Diverse mammals, including humans, have been found to carry distinct genomes in their cells. What does such genetic chimerism mean for health and disease?
In 1976, researchers from the Lister Institute of Preventive Medicine in London published the puzzling case of a woman who had two different blood types: 93 percent of her red cells were type O, while the remaining 7 percent were type A1, the most common type A subgroup.1 A few years later, Winifred Watkins of the MRC Clinical Research Centre and colleagues came across another blood donor with two distinct red blood cell types, and further investigation led to an even more astonishing finding: a phenotypically normal man, with presumably XY cells in his testes and most of his body, was found to carry XX cells in his skin and other tissues.2
These case studies heralded a new appreciation for the phenomenon of genetic chimerism—when an individual carries two or more genetically distinct cell lines in different parts of her body. Until the advent of techniques for blood typing and karyotyping cells, genetic chimeras where thought to be very rare. They only came to light when the phenotypes associated with the two distinct genomes were so discordant that the resulting individual was clearly exceptional, with patches of distinct skin coloration throughout the body, for example, or hermaphroditic genitals. In reality, genetic chimeras may be quite common, disguised in perfectly normal bodies harboring genetically distinct cell lineages.
While most fictional works portray chimeras as an amalgam of two individuals, the truth is that the individuality of the distinct cell lines is lost as the two combine.
In all likelihood, most chimeras are not even aware of their condition. Boston resident Karen Keegan, for example, would have never discovered her mixed genetic makeup if in 1998, at age 52, she hadn’t needed a kidney transplant. When doctors tested the human leukocyte antigen (HLA) type of her three children to see if any of them could donate a kidney, they were surprised to find that two of the children could not have been hers at all: while all three carried one HLA copy that matched their father’s, only one child carried a second copy that matched Karen’s. Of course, having given birth to these children, she knew they were hers. Sure enough, while Karen had one cell line only in her blood, the doctors eventually found the “missing” HLA type in a second cell line in her skin, hair, bladder, mouth mucosa, and thyroid.3