Biology concepts – mosaicism, mosaic twins, chimera, anaphase lag, non-disjunction, polar body twins, oogenesis, preimplantation genetic screening
In organisms with chromosomes, this isn’t the normal case. Each individual is made up of many cells, but each cell has exactly the same complement of chromosomes. But not always. Mosaicism in genetics refers to an individual where not every cell has the same chromosomal makeup. Some cells have genetic makeup "A" and some have genetic makeup "B." But it doesn’t have to be limited to two genetically different cell populations, there could be more.
We have talked about mosaics before (this post and this post). They can come from a chromosome loss in an early cell that then divides and becomes a whole population of cells with that different chromosome number. It can also come from an endoreplication event (see this post) where a cell ends up with too many of a certain chromosome. There could be a non-disjunction event as well; this is how Down syndrome or Klinefelter’s syndrome come about.
Anaphase lag is yet another mechanism to create a cell with different chromosome number. In this case, the spindle apparatus (see this post) in a mitotic or meiotic cell division doesn’t connect completely with a chromosome or doesn’t pull it efficiently. As the spindle pulls the chromatid pairs apart and the two daughter cells start to form nuclei, the tardy chromatid is left out.
Now consider what would occur if the early embryo undergoes a mosaic producing event, and then splits into two embryos – mosaic monozygotic (MZ) twins. A mosaic embryo, no matter what mechanism leads to the mosaic could become mosaic twins, as long as the chromosome change in some cell occurs before the split of the embryo into two embryos. Each twin will end up with some cells of one chromosomal profile, and some of the other. Given all that must happen to create them, is it any wonder that mosaic MZ twins are rare?
But there is another way for a mosaic individual, or MZ twins to form as well. Consider the case of two male gamete cells fertilizing the same egg (called polyspermy). When the zygote cell divides, one cell may get some of male gamete #1 chromosomes and some of male gamete #2 chromosomes. Male gametes carry either an X or a Y, so it is conceivable that some cells will be XX and some will be XY. If the embryo split, could you get MZ twins that are one boy and one girl?
Invertebrate animals have a fast and slow block to prevent
more than one male gamete from reaching the egg. The
fast one occurs within 10 seconds. But mammals have a
couple of slow methods only, including a growth in the
thickness of the zona pellucida by the degranulation of
cortical granules. In mammals, all the mechanisms are
slow (about 1.5 hr), so it is possible for more two male
gametes to get in. This is especially true in IVF where
one in ten embryos undergo polyspermy.
Some people might want to call these twins chimera twins, but chimeras come from the fusion of two embryos into one (two complements of mom’s DNA). Mosaics form from one zygote only. For instance, another mosaic twin case formed after an XXY Klinefelter syndrome embryo lost the Y chromosome in some cell(s) (maybe from an anaphase lag). Then the embryo split and you had an XXY male and an XX female.
Can you think of another way to end up with mosaic twins? What would the result be if a mosaic zygote split so that all the cells of one type ended up in one embryo, while the other embryo ended up with all the cells of the second genotype? Would those be mosaic twins? Would they be MZ twins; would they be genetically identical? How could you tell them apart from dizygotic twins? And yes, there would be a way to tell if they were DZ or started out MZ, can you figure it out?
Imagine the case where a zygote splits into MZ twins and then a cell of one embryo (or both embryos) undergoes an endoreplication or anaphase lag. Now one (or both) embryo is/are mosaic, but they’re different from one another. Would they still be considered mosaic twins?
As was the case with MZ twins in general, the incidence of mosaic twins may be increasing because of assisted reproductive technologies (ART, see this post). There are several different kinds of ART methodologies, but the one we have talked about most is in vitro fertilization (IVF). Where IVF and mosaic may twins cross paths is in something called preimplantation genetic screening (PGS).
To look at the genetic make up of an oocyte, you can’t analyze the nucleus, it’s just one cell and you destroy the nucleus as you do PGS. You have to use something called a polar body. During oogenesis (formation of the egg by mitosis and meiosis) there is the production of a smaller cell that usually isn’t capable of being fertilized; this is the polar body.
The first round of meiosis of the primary oocyte results in the polar body #1 and the secondary oocyte. In meiosis II, the secondary oocyte divides unequally and produces the ovum and the polar body #2. Each division is unequal in terms of cytoplasm, so the polar bodies are smaller than the oocyte.
Sometimes the first polar body will divide again in meiosis II; therefore, you can get three polar bodies for every egg produced. The first polar body (and any daughters of it) will have a different genetic makeup from the egg, but the second polar body will have the same chromosomes as the oocyte.
In PGS of an oocyte, the first or second polar body is harvested for genetic testing before the embryo is implanted in the uterus (not every follicle will retain each polar body). The goal is to identify genetic diseases that the individual will have, or might be predisposed to. If they find a problem, they don’t use that egg for IVF.
In the case of embryos that have undergone IVF already, they will harvest a single cell of the growing embryo to do PGS analysis on that. If that embryo shows chromosomal anomalies, they won’t deliver it to the uterus.
non-disjunction syndromes like Down Syndrome or Klinefelter’s. In embryos PGS can also be used to identify individuals that have acquired two copies of a recessive gene that will guarantee a genetic disease. This is especially sad in cases where the disease doesn’t manifest until the victim has already had children and passed on a possible death sentence – something like Huntington’s disease (see this post) or fatal familial insomnia (see this post).
Unfortunately, most studies indicate that PGS of the oocyte isn’t very helpful in predicting that the embryo will be OK; too many things can go wrong after PGS is done. In one case, two PGS-approved embryos were implanted, but they ended up with triplets. Two babies were mosaic MZ twins and one of them had Down Syndrome.
There is also the suggestion that some oocytes harvested from ovaries for ART are conjoined, made within one follicle. This may increase the chances of mosaicism from fusion. And several instances suggest that PGS can induce twinning, since pulling the cell from the embryo is a lot like induced hatching – and we saw that messing with the zona pellucida is associated with increased MZ twinning.
random assortment in meiosis I, so these might be considered dizygotic twins if the polar body and the oocyte were both fertilized.
But if the second polar body and the oocyte were both fertilized, each embryo would have the same maternal DNA but different paternal chromosomes. Would they be MZ twins? Dizygotic twins? The theoretical names are polar body twins or ½ twins, but science hasn’t proven it can happen yet.
One case of half or semi-identical twins is known, the 2007 case of sex discordant MZ twins with hermaphroditism we talked about above. But since they are mosaics, we know they didn’t come from two separate fertilizations of a polar body and an oocyte. The search continues.
Next week – given the nine types of MZ twins we have talked about, wanna bet that there’s more than one type of dizygotic twins?
For more information or classroom activities, see:
Mosaic twins –
Oogenesis/polar bodies –
Be careful, much of the information on PGS/PGD is from companies that do it for money.