Tetragametic chimerism is a form of congenital chimerism. This condition occurs through the fertilization of two separate ova by two sperm, followed by the fusion 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 nonidentical twins (although a similar merging presumably occurs with identical twins, but as their DNA is almost identical, the presence would not be immediately detectable in a very early (zygote or blastocyst) phase. As such, they can be male, female, or hermaphroditic.
As the organism develops, it can come to possess organs that have different sets of chromosomes. 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, though more recent evidence suggests that it is not as rare as previously believed.
This is particularly true for the marmoset. Recent research shows most marmosets are chimeras, sharing DNA with their fraternal twins.
Most 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 downwards from the shoulders down to the lower back; this is one expression of pigment unevenness called Blaschko's lines.
Affected persons may be 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 blastocysts are of opposite sex, genitals of both sexes may be formed, either ovary and testis, or combined ovotestes, in one rare form of intersexuality, a condition previously known as true hermaphroditism.
Note that the frequency of this condition does not indicate the true prevalence of chimerism. Most chimeras composed of both male and female cells probably do not have an intersex condition, as might be expected if the two cell populations were evenly blended throughout the body. Often, most or all of the cells of a single cell type will be composed of a single cell line, i.e. The blood may be composed prominently of one cell line, and the internal organs of the other cell line. Genitalia produce the hormones responsible for other sex characteristics. If the sex organs are homogeneous, the individual will not be expected to exhibit any intersex traits.
Natural chimeras are almost never detected unless they exhibit abnormalities such as male/female or hermaphrodite characteristics or uneven skin pigmentation. The most noticeable are some male tortoiseshell cats or animals with ambiguous sex organs.
The existence of chimerism is problematic for DNA testing, a fact with implications for family and criminal law. The Lydia Fairchild case, for example, was brought to court after DNA testing apparently showed that her children could not be hers. Fraud charges were filed against her and her custody of her children was challenged. 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, 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 she wasn't their mother.
The tetragametic state has important implications for organ or stem-cell transplantation. Chimeras typically have immunologic tolerance to both cell lines.
Tetragametic chimerism, as it affects homosexuality and transgender identity, is properly termed macro-chimerism since, in theory, it can be hexagametic or more, if more than two embryos merge. But since male cells outgrow female cells in this condition, the majority of male/female chimeras should be phenotypically male. Since the majority of any organ tends to be made from one embryo or the other, while a mixed-sex brain could occur in any proportion, generally the brain would be primarily male or female.
Read more about this topic: Chimera (genetics)