Microchimerism and its importance

Every criminal case looks for biological evidence as the crux of the matter or the most crucial evidence. In the majority of cases, it serves as proof of conviction; the deepest factor being the DNA profile. DNA evidence has been used in courtrooms for over thirty years now. Since an individual’s DNA profiles, also known as genetic profiles, are unique to themselves, they provide a strong and unmistakable alibi in any case. But is this true under all circumstances?

As we delve deeper into the power of forensic science and its unique nature of distinguishing right from wrong, let’s read about microchimerism, its characteristics, and how, if any, can they play a role in forensic science.

In many cases, there is the presence of a set of genetically distinct cells in an individual’s body. Although less mentioned, its occurrence is quite frequent. And the phenomenon is qualified as microchimerism.

The word microchimerism is derived from the word “chimera,” which according to Greek mythology is a monstrous figure whose body consists of parts of three animals: a lion, a snake, and a goat. In human genetics, it is defined as the presence of two genetically distinct cell populations within the same individual. This results in the presence of a minor amount of genetically different DNA, also called “foreign DNA”, in the body of the same individual. These distinct cells will always exist as a tiny population, compared to the host’s own cells. Hence the name of micro-chimerism.

Types of microchimerism

Based on the mode of occurrence, microchimerism can be classified into 2 main types:

1) Natural: Those that occur by natural means and without human intervention.

2) Artificial: Occurring as a sequel to an activity performed on the human body.

Natural microchimerism and its causes:

  1. Fetal microchimerism

It is the most widespread type of microchimerism (Mc). During pregnancy, a small population of fetal cells migrates through the mother’s body and becomes part of the maternal organs. These cells persist in maternal blood for up to 30 days after childbirth. However, in some cases, fetal cells are also seen in the body after 30 decades postpartum.

  1. Maternal microchimerism

Although less common than fetal microchimerism, maternal leukocytes have been observed in the skin, spleen, thymus, and liver during the early fetal and neonatal life of the baby. It has been found that normal childbirth results in increased transport of maternal cells to the fetus, while cesarean section results in increased transfer of fetal cells to the mother.

Artificial microchimerism:

  1. Blood transfusion

It is medically called transfusion associated microchimerism (TA-MC). Leukocytes persist for up to 30 days in the bloodstream of the patient who has undergone a transfusion.

  1. Organ transplant

The transplanted cells often migrate out of the transplanted graft into the peripheral organs of the host. This includes the skin, lymph nodes, and peripheral blood.

  1. Bone marrow transplant (hematopoietic stem cell transplant)

This causes a more persistent type of microchimerism in an individual. Since red blood cells are produced in the bone marrow, a bone marrow transplant will result in the newly produced red blood cells carrying the donor’s DNA. Thus, a foreign DNA, that is to say the DNA of the donor, would circulate in the blood of the patient. At the same time, the patient’s other organs will carry their own original DNA. This makes the patient a real pipe dream.

How long does foreign DNA persist in a host’s body?

In blood transfusions, the time that foreign DNA persists in the body depends on the amount of blood received during the transfusion. Smaller-scale transfusions will remove foreign cells in 7-10 days. In large-scale transfusions, even persistence of foreign DNA is observed for up to a year and a half.

In organ transplant cases, foreign DNA has been around for years. This is true, especially in kidney transplant cases. However, the cell population is too small and limited to certain locations only.

What is more relevant in terms of criminal investigation are the cases of bone marrow transplant, because it gives rise to a permanent chimera. In some cases, the donor’s cells can infiltrate almost any part of the body except the hairline.

Microchimerism in Forensic Science: Why Should We Give It Importance?

In recent years, the number of stem cell or bone marrow transplants has increased, which makes it important to consider chimerism from a forensic perspective. Since microchimerism is the harboring of a small population of foreign cells within an individual, it can often lead to a confusing genetic profile of the host.

The appearance of two sets of DNA profiles of the same person can put forensic scientists, crime scene investigators and DNA profilers in a questionable and troubling situation. Such cases have occurred in which offenders have undergone transfusions or transplants.

Another challenge encountered is that the donor’s DNA may be present only in certain places or specimens of the body. It may not even be uniform for all patients who have had a transplant. For example, patients who have had a bone marrow transplant may show donor DNA in their bloodstream and sperm, while only their own DNA in cheek cells and other tissues. This means that the biological evidence of a certain bodily specimen may not be reliable for individualization and paternity testing.

Moreover, since cases of chimeric incidents are quite rare and evidence contamination events are more numerous, scientists could easily be misled by doubts of cross-contamination or DNA mixing.

This is especially true and difficult in cases of sex determination, where an individual is a chimera carrying cells and DNA of the opposite sex. In other words, when the patient has received a transplant from an individual of the opposite sex. Apart from transplant cases, similar situations can even occur in twins of opposite sexes. This could be due to the transfer of blood between the two babies during the gestation period. Another example is that of women bearing male children and therefore carrying DNA of the opposite sex in their bodies.

All these cases can lead to chimerism. And samples of these can produce erroneous results in DNA-based gender analysis. Since cell populations of both sexes are present, the use of male or female-specific STR markers will produce erroneous electropherogram readings, thus causing more confusion.

One of the oldest and most discussed cases of chimerism is that of a sexual offense case in Alaska in 2005. A semen sample was found at the scene of the crime and the police had its prime suspect. During DNA profiling of the suspect’s blood sample, a match was obtained. However, this surprised investigators as the match involved a person who was in prison when the assault took place. Upon further investigation, it was discovered that the suspect had undergone a stem cell transplant, the donor of which was his brother, the person in prison.

How to overcome such errors in forensic DNA analysis?

If multiple samples of a chimeric individual are obtained at the crime scene, the analyst will have no idea that these samples are from the same person. The analyst would naturally conclude that there were two people involved, and the case would build up on false assumptions.

Another way the case can be dropped is if a blood or semen sample is obtained at the crime scene and a mouth swab is taken from the suspect, which could be a pipe dream. Now, even if the suspect is the real offender, the samples may not match exactly.

One way to solve such problems would be to strictly test “as with as”. A blood sample could be tested against blood, semen against semen, and saliva against saliva. The results of these tests would never be different or wrong.

In circumstances giving rise to erroneous and confused profiles, the analysis could proceed to a hypothesis of chimerism. The fact that chimeras exist is both instructive and stimulating to some extent. In the future of DNA analysis for criminal investigations, knowledge of microchimerism and its possible errors may be of great precedence. And as the popular saying goes, “Let a hundred guilty be acquitted, but no innocent should be convicted,” the detection and analysis of microchimerisms can exclude innocent individuals from being suspected of a crime.

THE REFERENCES

  1. Catherine Arcabascio, Chimeras: Double the DNA – Double the Fun for Investigators, Prosecutors and Defense Lawyers (2007) Akron Law Review; 435-464
  2. David H. Kaye (2013), Chimeric Criminals, 14 MINN. JL SCI. & TECHNOLOGY. 1.
  3. E Sanz-Pena et al (2019) Medico-legal implications of the presence of chimerism after hematopoietic stem cell transplantation. International Forensic Science; 109862
  4. J Lee Nelson (2003) Microchimerism in Human Health and Disease. Autoimmunity; 36
    (1): 5-9
  5. Renjith George et al (2013) The impact of chimerism in DNA-based forensic sex determination analysis. Malaysian Journal of Medical Sciences; 20 (1): 76-80
  6. Arthur Liang (2020) Chimerism and how it can skew criminal investigations. the spectator; 110 (8)
  7. Joanna Rutkowska et al (2007) Donor DNA is detected in the recipient’s blood for years after kidney transplantation using sensitive forensic methods. Transplantation annals; 12 (3): 12-4
  8. Sandhya Srivastava et al (2019) Microchimerism: A New Concept. Journal of Oral and Maxillofacial Pathology; 23 (2): 311

AUTHOR

Aiemy Mary Sam

National University of Forensic Sciences

(lot distributed from 2018-2020)


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