In genetics, a chimera is an individual with 2 or more distinct, unrelated genetic lineages (ie, 46XX/46XX, 46XX/46XY, or 46XY/46XY). This condition is not to be confused with germline mosaicism, in which a mutation occurs during mitosis, altering part of a genetic line (aneuploidy). In mosaics, typically transcription errors result in a chromosome that may be either duplicated or deleted. The mutated cell is further copied, appearing separate from other cells (46XX/47XX or 46XY/47XY) but in fact, a single lineage exists. An individual with germline mosaicism shouldn’t have any related health issues since it is not a systemic mutation. An example of mosaicism where a systemic mutation exists is Trisomy 21, or Down’s syndrome, where a duplicating error occurs on chromosome 21 affecting all or nearly every cell.
Chimeras can be classified into 2 broad categories: natural or artificial. An artificial chimera is an individual who has 2 distinct genetic lineages, of which 1 was introduced deliberately. A few examples include blood transfusions, organ transplants, and bone marrow transplants. In these cases, one would expect to find disparate genetic lines.
There is a higher complexity that gives rise to the bizarre origins of natural chimeras. A tetragametic chimera is one such example. As the name suggests, a tetragametic chimera arises from 4 gametes: 2 ova fertilized by 2 sperm, resulting in dizygotic twins. During the first trimester, the 2 zygotes fuse into 1 individual. There is some dispute over the exact nature of this process. In cases of monochorionic twins, it is easy to conceptualize twin absorption, while with dichorionic twins, this explanation is more complicated. Differentiation is another process believed to give rise to a chimera singleton. It has been suggested that in utero, dizygotic twins may have some comingling of blood and that fetal blood has progenitor qualities that differentiate into other tissues. But this hypothesis alone cannot encompass the entirety of this curious condition. One such case is of a boy with an undescended, deformed testicle that was thought to be malignant. Upon a pathological examination, it was determined to be female genitalia. Whether chimarism results from twin absorption or differentiation, or possibly a mixture of both, the remaining singleton has 2 disparate genetic lineages.
Chimeras may have distinct, identifiable features. They may be born with different color eyes or different shades of patchy skin, their hair might be mixed in color or texture, or they may be born hermaphroditic. With physical indicators like these, extensive testing might reveal the presence of disparate DNA, but more often a chimera appears outwardly normal.
Once thought to be a rarity, tetragametic chimerism may be common, and with modern fertilization techniques even more so. With estimates of 12% to 15% of all births thought to originate from twin embryogenesis, and with approximately 11 singleton births per every twin birth, the potential frequency is staggering. Often their discovery is by mere coincidence when all other explanations have been exhausted. Multiple cases exist where a mother’s DNA test was believed to indicate her children couldn’t be biologically related. In one such instance, a mother was accused of defrauding the government. The state was poised to take her children away. She was pregnant at the time so the state ordered a witness to be present during the birth. At first the results only bolstered the state’s argument that she was a surrogate, but more extensive testing was done and her chimeric condition was identified.
Instances of maternal and fetal chimerism are stranger still. Maternal chimerism occurs when a small number of the mother’s cells pass through the placenta. The reason this happens is not fully understood. Some suggest that it helps keep a developing fetus healthy or aids in repairing damaged tissue. As maternal cells cross the placental barrier, they transdifferentiate into other kinds of cells the fetus may need. While examining babies who died from neonatal lupus, one researcher discovered that their hearts contained cells that could have only come from their mothers. In fetal chimerism, it is the baby’s cells that pass to the mother. Many believe this may play a role in preventing the mother’s immune system from rejecting the fetus. Having the mother’s own immune system recognize the child’s DNA as something native may be key in preventing a graft-versus-host type of scenario.
To some extent, we may all be chimeras, and everyone may be teeming with disparate genetic materials. When small amounts of genetic material exist within an individual, it is generally referred to as microchimerism. Studies have shown that women may harbor cells from their mothers, albeit small amounts, for decades. Couple that with cells from their children, and a remote possibility can be imagined where a fetus may receive cells from their mothers, grandmothers, and older siblings. A person may be walking around with 4 or more distinct genetic lineages within them.
Fetal cells may persist in mothers for decades as well, differentiating into skin, heart, blood, brain, or other tissues. This may be associated with some autoimmune diseases that mothers experience postpartum, for instance, Graves’ disease or postpartum thyroiditis. Because of the nature of fetal cell differentiation in mothers, there may be an association with other late-life autoimmune diseases as well, but further research needs to be done. If microchimerism is as pervasive as some suggest, the field of immunology and years of conventional wisdom may have to be reassessed.
- Amor D, Delatycki MB, Susman M, et al. 46,XX/46,XY at amniocentesis in a fetus with true hermaphroditism. J Med Genet. 1999;36(11):866-869. http://jmg.highwire.org/content/36/11/866.full.
- Arcabascio C. Chimeras: double the DNA-double the fun for crime scene investigators, prosecutors, and defense attorneys? Akron Law Review. 2007;40:435-464.
- Boklage CE. Embryogenesis of chimeras, twins and anterior midline asymmetries. Hum Reprod. 2006;21(3):579-591. http://humrep.oxfordjournals.org/content/21/3/579.short.
- Cho D, Lee SK, Yazer MH. A dispermic chimera with mixed field blood group B and mosaic 46,XY/47,XYY karyotype. J Korean Med Sci. 2007;22(3):553-556. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693654/.
- Eikmans M, Claas FHJ. HLA-targeted cell sorting of microchimeric cells opens the way to phenotypical and functional characterization. Chimerism. 2011;2(4):114-116. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321882/.
- Galofré JC, Davies TF. Microchimerism and thyroid disease. Hot Thyroidology. 2007; no. 2. http://www.hotthyroidology.com/editorial_174.html.
- Germline mosaicism. Inherited Health. May 29, 2009. http://www.inheritedhealth.com/info/condition.aspx?topic=162.
- Knoll JHM. Chimerism: an interesting topic and an interesting case! September 2003. http://www.cytognomix.org/presentations/ChimerismAABB9_03.pdf.
- Landy HJ, Keith LG. The vanishing twin: a review. Hum Reprod Update. 1998;4(2):177-183. http://humupd.oxfordjournals.org/content/4/2/177.full.pdf.
- Loh Y-H, Agarwal S, Park I-H. Generation of induced pluripotent stem cells from human blood. Blood. 2009;113(22):5476-5479. http://bloodjournal.hematologylibrary.org/content/113/22/5476.full.pdf+html.
- Norton AT, Zehner O. Which half is mommy? Tetragametic chimerism and trans-subjectivity. Women’s Studies Quarterly. 2008;36(3/4):106-125. http://www.jstor.org/discover/10.2307/27649788?uid=3739808&uid=2129&uid=2&uid=70&uid=4&uid=3739256&sid=56292671893.
- Saleh O. Late onset Tay-Sachs disease presenting as a brief psychotic disorder with catatonia: a case report and review of literature. Jefferson J Psychiatr. http://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1425&context=jeffjpsychiatry.
- Strain L, Dean JCS, Hamilton MPR, Bonthron DT. A true hermaphrodite chimera resulting from embryo amalgamation after in vitro fertilization. N Engl J Med. 1998;338:166-169. http://www.nejm.org/doi/full/10.1056/NEJM199801153380305.
- The stranger within. New Scientist. 2003;180(2421):34. http://www.katewerk.com/chimera.html.
- The twin inside me—chimera. My Multiple Sclerosis. March 29, 2012. http://www.mymultiplesclerosis.co.uk/misc/chimera.html.
- Van Dijk B, Boomsma DI, de Man AJ. Blood group chimerism in human multiple births is not rare. Am J Med Genet. 1996;22;61(3):264-268.