UW scientists have discovered "semi-identical" twins — twins that share identical DNA with their mother, but contain DNA from two different sperm, according to the April issue of the Journal of Human Genetics.

Identical twinning occurs when one egg, fertilized by one sperm, splits early in embryonic development, said Vivienne Souter, a resident in obstetrics and gynecology at Banner Good Samaritan Hospital in Phoenix, Ariz. and a lead author on the paper.

"Non-identical twins arise when two eggs are fertilized by two sperm," Souter said. "The two twins are like siblings, in terms of their genetic similarity."

The phenomenon of semi-identical twinning was only discovered when one of the twins was referred to a "gender team" because of differences in her genitalia, said Melissa Parisi, assistant professor of pediatrics in the division of medical genetics.

"One of the twins had an enlarged clitoris," Parisi said. "When we evaluated her chromosomes, we found she had a mixture of XX and XY containing cells."

Females typically have two X sex-determining chromosomes in all their cells, while males have one X and one Y.

Further genetic tests revealed that her twin brother also contained a mixture of two different types of sex chromosomes in his cells.

Two possible events could have led to the formation of semi-identical twins. In the first possibility, a single egg separated into two identical eggs, and each of those eggs was fertilized by a different sperm cell. One sperm cell would contain an X sex chromosome; the other would contain a Y sex chromosome, Parisi said.

"Then, essentially, you had two embryos that were developing side by side and got mixed in together, prior to separating to form the twins," Parisi said. "By chance, the twin that looked like a typical male ended up with more of the Y chromosome containing cells in critical places like the gonads."

Traditional wisdom holds that an egg cannot divide until after fertilization, Souter said.

"But from in vitro fertilization labs, there are reports of eggs dividing prior to fertilization," Souter said. "They're not thought to be viable, but we really just don't know."

In another possible scenario, which some scientists believe is more likely, two separate sperm cells simultaneously fertilized one egg, Parisi said.

"Usually once the head of the sperm has pushed through into the egg, a barrier comes up to prevent any further fertilization," Souter said. "But we do know that relatively frequently, two sperm will fertilize an egg. Most times it's not a viable pregnancy, because it's got three sets of chromosomes rather than the usual two."

But sometimes abnormalities in an embryo's initial number of chromosomes can be corrected, Souter said.

"Some speculate that very early in development, maybe at the two-cell stage, one cell shed the chromosomes from one sperm, and the other cell shed the chromosomes from the other sperm, and then you continue to have these two embryos dividing, mixing and then separating into twins later on," Parisi said.

The two twins don't have equal portions of X and Y sex chromosomes in all of their cells, according to the paper. One twin was anatomically male, while the other twin had ovotestes, or a gonad that is a mixture of both ovarian and testicular tissue. Internally, this twin had both a hemi-uterus and male internal ducts, Parisi said. The first twin is being raised male. The second twin is being raised female.

"They're both doing very well, they're healthy, growing normally and developing normally," Parisi said. "They seem to be developing the gender identity you would expect for their gender assignment."

Since the phenomenon of semi-identical twinning is so rare, further research in humans will prove difficult, she said. Animal models may not provide much help either, Souter said.

"Twinning is different in different animals, so I'm not sure that experiments performed in an animal model will be representative of what happens in humans," Souter said. "I do think we have a very interesting opportunity to look at this more in depth through in vitro fertilization. We can look more carefully at these embryos in the first five days after fertilization to find anything that may give us a clue to what's happening."

Reach reporter Tia Ghose at news@thedaily.washington.edu.