscientist.com/article/dn11464-marmosets-may-carry-their-siblings-sex-cells.html| title=Marmosets may carry their sibling's sex cells| last=Hooper| first=Rowan| date=26 March 2007| work=[[New Scientist]]}}</ref>

==Types==

===Animals===

As the organism develops, it 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 humans, and at one time was thought to be extremely rare although more recent evidence suggests that this is not the case.<ref name="Norton" /><ref>{{cite book |last1=Boklage |first1=Charles E. |title=How New Humans Are Made: Cells and Embryos, Twins and Chimeras, Left and Right, Mind/self Soul, Sex, and Schizophrenia |date=2010 |publisher=World Scientific |isbn=978-981-283-514-7 }}{{pn|date=July 2025}}</ref>

This is particularly true for the [[marmoset]]. Recent research shows most marmosets are chimeras, sharing DNA with their [[fraternal twin]]s.<ref name="Ross2007" /> 95% of marmoset fraternal twins trade blood through [[chorionic]] fusions, making them [[hematopoietic]] chimeras.<ref name="Masahito Tachibana, Michelle Sparman and Shoukhrat Mitalipov" /><ref>{{cite journal | first1=N.| last1=Gengozian| last2=Batson| first2=JS| first3=P.| last3=Eide| title=Hematologic and Cytogenetic Evidence for Hematopoietic Chimerism in the Marmoset, Tamarinus Nigricollis| journal=Cytogenetics| year=1964| volume=10| issue=6| pages=384–393| doi=10.1159/000129828| pmid=14267132}}</ref>

In the [[budgerigar]], due to the many existing [[budgerigar colour genetics|plumage colour variations]], tetragametic chimeras can be very conspicuous, as the resulting bird will have an obvious split between two colour types{{snd}} often divided bilaterally down the centre. These individuals are known as [[half-sider budgerigar]]s.<ref name="guardian">{{cite news |last1=GrrlScientist |title=Half-siders: A tale of two birdies |url=https://www.theguardian.com/science/grrlscientist/2014/jan/31/grrlscientist-halfsider-chimera-bilateral-gynandromorph-birds |website=The Guardian |access-date=30 July 2023}}</ref>

An animal chimera is a single [[organism]] that is composed of two or more different populations of genetically distinct [[cell (biology)|cells]] that originated from different [[zygote]]s involved in [[sexual reproduction]]. If the different cells have emerged from the same zygote, the organism is called a [[Mosaic (genetics)|mosaic]]. Innate chimeras are formed from at least four parent cells (two fertilised eggs or early embryos fused together). Each population of cells keeps its own character and the resulting organism is a mixture of tissues. Cases of [[human chimera]]s have been documented.<ref name="Norton" />

====Chimerism in humans====
{{Main|Human chimera}}Some consider [[Mosaic (genetics)|mosaicism]] to be a form of chimerism,<ref>{{cite book |last1=Stewart |first1=C.L. |title=Brenner's Encyclopedia of Genetics |chapter=Chimera |date=2001 |pages=516–518 |doi=10.1016/B978-0-12-374984-0.00228-X |isbn=978-0-08-096156-9 |quote=Another form of chimera is the mosaic, which is a composite individual derived from a single fertilized egg. |quote-page=517 }}</ref> while others consider them to be distinct.<ref>{{Cite journal |last=Madan |first=Kamlesh |date=2020-09-01 |title=Natural human chimeras: A review |journal=European Journal of Medical Genetics |volume=63 |issue=9 |article-number=103971 |doi=10.1016/j.ejmg.2020.103971 |quote=A chimera is an organism whose cells are derived from two or more zygotes as opposed to a mosaic whose different cell lines are derived from a single zygote |doi-access=free |pmid=32565253 }}</ref><ref>{{cite journal |last1=Anderson |first1=D |last2=Billingham |first2=R E |last3=Lampkin |first3=G H |last4=Medawar |first4=P B |title=The use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle |journal=Heredity |date=December 1951 |volume=5 |issue=3 |pages=379–397 |doi=10.1038/hdy.1951.38 |bibcode=1951Hered...5..379A |quote=In the current embryological (which is also the classical) sense, a 'chimaera' is an organism whose cells derive from two or more distinct zygote lineages, and this is the sense which the term 'genetical chimaera' is here intended to convey. 'Genetical mosaic' is less suitable, because a mosaic is formed of the cells of a single zygote lineage. }}</ref><ref name=":0">{{cite journal |last1=Santelices |first1=B. |title=Mosaicism and chimerism as components of intraorganismal genetic heterogeneity |journal=Journal of Evolutionary Biology |date=November 2004 |volume=17 |issue=6 |pages=1187–1188 |doi=10.1111/j.1420-9101.2004.00813.x |pmid=15525401 |quote=Mosaicism originates by intrinsic genetic variations caused, among other processes, by somatic mutations, while chimerism originates from allogenic fusion or grafting. As such, chimerism is much rarer and involves a much larger genetic change than mosaicism.}}</ref> Mosaicism involves a [[mutation]] of the genetic material in a cell, giving rise to a subset of cells that are different from the rest. Natural chimerism is the fusion of more than one fertilized [[zygote]] in the early stages of [[prenatal development]]. It is much rarer than mosaicism.<ref name=":0" />

In artificial chimerism, an individual has one [[cell lineage]] that was inherited genetically at the time of the formation of the human embryo and the other that was introduced through a procedure, including [[organ transplantation]] or [[blood transfusion]].<ref>{{Cite journal |last=Rinkevich |first=B. |date=June 2001 |title=Human natural chimerism: an acquired character or a vestige of evolution? |journal=Human Immunology |volume=62 |issue=6 |pages=651–657 |doi=10.1016/s0198-8859(01)00249-x |pmid=11390041 }}</ref> Specific types of transplants that could induce this condition include bone marrow transplants and organ transplants, as the recipient's body essentially works to permanently incorporate the new blood stem cells into it.

Boklage argues that many human 'mosaic' cell lines will be "found to be chimeric if properly tested".<ref>{{cite journal |last1=Boklage |first1=Charles E. |title=Embryogenesis of chimeras, twins and anterior midline asymmetries |journal=Human Reproduction |date=March 2006 |volume=21 |issue=3 |pages=579–591 |doi=10.1093/humrep/dei370 |pmid=16253966 |doi-access=free }}</ref>

In contrast, a human where each cell contains human genetic material as well as that from another species would be a [[human–animal hybrid]].<ref name="Taddeo Robert Hybrids and Chimeras"/>

While German [[dermatologist]] [[Alfred Blaschko]] described [[Blaschko's lines]] in 1901, the genetic science took until the 1930s to approach a vocabulary for the phenomenon.{{fact|date=July 2025}} The term ''genetic chimera'' has been used at least since the 1944 article of [[:ru:Бельговский, Марк Леонидович|Belgovskii]].<ref name="belgovskii44">{{cite journal |last1=Бельговский |first1=Марк Леонидович |title=К вопросу о механизме осуществления мозаичности, связанной с гетерохроматическими районами хромосом |language=ru |journal=Журнал общей биологии |volume=5 |issue=6 |date=1944 |pages=325–356 }} Translated as: {{cite book |last1=Belgovskii |first1=M. L. |date=1962 |title=The Causes of Mosaicism Associated With Heterochromatic Chromosome Regions |id=OTS 61-11476 |hdl=2027/mdp.39015086686659 |hdl-access=free }}{{psc|date=July 2025}}</ref>

This condition is either innate or it is synthetic, acquired for example through the infusion of [[allogeneic]] [[blood cell]]s during [[Organ transplant|transplantation]] or [[Blood transfusion|transfusion]].{{citation needed|date=February 2021}}

In nonidentical twins, innate chimerism occurs by means of blood vessel [[anastomose]]s. The likelihood of offspring being a chimera is increased if it is created via [[in vitro fertilization|in vitro fertilisation]].<ref name="Strain" /> Chimeras can often breed, but the fertility and type of offspring depend on which cell line gave rise to the ovaries or testes; varying degrees of [[intersex]] differences may result if one set of cells is genetically female and another genetically male.{{citation needed|date=February 2021}}

On January 22, 2019, the [[National Society of Genetic Counselors]] released an article ''Chimerism Explained: How One Person Can Unknowingly Have Two Sets of DNA'', where they state, "where a twin pregnancy evolves into one child, is currently believed to be one of the rarer forms. However, we know that 20 to 30% of singleton pregnancies were originally a twin or a multiple pregnancy".<ref>{{Cite web|url=https://www.nsgc.org/p/bl/et/blogaid=1084|title=Chimerism Explained: How One Person Can Unknowingly Have Two Sets of DNA|website=National Society of Genetic Counselors|access-date=2020-02-02|archive-date=2020-02-02 |archive-url=https://web.archive.org/web/20200202124939/https://www.nsgc.org/p/bl/et/blogaid%3D1084|url-status=dead}}</ref>

Most human chimeras will go through life without realizing they are chimeras. The difference in phenotypes may be subtle (e.g., having a [[hitchhiker's thumb]] and a straight thumb, eyes of slightly different colors, differential hair growth on opposite sides of the body, etc.) or completely undetectable. Chimeras may also show, under a certain spectrum of UV light, distinctive marks on the back resembling that of arrow points pointing downward from the shoulders down to the lower back; this is one expression of pigment unevenness called [[Blaschko's lines]].<ref>{{cite web |url=http://www.thetech.org/genetics/ask.php?id=75 |title=Understanding Genetics: Human Health and the Genome |date=November 30, 2004 |work=Ask a Geneticist |publisher=[[Stanford University School of Medicine]] |first1=Barry |last1=Starr |archive-url=https://web.archive.org/web/20110724035334/http://www.thetech.org/genetics/ask.php?id=75 |archive-date=2011-07-24}}<!-- Date determined from list at https://web.archive.org/web/20110805030220/http://www.thetech.org/genetics/asklist.php?category=% --></ref>

{{anchor|(KarenKeegan)}}Another case was that of Karen Keegan, who was also suspected (initially) of not being her children's biological mother, after DNA tests on her adult sons for a kidney transplant she needed seemed to show that she was not their mother.<ref name="Norton" /><ref>{{cite episode |url=http://www.five.tv/programmes/extraordinarypeople/twininside/ |title=The Twin Inside Me: Extraordinary People |series=Extraordinary People |station=[[Five (TV channel)|Channel 5]] (UK) |date=9 March 2006 |archive-url=https://web.archive.org/web/20060526105634/http://www.five.tv/programmes/extraordinarypeople/twininside/ |archive-date=May 26, 2006 |url-status=dead}}</ref>

===Plants===
[[File:Starr-080117-1519-Pelargonium x hortorum-variegated leaves-Walmart Kahului-Maui (24873763676).jpg|right|thumb|upright|The green cells in the centres of the leaves of this ''[[Pelargonium]]'' plant have formed from the epithelium cell layer, which has normal chlorophyll. That cell layer does not extend all the way to the edges of the leaves, which therefore show the chlorophyll-deficient cells of other developmental layers. This is a periclinal chimera.]]

====Structure====
The distinction between sectorial, mericlinal and periclinal '''plant chimeras''' is widely used.<ref>{{cite book |last1=Kirk |first1=John Thomas Osmond |last2=Tilney-Bassett |first2=Richard A. E. |title=The Plastids, Their Chemistry, Structure, Growth, and Inheritance |date=1978 |publisher=Elsevier/North Holland Biomedical Press |isbn=978-0-444-80022-0 }}{{pn|date=July 2025}}</ref><ref>{{cite thesis |last1=van Harten |first1=A. M. |date=1978 |title=Mutation Breeding Techniques and Behaviour of Irradiated Shoot Apices of Potato |id={{CORE output|29384160}} |isbn=978-90-220-0667-2 |doi=10.18174/210958 }}{{pn|date=July 2025}}</ref> Periclinal chimeras involve a genetic difference that persists in the descendant cells of a particular [[meristem]] layer. This type of chimera is more stable than mericlinal or sectoral mutations that affect only later generations of cells.<ref>{{citation |url=https://propg.ifas.ufl.edu/03-genetic-selection/04-genetic-chimera.html |title=Chimeras |access-date=12 October 2024}}</ref>

====Graft chimeras====
{{Main|Graft-chimaera}}

[[File:Taxus-mosaic1.JPG|thumb|upright|[[Taxus]] mosaic]]

These are produced by grafting genetically different parents, different [[cultivar]]s or different species (which may belong to different genera). The tissues may be partially fused together following [[grafting]] to form a single growing organism that preserves both types of tissue in a single shoot.<ref>{{cite journal |last1=Norris |first1=R. |last2=Smith |first2=R. H. |last3=Vaughn |first3=K. C. |title=Plant Chimeras Used to Establish de novo Origin of Shoots |journal=Science |date=April 1983 |volume=220 |issue=4592 |pages=75–76 |doi=10.1126/science.220.4592.75 |pmid=17736164 |bibcode=1983Sci...220...75N }}</ref> Just as the constituent species are likely to differ in a wide range of features, so the behavior of their periclinal chimeras is like to be highly variable.<ref>{{cite book |last1=Tilney-Bassett |first1=Richard A. E. |title=Plant Chimeras |date=1991 |publisher=[[Cambridge University Press]] |isbn=978-0-521-42787-6 }}{{pn|date=July 2025}}</ref> The first such known chimera was probably the [[Bizzarria]], which is a fusion of the [[Florentine citron]] and the [[sour orange]]. Well-known examples of a graft-chimera are [[+Laburnocytisus 'Adamii'|''Laburnocytisus'' 'Adamii']], caused by a fusion of a ''[[Laburnum]]'' and a [[Broom (shrub)|broom]], and "Family" trees, where multiple varieties of apple or pear are grafted onto the same tree. Many fruit trees are cultivated by grafting the body of a sapling onto a [[rootstock]].<ref>{{Cite web|url=https://extension.unh.edu/resource/growing-fruit-grafting-fruit-trees-home-orchard-fact-sheet|title=Growing Fruit: Grafting Fruit Trees in the Home Orchard [fact sheet] {{!}} UNH Extension|website=extension.unh.edu|date=17 January 2018|language=en|access-date=2020-02-23}}</ref>

====Chromosomal chimeras====
These are chimeras in which the layers differ in their [[chromosome]] constitution. Occasionally, chimeras arise from loss or gain of individual chromosomes or chromosome fragments owing to [[cell division|misdivision]].<ref>{{cite journal |last1=Thomson |first1=James D. |last2=Herre |first2=E. A. |last3=Hamrick |first3=J. L. |last4=Stone |first4=J. L. |title=Genetic Mosaics in Strangler Fig Trees: Implications for Tropical Conservation |journal=Science |date=22 November 1991 |volume=254 |issue=5035 |pages=1214–1216 |doi=10.1126/science.254.5035.1214 |pmid=17776412 |bibcode=1991Sci...254.1214T }}</ref> More commonly cytochimeras have simple multiple of the normal chromosome complement in the changed layer. There are various effects on cell size and growth characteristics.

====Nuclear gene-differential chimeras====
These chimeras arise by spontaneous or induced mutation of a nuclear gene to a dominant or recessive allele. As a rule, one character is affected at a time in the leaf, flower, fruit, or other parts.{{Citation needed|date=January 2017}}

====Plastid gene-differential chimeras====
These chimeras arise by spontaneous or induced mutation of a plastid gene, followed by the sorting-out of two kinds of plastid during vegetative growth. Alternatively, after selfing or [[nucleic acid thermodynamics]], plastids may sort-out from a mixed egg or mixed zygote respectively. This type of chimera is recognized at the time of origin by the sorting-out pattern in the leaves. After sorting-out is complete, periclinal chimeras are distinguished from similar looking nuclear gene-differential chimeras by their [[mendelian inheritance|non-mendelian inheritance]]. The majority of variegated-leaf chimeras are of this kind.{{Citation needed|date=January 2017}}

All plastid gene- and some nuclear gene-differential chimeras affect the color of the plasmids within the leaves, and these are grouped together as [[chlorophyll]] chimeras, or preferably as variegated leaf chimeras. For most variegation, the mutation involved is the loss of the [[chloroplast]]s in the mutated tissue, so that part of the plant tissue has no green pigment and no [[Photosynthesis|photosynthetic]] ability. This mutated tissue is unable to survive on its own, but it is kept alive by its partnership with normal photosynthetic tissue. Sometimes chimeras are also found with layers differing in respect of both their nuclear and their plastid genes.{{Citation needed|date=January 2017}}

====Origins====
There are multiple reasons to explain the occurrence of plant chimera during the plant recovery stage:

# The process of shoot [[organogenesis]] starts from the multicellular origin.<ref>{{cite journal |last1=Zhu |first1=Xue-Yun |last2=Zhao |first2=Man |last3=Ma |first3=Sheng |last4=Ge |first4=Ya-Ming |last5=Zhang |first5=Ming-Fang |last6=Chen |first6=Li-Ping |title=Induction and origin of adventitious shoots from chimeras of Brassica juncea and Brassica oleracea |journal=Plant Cell Reports |date=11 September 2007 |volume=26 |issue=10 |pages=1727–1732 |doi=10.1007/s00299-007-0398-4 |pmid=17622536 |bibcode=2007PCelR..26.1727Z }}</ref>
# The endogenous tolerance leads to the ineffectiveness of the weak selective agents.
# A self-protection mechanism (cross protection). Transformed cells serve as guards to protect the untransformed ones.<ref>{{cite journal |last1=Park |first1=Sung H. |last2=Rose |first2=Susan C. |last3=Zapata |first3=Cecilia |last4=Srivatanakul |first4=Metinee |last5=Smith |first5=Roberta H. |title=Cross-protection and selectable marker genes in plant transformation |journal=In Vitro Cellular & Developmental Biology - Plant |date=April 1998 |volume=34 |issue=2 |pages=117–121 |doi=10.1007/BF02822775 |bibcode=1998IVCDB..34..117P }}</ref>
# The observable characteristic of transgenic cells may be a transient expression of the marker gene. Or it may due to the presence of agrobacterium cells.{{Citation needed|date=January 2017}}

=====Detection=====
Untransformed cells should be easy to detect and remove to avoid chimeras. This is because it is important to maintain the stable ability of the transgenic plants across different generations. Reporter genes such as [[GUS reporter system|GUS]] and [[Green Fluorescent Protein]]<ref>{{cite journal |last1=Rakosy-Tican |first1=Elena |last2=Aurori |first2=Cristian M. |last3=Dijkstra |first3=Camelia |last4=Thieme |first4=Ramona |last5=Aurori |first5=Adriana |last6=Davey |first6=Michael R. |title=The usefulness of the gfp reporter gene for monitoring Agrobacterium-mediated transformation of potato dihaploid and tetraploid genotypes |journal=Plant Cell Reports |date=May 2007 |volume=26 |issue=5 |pages=661–671 |doi=10.1007/s00299-006-0273-8 |pmid=17165042 |bibcode=2007PCelR..26..661R }}</ref> (GFP) are used in combination with plant selective markers (herbicide, antibody etc.). However, GUS expression depends on the plant development stage and GFP may be influenced by the green tissue autofluorescence. [[Quantitative PCR]] could be an alternative method for chimera detection.<ref>{{cite journal |last1=Faize |first1=Mohamed |last2=Faize |first2=Lydia |last3=Burgos |first3=Lorenzo |title=Using quantitative real-time PCR to detect chimeras in transgenic tobacco and apricot and to monitor their dissociation |journal=BMC Biotechnology |date=December 2010 |volume=10 |issue=1 |article-number=53 |doi=10.1186/1472-6750-10-53 |pmid=20637070 |pmc=2912785 |doi-access=free }}</ref>

===Viruses===
{{main|Chimera (virus)}}
[[File:Boiling Springs Lake (8553656936).jpg|thumb|upright|Boiling Springs Lake, California, is where the first natural chimeric virus was found in 2012.<ref name=diemer12 />]]

In 2012, the first example of a naturally occurring RNA-DNA hybrid virus was unexpectedly discovered during a [[metagenomic]] study of the acidic extreme environment of [[Geothermal areas in Lassen Volcanic National Park#Boiling Springs Lake|Boiling Springs Lake]] in [[Lassen Volcanic National Park]], California.<ref name=diemer12/><ref name=thompson12>{{cite journal |last1=Thompson |first1=Helen |title=Hot spring yields hybrid genome |journal=Nature |date=19 April 2012 |doi=10.1038/nature.2012.10492 }}</ref> The virus was named BSL-RDHV (Boiling Springs Lake RNA DNA Hybrid Virus).<ref name=devor12>{{cite magazine |last=Devor |first=Caitlin |date=12 July 2012 |url=https://www.jyi.org/2012-july/2012/7/12/scientists-discover-hybrid-virus |title=Scientists discover hybrid virus |magazine=Journal of Young Investigators |access-date=31 March 2020}}</ref> Its [[genome]] is related  to a DNA [[circovirus]], which usually infects birds and pigs, and a RNA [[tombusvirus]], which infect plants. The study surprised scientists, because DNA and RNA viruses vary and the way the chimera came together was not understood.<ref name=diemer12/><ref name="sdaily">{{cite web |author=BioMed Central |date=18 April 2012 |url=https://www.sciencedaily.com/releases/2012/04/120418204353.htm |title=Could a newly discovered viral genome change what we thought we knew about virus evolution? |work=ScienceDaily |access-date=March 31, 2020}}</ref>

Other viral chimeras have also been found, and the group is known as the CHIV viruses ("chimeric viruses").<ref name=koonina15>{{cite journal |last1=Fukui |first1=Akira |last2=Mitsui |first2=Tadao |title=A Contribution to the Study of the Pigmented Leukocytes in Urodeles |journal=Okajimas Folia Anatomica Japonica |date=1965 |volume=41 |issue=5 |pages=285–293 |doi=10.2535/ofaj1936.41.5_285 |pmid=5898234 |doi-access=free }}</ref>

==Research==
The first known primate chimeras are the rhesus monkey twins, Roku and Hex, each having six genomes. They were created by mixing cells from [[totipotent]] four-cell morulas; although the cells never fused, they worked together to form organs. It was discovered that one of these primates, Roku, was a sexual chimera; as four percent of Roku's blood cells contained two x chromosomes.<ref name="Masahito Tachibana, Michelle Sparman and Shoukhrat Mitalipov" />

A major milestone in chimera experimentation occurred in 1984 when a chimeric [[sheep-goat chimera|sheep–goat]] was produced by combining [[embryo]]s from a [[goat]] and a [[sheep]], and survived to adulthood.<ref>{{cite magazine | url = http://www.time.com/time/magazine/article/0,9171,921546,00.html | archive-url = https://web.archive.org/web/20080216005102/http://www.time.com/time/magazine/article/0,9171,921546,00.html | url-status = dead | archive-date = February 16, 2008 | title = It's a Geep | magazine = [[Time (magazine)|Time]] | date = 27 February 1984 | access-date = 4 January 2012}}</ref>

To research the developmental biology of the bird embryo, researchers produced artificial quail-chick chimeras in 1987. By using transplantation and [[ablation]] in the chick embryo stage, the neural tube and the neural crest cells of the chick were ablated, and replaced with the same parts from a quail.<ref>{{Cite web|url=https://www.sdbonline.org/sites/archive/dbcinema/ledouarin/ledouarin.html|title=Developmental Biology Cinema, Le Douarin|website=sdbonline.org|access-date=2020-04-10}}</ref> Once hatched, the quail feathers were visibly apparent around the wing area, whereas the rest of the chick's body was made of its own chicken cells.

In August 2003, researchers at the [[Shanghai Second Medical University]] in China reported that they had successfully fused human skin cells and [[rabbit]] ova to create the first human chimeric embryos. The embryos were allowed to develop for several days in a laboratory setting, and then destroyed to harvest the resulting [[stem cell]]s.<ref>{{cite news | url=http://news.nationalgeographic.com/news/2005/01/0125_050125_chimeras.html| archive-url=https://web.archive.org/web/20050127063859/http://news.nationalgeographic.com/news/2005/01/0125_050125_chimeras.html| url-status=dead| archive-date=January 27, 2005| title=Animal-Human Hybrids Spark Controversy| last=Mott| first=Maryann| date=January 25, 2005| work=National Geographic News}}</ref> In 2007, scientists at the [[University of Nevada, Reno|University of Nevada]] School of Medicine created a sheep whose blood contained 15% human cells and 85% sheep cells.<ref>{{Cite journal |last1=Almeida-Porada |first1=Graça |last2=Porada |first2=Christopher |last3=Gupta |first3=Nicole |last4=Torabi |first4=Ali |last5=Thain |first5=David |last6=Zanjani |first6=Esmail D. |date=October 2007 |title=The human–sheep chimeras as a model for human stem cell mobilization and evaluation of hematopoietic grafts' potential |journal=Experimental Hematology |language=en |volume=35 |issue=10 |pages=1594–1600 |doi=10.1016/j.exphem.2007.07.009 |pmid=17889724 |pmc=2048750 }}</ref>

In 2023 a study reported the first chimeric monkey using embryonic stem cell lines, it was the only live birth from 12 pregnancies resulting from 40 implanted embryos of the [[crab-eating macaque]], an average of 67% and a highest of 92% of the cells across the 26 tested tissues were descendants of the donor stem cells against 0.1–4.5% from previous experiments on chimeric monkeys.<ref>{{Cite journal |last1=Cao |first1=Jing |last2=Li |first2=Wenjuan |last3=Li |first3=Jie |last4=Mazid |first4=Md. Abdul |last5=Li |first5=Chunyang |last6=Jiang |first6=Yu |last7=Jia |first7=Wenqi |last8=Wu |first8=Liang |last9=Liao |first9=Zhaodi |last10=Sun |first10=Shiyu |last11=Song |first11=Weixiang |last12=Fu |first12=Jiqiang |last13=Wang |first13=Yan |last14=Lu |first14=Yong |last15=Xu |first15=Yuting |date=November 2023 |title=Live birth of chimeric monkey with high contribution from embryonic stem cells |journal=Cell |language=en |volume=186 |issue=23 |pages=4996–5014.e24 |doi=10.1016/j.cell.2023.10.005|doi-access=free |pmid=37949056 }}</ref><ref>{{cite journal |last1=Wong |first1=Carissa |title=This hybrid baby monkey is made of cells from two embryos |journal=Nature |date=16 November 2023 |volume=623 |issue=7987 |pages=468–469 |doi=10.1038/d41586-023-03473-w |pmid=37945704 |bibcode=2023Natur.623..468W }}</ref><ref>{{Cite web |title=First live birth of a chimeric monkey using embryonic stem cell lines |url=https://www.eurekalert.org/news-releases/1006802 |access-date=2023-11-16 |website=EurekAlert! |language=en}}</ref>

===Work with mice===
[[File:ChimericMouseWithPups.jpg|thumb|upright|A chimeric mouse with her [[offspring]], which carry the [[w:Agouti gene|agouti coat color gene]]; note her pink eye]]

Chimeric mice are important animals in biological research, as they allow for the investigation of a variety of biological questions in an animal that has two distinct genetic pools within it. These include insights into problems such as the tissue specific requirements of a gene, cell lineage, and cell potential.

The general methods for creating chimeric mice can be summarized either by injection or aggregation of embryonic cells from different origins. The first chimeric mouse was made by [[Beatrice Mintz]] in the 1960s through the aggregation of eight-cell-stage embryos.<ref>{{cite journal |last1=Mintz |first1=B. |last2=Silvers |first2=W. K. |title='Intrinsic' Immunological Tolerance in Allophenic Mice |journal=Science |volume=158 |issue=3807 |pages=1484–6 |year=1967 |doi=10.1126/science.158.3807.1484 |pmid=6058691 |bibcode=1967Sci...158.1484M }}</ref> Injection on the other hand was pioneered by Richard Gardner and Ralph Brinster who injected cells into blastocysts to create chimeric mice with germ lines fully derived from injected [[embryonic stem cells]] (ES cells).<ref>{{cite journal |doi=10.1016/0168-9525(86)90161-7 |last1=Robertson |first1=EJ |year=1986 |title=Pluripotential stem cell lines as a route into the mouse germ line |journal=Trends Genet |volume=2 |pages=9–13}}</ref> Chimeras can be derived from mouse embryos that have not yet implanted in the uterus as well as from implanted embryos. ES cells from the inner cell mass of an implanted blastocyst can contribute to all cell lineages of a mouse including the germ line. ES cells are a useful tool in chimeras because genes can be mutated in them through the use of [[homologous recombination]], thus allowing [[gene targeting]]. Since this discovery occurred in 1988, ES cells have become a key tool in the generation of specific chimeric mice.<ref>{{cite journal |last1=Doetschman |first1=T |last2=Maeda |first2=N |last3=Smithies |first3=O |title=Targeted mutation of the Hprt gene in mouse embryonic stem cells |journal=Proceedings of the National Academy of Sciences |date=November 1988 |volume=85 |issue=22 |pages=8583–8587 |doi=10.1073/pnas.85.22.8583 |pmid=3186749 |pmc=282503 |bibcode=1988PNAS...85.8583D |doi-access=free }}</ref>

====Underlying biology====
The ability to make mouse chimeras comes from an understanding of early mouse development. Between the stages of fertilization of the egg and the implantation of a blastocyst into the uterus, different parts of the mouse embryo retain the ability to give rise to a variety of cell lineages. Once the embryo has reached the blastocyst stage, it is composed of several parts, mainly the [[trophectoderm]], the [[inner cell mass]], and the [[primitive endoderm]]. Each of these parts of the blastocyst gives rise to different parts of the embryo; the inner cell mass gives rise to the embryo proper, while the trophectoderm and primitive endoderm give rise to extra embryonic structures that support growth of the embryo.<ref>{{cite journal |last1=Ralston |first1=A |last2=Rossant |first2=J |title=Genetic regulation of stem cell origins in the mouse embryo |journal=Clinical Genetics |date=August 2005 |volume=68 |issue=2 |pages=106–112 |doi=10.1111/j.1399-0004.2005.00478.x |pmid=15996204 }}</ref> Two- to eight-cell-stage embryos are competent for making chimeras, since at these stages of development, the cells in the embryos are not yet committed to give rise to any particular cell lineage, and could give rise to the inner cell mass or the trophectoderm. In the case where two diploid eight-cell-stage embryos are used to make a chimera, chimerism can be later found in the [[epiblast]], primitive [[endoderm]], and trophectoderm of the mouse [[blastocyst]].<ref>{{cite journal |last1=Tam |first1=Patrick P. L. |last2=Rossant |first2=Janet |title=Mouse embryonic chimeras: tools for studying mammalian development |journal=Development |date=22 December 2003 |volume=130 |issue=25 |pages=6155–6163 |doi=10.1242/dev.00893 |pmid=14623817 }}</ref><ref>{{cite journal |last1=Rossant |first1=J. |title=Postimplantation development of blastomeres isolated from 4- and 8-cell mouse eggs |journal=Journal of Embryology and Experimental Morphology |date=October 1976 |volume=36 |issue=2 |pages=283–290 |pmid=1033982 }}</ref>

It is possible to dissect the embryo at other stages so as to accordingly give rise to one lineage of cells from an embryo selectively and not the other. For example, subsets of blastomeres can be used to give rise to chimera with specified cell lineage from one embryo. The Inner Cell Mass of a diploid blastocyst, for example, can be used to make a chimera with another blastocyst of eight-cell diploid embryo; the cells taken from the inner cell mass will give rise to the primitive endoderm and to the epiblast in the chimera mouse.<ref>{{cite book |last1=Papaioannou |first1=Virginia |last2=Johnson |first2=Randall |title=Gene Targeting |chapter=Production of chimeras by blastocyst and morula injection of targeted ES cells |date=1999 |doi=10.1093/oso/9780199637928.003.0008 |isbn=978-0-19-963792-8 }}</ref>

From this knowledge, [[ES cell]] contributions to chimeras have been developed. ES cells can be used in combination with eight-cell-and two-cell-stage embryos to make chimeras and exclusively give rise to the embryo proper. Embryos that are to be used in chimeras can be further genetically altered to specifically contribute to only one part of chimera. An example is the chimera built off of ES cells and tetraploid embryos, which are artificially made by electrofusion of two two-cell diploid embryos. The tetraploid embryo will exclusively give rise to the trophectoderm and primitive endoderm in the chimera.<ref>{{cite journal |last1=Kubiak |first1=Jacek Z. |last2=Tarkowski |first2=Andrzej K. |title=Electrofusion of mouse blastomeres |journal=Experimental Cell Research |date=April 1985 |volume=157 |issue=2 |pages=561–566 |doi=10.1016/0014-4827(85)90143-0 |pmid=3884349 }}</ref><ref>{{cite book |last1=Nagy |first1=Andras |last2=Rossant |first2=Janet |title=Gene Targeting |chapter=Production and analysis of ES cell aggregation chimeras |date=1999 |doi=10.1093/oso/9780199637928.003.0009 |isbn=978-0-19-963792-8 }}</ref>

====Methods of production====
There are a variety of combinations that can give rise to a successful chimera mouse and{{snd}} according to the goal of the experiment{{snd}} an appropriate cell and embryo combination can be picked; they are generally but not limited to diploid embryo and ES cells, diploid embryo and diploid embryo, ES cell and tetraploid embryo, diploid embryo and tetraploid embryo, ES cells and ES cells. The combination of embryonic stem cell and diploid embryo is a common technique used for the making of chimeric mice, since gene targeting can be done in the embryonic stem cell. These kinds of chimeras can be made through either aggregation of stem cells and the diploid embryo or injection of the stem cells into the diploid embryo. If embryonic stem cells are to be used for gene targeting to make a chimera, the following procedure is common: a construct for homologous recombination for the gene targeted will be introduced into cultured mouse embryonic stem cells from the donor mouse, by way of electroporation; cells positive for the recombination event will have antibiotic resistance, provided by the insertion cassette used in the gene targeting; and be able to be positively selected for.<ref>{{cite journal | doi = 10.1073/pnas.93.17.8804 | last1 = Jasin | first1 = M | last2 = Moynahan | first2 = ME | last3 = Richardson | first3 = C | year = 1996 | title = Targeted transgenesis | journal = PNAS | volume = 93 | issue = 17| pages = 8804–8808 | pmid = 8799106 | pmc = 38547 | bibcode = 1996PNAS...93.8804J| doi-access = free }}</ref><ref>{{cite journal | doi = 10.1017/S0958067000021059 | last1 = Ledermann | first1 = B | year = 2000 | title = Embryonic Stem Cell and Gene Targeting | journal = Experimental Physiology | volume = 85 | issue = 6| pages = 603–613 | article-number = S0958067000021059 | pmid = 11187956| doi-access = free }}</ref> ES cells with the correct targeted gene are then injected into a diploid host mouse blastocyst. Then, these injected blastocysts are implanted into a pseudo pregnant female surrogate mouse, which will bring the embryos to term and give birth to a mouse whose germline is derived from the donor mouse's ES cells.<ref>Chimera Mouse production by blastocyst injection, Wellcome trust Sanger Institute, http://www.eucomm.org/docs/protocols/mouse_protocol_1_Sanger.pdf{{dead link|date=July 2025}}</ref> This same procedure can be achieved through aggregation of ES cells and diploid embryos, diploid embryos are cultured in aggregation plates in wells where single embryos can fit, to these wells ES cells are added the aggregates are cultured until a single embryo is formed and has progressed to the blastocyst stage, and can then be transferred to the surrogate mouse.<ref>{{cite book |last1=Tanaka |first1=Mika |last2=Hadjantonakis |first2=Anna-Katerina |last3=Nagy |first3=Andras |title=Gene Knockout Protocols |chapter=Aggregation Chimeras: Combining ES Cells, Diploid and Tetraploid Embryos |series=Methods in Molecular Biology |date=2001 |volume=158 |pages=135–154 |doi=10.1385/1-59259-220-1:135 |pmid=11236654 |isbn=1-59259-220-1 }}</ref>

==Ethics and legislation==
{{See also|Bioethics}}

The US and Western Europe have strict codes of ethics and regulations in place that expressly forbid certain subsets of experimentation using human cells, though there is a vast difference in the regulatory framework.<ref>Futehally, Ilmas, Beyond Biology, [[Strategic Foresight Group]] [http://www.strategicforesight.com/inner-articles.php?id=77#.UyZHJ1GSxv0]</ref> Through the creation of human chimeras comes the question: where does society now draw the line of humanity? This question poses serious legal and moral issues, along with creating controversy. Chimpanzees, for example, are not offered any legal standing, and are [[Animal euthanasia|euthanised]] if they pose a threat to humans. If a chimpanzee is genetically altered to be more similar to a human, it may blur the ethical line between animal and human. Legal debate would be the next step in the process to determine whether certain chimeras should be granted legal rights.<ref>{{cite web| last1=Bruch| first1=Quinton| title=Defining Humanity: The Ethics of Chimeric Animals and Organ Growing| url=http://triplehelixblog.com/2014/02/defining-humanity-the-ethics-of-chimeric-animals-and-organ-growing/| website=The Triple Helix Online| access-date=21 May 2015| date=2014-02-20| archive-date=2015-06-05| archive-url=https://web.archive.org/web/20150605080030/http://triplehelixblog.com/2014/02/defining-humanity-the-ethics-of-chimeric-animals-and-organ-growing/| url-status=usurped}}</ref> Along with issues regarding the rights of chimeras, individuals have expressed concern about whether or not creating human chimeras diminishes the "dignity" of being human.<ref name="Human Chimera Prohibition Act" />

==See also==
* [[46,XX/46,XY]]
* [[CAR T cell]]
* [[Fusion protein]]
* [[Genetic chimerism in fiction]]
* [[Polycephaly]]
* [[Retron]]
* [[Vanishing twin]]
* [[X-inactivation]] (lyonization)

==References==
{{reflist|refs=
<ref name="Norton">{{cite journal |last1=Norton |first1=Aaron T. |last2=Zehner |first2=Ozzie |title=Which Half is Mommy?: Tetragametic Chimerism and Trans-Subjectivity |journal=WSQ: Women's Studies Quarterly |date=September 2008 |volume=36 |issue=3–4 |pages=106–125 |doi=10.1353/wsq.0.0115 }}</ref>
<ref name="Masahito Tachibana, Michelle Sparman and Shoukhrat Mitalipov">{{cite journal |journal=Cell |title=Generation of Chimeric Rhesus Monkeys |author=Masahito Tachibana, Michelle Sparman and [[Shoukhrat Mitalipov]] |date=January 2012 |pmc=3264685 |pmid=22225614 |doi=10.1016/j.cell.2011.12.007 |volume=148 |issue=1–2 |pages=285–95}}</ref>
<ref name="Ross2007">{{cite journal |last=Ross |first=C. N. |author2=J. A. French |author3=G. Orti |year=2007 |title=Germ-line chimerism and paternal care in marmosets (Callithrix kuhlii) |journal=Proceedings of the National Academy of Sciences |volume=104 |issue=15 |pages=6278–6282 |pmid=17389380 |pmc=1851065 |doi=10.1073/pnas.0607426104 |bibcode=2007PNAS..104.6278R |doi-access=free }}</ref>
<ref name="Strain">{{cite journal |last=Strain |first=Lisa |author2=John C.S. Dean |author3=Mark P. R. Hamilton |author4=David T. Bonthron |year=1998 |title=A True Hermaphrodite Chimera Resulting from Embryo Amalgamation after in Vitro Fertilization |journal=The New England Journal of Medicine |volume=338 |issue=3 |pages=166–169 |doi=10.1056/NEJM199801153380305 |pmid=9428825|doi-access=free }}</ref>
<!--<ref name="IndepBoneMarrow">{{cite web |url=https://www.independent.co.uk/news/world/americas/dna-bone-marrow-transplant-man-chimera-chris-long-forensic-science-police-a9238636.html |title=Man who had transplant finds out months later his DNA has changed to that of donor 5,000 miles away |work=[[The Guardian]] |access-date=December 12, 2019 |first=Heather |last=Murphy|date=2019-12-09}}</ref>-->
<ref name="Blanquer,A">{{cite journal |last1=Blanquer |first1=Andrea |last2=Uriz |first2=Maria-J. |title='Living Together Apart': The Hidden Genetic Diversity of Sponge Populations |journal=Molecular Biology and Evolution |date=September 2011 |volume=28 |issue=9 |pages=2435–2438 |doi=10.1093/molbev/msr096 |pmid=21498599 |doi-access=free |hdl=10261/46231 |hdl-access=free }}</ref>
<ref name=diemer12>{{cite journal |last1=Diemer |first1=Geoffrey S |last2=Stedman |first2=Kenneth M |title=A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses |journal=Biology Direct |date=2012 |volume=7 |issue=1 |pages=13 |doi=10.1186/1745-6150-7-13 |doi-access=free |pmid=22515485 |pmc=3372434 }}</ref>
<ref name="Human Chimera Prohibition Act">{{cite web |title=S.659 - 109th Congress (2005-2006): A bill to amend title 18, United States Code, to prohibit human chimeras |url=https://www.congress.gov/bill/109th-congress/senate-bill/659 |website=www.congress.gov |date=17 March 2005 }}</ref>
}}

==Further reading==
* {{cite journal |vauthors=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| doi-access=free }}
* Appel, Jacob M. "The Monster's Law", ''[[Genewatch]]'', Volume 19, Number 2, March–April 2007.
* 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). [https://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''] {{Webarchive|url=https://web.archive.org/web/20121025021443/http://pqasb.pqarchiver.com/washingtonpost/access/383989051.html?dids=383989051%3A383989051&FMT=ABS&FMTS=ABS%3AFT&fmac=&date=Aug%2014%2C%202003&author=Rick%20Weiss&desc=Cloning%20Yields%20Human-Rabbit%20Hybrid%20Embryo |date=2012-10-25 }}. ''[[The Washington Post]]''.
* Weiss, Rick (February 13, 2005). [https://www.washingtonpost.com/wp-dyn/articles/A19781-2005Feb12.html ''U.S. Denies Patent for a too-human hybrid'']. ''[[The Washington Post]]''.
* {{cite journal |last1=Repas-Humpe |first1=L. M. |last2=Humpe |first2=A. |last3=Lynen |first3=R. |last4=Glock |first4=B. |last5=Dauber |first5=E. M. |last6=Simson |first6=G. |last7=Mayr |first7=W. R. |last8=Köhler |first8=M. |last9=Eber |first9=S. |title=A dispermic chimerism in a 2-year-old Caucasian boy |journal=Annals of Hematology |date=22 September 1999 |volume=78 |issue=9 |pages=431–434 |doi=10.1007/s002770050543 |pmid=10525832 }}
* {{cite journal | last1=Strain | first1=Lisa | last2=Dean | first2=John C.S. | last3=Hamilton | first3=Mark P.R. | last4=Bonthron | first4=David T. | title=A True Hermaphrodite Chimera Resulting from Embryo Amalgamation after in Vitro Fertilization | journal=New England Journal of Medicine | volume=338 | issue=3 | pages=166–9 | year=1998 | pmid=9428825 | doi=10.1056/NEJM199801153380305 | doi-access=free }}
* {{Cite book |editor1-first=David Albert |editor1-last=Jones |editor2-first=Calum |editor2-last=MacKellar |year=2012 |title=Chimera's Children: Ethical, Philosophical and Religious Perspectives on Human-Nonhuman Experimentation |location=London |publisher=Continuum Books |isbn=9781441195807 }}

==External links==
{{Commons category|Chimera (genetics)}}
* [https://www.damninteresting.com/curio/the-not-so-legendary-chimera/ "Chimerism Explained"]
* {{cite web |url=http://ghr.nlm.nih.gov/glossary=chimerism |url-status=dead |archive-url=https://web.archive.org/web/20081219202559/http://ghr.nlm.nih.gov/glossary=chimerism |archive-date=2008-12-19 |title=Chimerism |work=Genetic Home Reference |publisher=U.S. National Library of Medicine, National Institute of Health}}
* [https://web.archive.org/web/20130807094832/http://generalhorticulture.tamu.edu/HORT604/LectureSuppl/AnatomyChimeras/AnatomyChimeras05.htm Chimera: Apical Origin, Ontogeny and Consideration in Propagation]
* [http://aggie-horticulture.tamu.edu/tisscult/chimeras/chimera.html Plant Chimeras in Tissue Culture] {{Webarchive|url=https://web.archive.org/web/20131003205758/http://aggie-horticulture.tamu.edu/tisscult/chimeras/chimera.html |date=2013-10-03 }}
* Ainsworth, Claire (November 15, 2003). [https://www.newscientist.com/article.ns?id=mg18024215.100 "The Stranger Within"]. ''[[New Scientist]]'' {{subscription required}} {{Webarchive|url=https://web.archive.org/web/20081022063630/http://www.newscientist.com/article.ns?id=mg18024215.100 |date=2008-10-22 }}. (Reprinted [http://www.katewerk.com/chimera.html here])
* {{cite journal |last1=Boklage |first1=Charles E. |title=Embryogenesis of chimeras, twins and anterior midline asymmetries |journal=Human Reproduction |date=March 2006 |volume=21 |issue=3 |pages=579–591 |doi=10.1093/humrep/dei370 |pmid=16253966 }}
* {{cite journal |last1=Madan |first1=Kamlesh |title=Natural human chimeras: A review |journal=European Journal of Medical Genetics |date=September 2020 |volume=63 |issue=9 |article-number=103971 |doi=10.1016/j.ejmg.2020.103971 |pmid=32565253 |doi-access=free }}

{{Twin conditions}}
{{Authority control}}

{{DEFAULTSORT:Chimera (Genetics)}}
[[Category:Reproduction]]
[[Category:Intersex healthcare]]
[[Category:Genetic anomalies]]
[[Category:Twin]]
[[Category:Chimerism| ]]