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Understanding Twins

Identical Dilemmas: What Causes Identical Twinning?

New research identifies identical twins from their chromosomes.

Key points

  • We do not fully know what causes identical twinning.
  • New research brings us closer to knowing what causes a fertilized egg to divide.
  • Newly uncovered evidence indicates that some deceased historical figures were part of identical twin pairs.

Events leading to identical twinning seem to be beyond our current understanding, even though identical twins are such sought after participants in psychological studies. We do know that identical twins occur in about .3-.4% of births worldwide. There are several theories for why this happens: (1) Cell repulsion hypothesis: Developmental differences between adjoining cells might cause repulsion, leading the fertilized egg or zygote to divide; (2) Co-dominant axes: Two embryonic axes form and develop, possibly causing the fertilized egg to split; and (3) Lowered embryonic calcium levels: Reduced calcium levels weaken bonds between cells, causing the division. Other theories of identical twinning have also been proposed.

Genomic Imprinting

There is an intriguing association between identical twinning and disorders associated with genomic imprinting. Genomic imprinting occurs when a gene passed from the father leads to one condition in a child, while that same gene passed from the mother leads to a different condition in the child. For example, the same gene on chromosome 15 transmitted by the mother leads to Angelman syndrome, while the same gene transmitted by the father leads to Prader-Willi syndrome. Individuals with Angelman syndrome have unusual facial structure, inappropriate bouts of laughter and an awkward gait. Individuals with Prader-Willi syndrome have weak muscle tone and developmental delays.

In a related occurrence, there are more identical twins who differ in Beckwith-Wiedemann Syndrome (BWS), than those who are both affected. BWS is a condition in which affected individuals grow taller than their peers, a process that usual ends when they are eight years old. The gene underlying this condition can be transmitted by the mother or the father. However, about 20% of the affected children receive a particular gene from their father that is active. However, if children receive the same gene from their mother, the risk of being affected is 50%. Researchers think it is possible that that an imprinting defect may have happened at a critical moment before the fertilized egg implants in the uterus, and that the defect caused it to divide, resulting in identical twins.

Identical Twins: More Than Just One Kind

Twinning expert Judith Hall has recognized three types of identical twinning in humans: (1) Spontaneous: This type of twinning seems to occur with the same frequency worldwide, i.e., 1/250 births. She thinks it may come from overripe eggs that may not function normally, leading to unusual development; (2) Familial: This type of twinning may involve an atypical protein (of maternal origin), causing problems with cell connections (of maternal or paternal origin) and cells coming apart; and (3) Assisted Reproduction-Related: This type of twinning has been explained by manipulation of the zona pellucida (a structure that surrounds the embryo before implantation), hardened zona due to freezing or culturing, a thin zona or some unspecified deficit.

Clomiphene citrate (clomid), a fertility drug, has also been associated with identical twinning. A number of years ago, researchers linked clomid to polar body twinning, sometimes called the “third” twin type. There are a variety of possible polar body twins, but basically this can happen when the mature egg and one of the three polar bodies produced during the egg’s maturation process become fertilized. In such cases, twins vary as to their genetic relatedness. They could, for example, share their mother’s genes, but half their father’s genes, on average.

An Exciting Breakthrough

The most recent insights into what can be thought of as the “mysteries “of monozygosity (i.e., identical or monozygotic twinning) were reported in a 2021 article by von Dongen at the Vrije University in Amsterdam, the Netherlands and numerous international colleagues. They found that identical twins have certain markers near certain chromosomal regions. Give this finding, they demonstrated that they could identify identical twins, using different twin samples and different biological materials, with high probabilities (77 to 80%).

They believe that events related to cell adhesion accounts for why the fertilized egg sometimes divides. Of course, further work needs to be done in this area to confirm this interpretation. I think this is one of the most exciting discoveries concerning the origins of identical twinning to come along in a while,

\Scientists are fascinated by problems and questions surrounding twins that remain unsolved. Therefore, it is not surprising that this research generated intense interest worldwide. The work has many applications. For example, it can help solve cases involving reared-apart identical twins, switched-at-birth identical twins, kidnapped twins and individuals who believe that their psychological problems come from the loss of an alleged co-twin during mothers’ pregnancy.

Newly uncovered evidence that deceased historical figures were part of an identical twin pair might also prompt investigation of their remains. There is, in fact, an unpublished book by Sarah Madry offering evidence that Louis XIV had an identical twin brother. Other circumstances in which identifying identical twins may prove useful will most certainly arise. It will be exciting to learn what they are!

References

von Dongen, J., Gordon, S. D., McRae, A. F., Odintsova, V. V., Mbarek, H., Breeze, C. E., ... & Boomsma, D. I. (2021). Identical twins carry a persistent epigenetic signature of early genome programming. Nature communications, 12(1), 1-14.

Hall, J. G. (2021). The mystery of monozygotic twinning I: What can Amyoplasia tell us about monozygotic twinning and the possible role of twin–twin transfusion?. American Journal of Medical Genetics Part A, 185(6), 1816-1821.

Hall, J. G. (2021). The mystery of monozygotic twinning II: What can monozygotic twinning tell us about Amyoplasia from a review of the various mechanisms and types of monozygotic twinning?. American Journal of Medical Genetics Part A, 185(6), 1822-1835.

Blickstein, I., & Keith, L. G. (2007). On the possible cause of monozygotic twinning: lessons from the 9-banded armadillo and from assisted reproduction. Twin Research and Human Genetics, 10(2), 394-399.

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