Chimerism: People With Two Sets of DNA

If you've ever swabbed your cheek for an ancestry kit, you probably assumed the result described all of you. For most people it does. A small number of people, though, are chimeras: one person whose body holds two genetically distinct cell lines. A cheek swab can capture one set of DNA while another part of the body carries a different one. That is how one woman was told she wasn't the mother of the children she gave birth to. It is also why DNA, as reliable as it is, does not always tell the whole story.

What chimerism is

A chimera is a single person whose cells come from two different genetic sources. Each line of cells is complete and working. They simply don't match each other. Depending on where a sample is taken, a lab may find one profile, the other, or both.

Nobody knows how common this is. Researchers describe chimerism as rare, but most chimeras are never detected, so its true frequency is unknown. People get tested when something has already gone wrong, such as a failed family match before a transplant or a paternity result that makes no sense. Nobody screens the general population for it, so the cases on record are the ones that happened to surface.

A person can become a chimera in several ways:

• Fused twin embryos: two embryos merge very early and grow into one person.
• Shared blood in the womb: twins whose blood vessels connect can exchange cells.
• Transplants and transfusions: a bone marrow transplant, an organ transplant or a blood transfusion brings in another person's cells.
• Pregnancy: fetal cells can circulate in the mother's body.

The first route has produced the most dramatic cases.

How twin embryos fuse: tetragametic chimerism

The technical name is tetragametic chimerism. "Tetra" means four, and "gametes" are eggs and sperm. Four sex cells are involved: two eggs, each fertilized by a different sperm. In a typical pregnancy that would produce fraternal twins. Here, the two early embryos fuse into one embryo, which develops into a single person.

One common explanation starts with hyperovulation, meaning a woman releases two eggs in the same cycle instead of one. Each egg is fertilized by a different sperm, and the two embryos fuse. A 2022 review in Frontiers in Genetics describes this tetragametic route as "by far the most common mechanism" among chimera cases that have been analyzed at the molecular level.

These cases are sometimes linked to the "vanishing twin," the idea that a twin was absorbed early in pregnancy. That description fits loosely at best. The fusion happens so early that there was never a separate twin to lose. The two embryos simply became one person. The phrase also shouldn't be read as the explanation for every chimera, since some arise in other ways.

Most chimeras never find out, because nothing looks unusual. Both cell lines are human, both work, and the person develops normally. One line often dominates, and the second may show up only in certain tissues. In one well-known case, the second line was found only in the cervix. Routine blood tests and cheek swabs can miss the second line entirely. Usually it takes a DNA test with high stakes, such as an organ match or a court case, to reveal it.

Karen Keegan

In the late 1990s, Karen Keegan was 52 and needed a kidney transplant. Her family was tested as possible donors, which is standard practice because close relatives are often the best matches. The results were baffling. According to McGill University's Office for Science and Society, the tests indicated she was not the mother of two of her three sons. She had carried and delivered all of them.

Further testing explained it. Keegan's blood carried one DNA profile. Her hair, skin, mouth cells and preserved tissue showed a second one. She was a chimera, and her sons had inherited DNA from the cell line that her blood didn't reveal.

She had shown no obvious signs and had no idea until the testing. Her case was described in the New England Journal of Medicine in an article dated May 16, 2002. That report soon mattered a great deal to a stranger on the other side of the country.

Lydia Fairchild

In 2002, Lydia Fairchild applied for public assistance in Washington State. As part of the process, DNA tests were run on her children. The children matched their father, Jamie Townsend. They did not match her.

Prosecutors suspected welfare fraud. To rule out a lab mistake, three cheek-swab tests were done, and each one excluded Fairchild as the mother. She was accused of a surrogacy scheme, in effect of claiming someone else's children as her own, and prosecutors asked that her children be placed in foster care.

Fairchild was pregnant a third time while this was going on. The judge ordered a court officer to witness the birth so there could be no doubt about who delivered the baby. The newborn was tested too, and the results again showed no match with the mother the officer had just watched give birth.

Her lawyer, Alan Tindell, found the published Keegan report and recognized the possibility. Fairchild's hair, cheek, skin and blood all showed one genetic lineage. A cervical sample showed a second lineage, and that one matched her children. The case was dismissed.

The case shows how easily chimerism can go undetected. The usual samples taken for a DNA test (cheek, blood, hair) all agreed with one another and were all misleading. Only tissue from a part of the body tied to reproduction showed the DNA she had passed to her children.

Other ways to become a chimera

Being born from fused embryos isn't the only route. A person can also acquire a second cell line later in life.

Bone marrow transplants are the clearest example. Bone marrow makes blood cells, so after a successful transplant the recipient's blood can become entirely donor type. Other tissues may not change. A 2014 study in Biomedical Reports followed one patient 13 years after a bone marrow transplant. His blood was 100% donor DNA, and his cheek swabs were about 58% donor DNA. His hair follicles and sperm were 100% his own original DNA.

This means a transplant recipient's blood can carry a different person's genetic profile while his sperm still carries his own. Any children would inherit his original DNA, not the donor's. The study looked at only one patient, though, and its authors say larger samples are needed to confirm the pattern. It should be read as a detailed example, not a general rule.

Microchimerism from pregnancy is the other route. During pregnancy, cells from the fetus can circulate in the mother's body. These cells are few compared with the rest of the body, which is why the condition is called *micro*chimerism. Its cause is well established. Questions about how long these cells stay and whether they affect the mother's health are still under active research. Popular claims about long-term health effects go beyond what can be stated with confidence.

Why it matters for DNA tests

DNA testing is used in three high-stakes areas: paternity and maternity, forensics, and medical matching for transplants. Chimerism can complicate all three. The Fairchild case raised concern that DNA evidence is not infallible for proving identity and parentage. Legal scholar David Kaye argued that such cases are exceptions and should not significantly change how DNA evidence is used. Both views can be true. Chimeras are rare, but when a result makes no biological sense, chimerism is worth considering.

Which sample is tested matters. For transplant recipients, blood and cheek swabs can show donor DNA. The 2014 study suggests hair follicles and sperm as references for a recipient's original genotype. For people born as chimeras, the sample that holds the answer may be one that standard tests never collect.

That is why chimerism is probably under-detected. Most chimeras are healthy, most tests use only one tissue, and most tests are never cross-checked against a second. The known cases came to light only because a result was impossible.

Sources (4)

• The Case of Lydia Fairchild and Her Chimerism (2002) – ASU Embryo Project Encyclopedia
• An Impossible Crime, Unless You Know About Chimeras – McGill Office for Science and Society
• Frontiers in Genetics, 2022 – review of human chimerism
• Biomedical Reports, 2014 – DNA chimerism after bone marrow transplantation

Photo by mirerek8 on Pixabay.