Chimerism in humans

The simultaneous presence of cells of different genotypes in the body is chimerism. In humans, it has several types and causes of occurrence, let's consider this in more detail.

In Greek mythology, the chimera is a monster with a goat's body, a lion's head and neck, and a snake's tail. To date, there are about 100 known cases of human chimerism. It is not related to mythology and is based on a specific mutation of genes during conception and embryo development. The pathological condition has several types and forms, which differ in the causes of occurrence.

Biological chimeras can occur when two different races interbreed. Very often this manifests itself as a distribution of different pigmentation on the body. If a complete fusion occurs, this indicates a blood pathology, when the child has two DNA strands. Or twins who grew up in the same womb have tolerance to each other's blood type. A similar defect occurs during organ transplantation and even blood transfusion.

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Causes of chimerism in humans

From a genetic point of view, mutations occur due to the presence of two or more cellular strands in a person, developing from different zygotes. The causes of chimerism are varied, most often it is the mixing of blood. This pathology provokes the appearance of the karyotype 46,XX/46,XY. The defect can be associated with the mixing of cells of a living and deceased twin in the mother's womb or the merging of two zygotes into one embryo.

The main causes of chimerism in humans:

• Tetragametic - two eggs merge into one, but each of them is fertilized by different sperm. This happens when, in the early stages of formation, one of the embryos absorbs the other. Because of this, the organs and cells of one organism have a different set of chromosomes.
• Microchimerism – fetal cells penetrate the mother’s bloodstream and take root in its tissues. There are known cases when the immune cells of the embryo cured the pregnant woman of serious diseases and increased resistance to oncological pathologies. This process also works in reverse, that is, maternal cells are integrated into the embryo through the placental barrier. The main danger of the disorder is that the baby can acquire maternal diseases while still in the womb.
• Twinning is a fusion of blood vessels. Heterozygous twin embryos pass parts of their cells to each other. This results in the child having two strands of DNA.
• Post-transplantation – occurs due to blood transfusion or organ transplantation. The body’s own cells coexist simultaneously with the donor’s cells. In some cases, the donor’s cells are completely integrated into the transplanted organism.
• Bone marrow transplantation – the procedure itself is aimed at genetic transformation of the patient’s body. Using radiation and drugs, the patient’s bone marrow is killed. Donor cells are introduced in its place. If donor chimerism is detected according to the test results, the transplant has taken root.

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Pathogenesis

The mechanism of chimerism development depends on the factors that provoked it. Pathogenesis is classified into the following types:

1. Transplantation (iatrogenic) chimeras
2. Primary chimerism

• Embryonic
• Uncertain

3. Secondary mutations

• Feto-fetal chimeras ("fetus - fetus")
• Mother-fetus mutations
• Chimeras of the "fetus - mother" type

Scientists have managed to diagnose a tetragametic disorder, i.e. the fusion of two eggs fertilized by different spermatozoa. The mechanism of development of this condition indicates the presence of two DNA strands in one (surviving) embryo. The pathogenesis of microchimerism indicates the penetration of the baby's cells into the mother's hematopoietic system or the mother's cells into the fetus's body.

Another variant of defect development is the fusion of blood vessels of heterozygous twins who pass on their genetic data to each other. Post-transplantation occurs during transplantation of bone marrow, hematopoietic organs and during blood transfusion. There are also known cases of laboratory mutations (experiments were conducted on animals and plants) according to the chimerization mechanism developed by scientists.

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Symptoms of chimerism in humans

In order to determine whether a person is a chimera, it is necessary to conduct a comprehensive genetic examination. In most cases, there are no obvious symptoms of a pathological condition. Of course, if the mutation has no external signs.

Chimerism occurs during intrauterine development. It occurs when two fertilized eggs merge, one of which absorbs the other, as well as when the genetic information of the embryo and mother mixes, or as a complication of transfusion procedures.

External symptoms of chimerism in humans appear when different races interbreed. This looks like different eye colors in a child or mosaic skin coloring. But in most cases, symptoms are detected by a comprehensive blood test, which indicates the presence of two DNA lines.

Texas Kid

One of the most sensational cases of chimerism known to medicine is the story of an interracial mutation. The Texas baby - that's what this incident was called. The right half of the baby was a mulatto girl, and the left half was a black boy. This is an example of true hermaphroditism with genetically developed primary and secondary sexual characteristics of both sexes in one body. The chimera underwent an operation, giving him the male sex, getting rid of female external characteristics. Of course, genetically, the child remained bisexual with two strands of DNA.

Another terrifying story of chimerism tells of an 11-year-old Chinese girl. A twin brother, absorbed by her, develops from her back. Such mutations occur during intrauterine development, when two zygotes (future twins) merge into one organism. That is, in fact, two people with their own set of genes end up in one body.

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First signs

The presence of two DNA strands in one person is the first sign of chimerism. In most cases, the mutation does not manifest itself with external symptoms. It is possible to establish that a person is a chimera only through genetic testing.

Let's look at some cases of chimerism:

• A Boston teacher needed a kidney transplant. Her three children agreed to be donors, but genetic testing showed that two of them were not their mother's biological children. Further testing revealed that the teacher had a twin sister who had fused with the surviving fetus during embryonic development. That is, the teacher was a chimera, since she had two different sets of genes that did not interfere with each other.
• Another case of chimerism detection also occurred during transplantation. According to the results of the tests, the woman's biological children were not genetically her children. They were related only to their grandmother. Therefore, an analysis of the hair, which contained different genetic material, was carried out and confirmed the family ties.

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Forms

To determine what caused the mutation, the doctor collects anamnesis and conducts a variety of diagnostic genetic tests.

Genetic chimerism

In early pregnancy, that is, during the formation of the embryo, a number of mutations can occur. Genetic chimerism occurs when a pair of fertilized eggs fuse into one. Each zygote contains a strand of parental DNA, that is, its own genetic profile. During the union, the cells retain their individual genetic makeup. That is, the resulting embryo is a combination of both. In most cases, people with such mutations have an immune system that is tolerant of all genetic populations in the body.

In essence, such a human mutation is its own twin and is rare. To determine it, a comprehensive genetic examination is carried out. Both parents and the child undergo DNA analysis. Very often, such studies are necessary to establish a biological connection between children and parents, since the child has a different genetic profile.

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Tetragametic chimerism

Medicine knows of cases when, during tests, parents and children have no genetic similarity, that is, biologically they are not related. Tetragametic chimerism occurs when two twins unite into one during embryonic development. One child dies, and the survivor carries his and her DNA.

Such cases of chimerism can be identified by several signs:

• Hermaphroditism
• Red blood cell population
• Mosaic skin coloration
• Different eye colors

Scientists have described a case where, during conception, the child's genetic information was transferred not from the father, but from his twin brother who died and was absorbed in the womb. That is, from a genetic point of view, the parent is the deceased twin brother. When studying this case, it was found that the genetic code of the child and his father coincides by 10%.

Biological chimerism

One of the mysterious phenomena known to medicine is the combination of several genomes in one body. Biological chimerism occurs in humans, animals and plants. If we consider this mutation in humans, it occurs in the following cases:

• The fusion of two fertilized eggs into one during embryonic development.
• Organ transplant, bone marrow transplant, blood transfusion.
• Incest of different races.

Full fusion is possible when two fetuses growing in the same womb use the same placenta and have tolerance to each other's blood. That is, if necessary, they can be given a transfusion of each other's blood, since the rejection reaction is suppressed at the genetic level. Externally, a biological mutation manifests itself as different-colored irises in one person or a combination of several skin colors (usually have a mosaic arrangement).

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Blood chimerism

Another amazing phenomenon in medicine is two blood groups in one person. Blood chimerism occurs due to a genetic mutation during intrauterine development. In nature, there are such blood groups: O (I), A (II), B (III) and AB (IV).

• Blood type A carries antigen (prompts the body to produce antibodies) A and antibodies B.
• Blood type B carries the B antigen and the A antibody.
• Group AB contains both types of antigens but does not have antibodies.
• Group A has both types of antibodies but no antigens.

Based on this, group A is compatible with A and O, B with B and O. Unique recipients are those with AB, since their biological fluid is compatible with all existing groups. Group O acts as a universal donor, but it is compatible only with the same group O.

Based on the anatomy course, it is known that a living organism can have only one of them. Since immune cells do not accept foreign blood, causing a rejection reaction during transfusion. An exception to this rule are blood chimeras. Such people have two different types of blood and tissues that produce blood cells of both types. Such pathology occurs both among people and animals. All known chimeras are twins. Blood is divided between two embryos, they exchange tissues that produce blood, and the rejection reaction is suppressed.

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Incomplete red cell chimerism

There are natural and artificial factors that provoke the appearance of incomplete erythrocyte chimerism:

• In dizygotic twins, natural mutations occur due to the exchange of hematopoietic cells through vascular anastomoses.
• Artificial chimerism occurs during allogeneic bone marrow transplantation and after blood transfusion. This occurs due to the elimination of donor red blood cells and the return to the original blood group. During organ or bone marrow transplantation, the patient's own red blood cells are replaced by donor ones.

Incomplete chimerism is characterized by the presence of donor and autologous red blood cells in the recipient. This type is a transient circulation of donor red blood cells that have begun to repopulate or are passively transfused with bone marrow.

This pathological condition is alarming. It is associated with unspecified physical changes in the recipient's body. In addition, chimerism can cause psychological problems. Since not all patients are ready to accept their altered anatomy and physiology.

Post-transfusion chimerism

Transfusiology is a science of managing the body through targeted impact on the morphological composition of blood by transfusion. Post-transfusion chimerism occurs when two different blood groups are mixed, when donor cells completely replace or coexist with the recipient's genetic code. This pathology can be called a complication of transfusion or transplantation.

The following transfusion agents are distinguished:

• Blood and its components (erythrocytes, leukocytes, platelets, plasma).
• Blood substitutes are medicinal solutions used in cases of blood dysfunction, to normalize or replace it.
• Bone marrow and hematopoietic organ transplantation.

Post-transfusion chimerism may occur due to the presence of leukocytes in donor blood. If leukocytes are removed from the biological fluid or red blood cell mass, the risk of post-transfusion chimerism, alloimmunization and other complications is minimal.

Complications and consequences

One of the dangers of chimerism is uncontrolled processes in the human body. The consequences of chimerization may be associated with post-transfusion procedures or pathologies during intrauterine development.

Chimerism also calls into question the validity of DNA tests and many court cases. The genetic disorder causes many problems in establishing paternity. There is also a certain percentage of couples who are infertile due to the mutation.

The presence of two DNA strands in one organism can cause a number of complications. First of all, this is associated with physical pathologies. Science knows of a number of cases where children were born with different eye colors, marble pigmentation or additional limbs from twins absorbed during embryonic development.

Another complication of this mutation is that when organ transplantation is required and a related donor is selected, a genetic mismatch is revealed. This raises many questions and complicates the transplantation process. After transplantation, changes in hair structure, blood type and Rh factor may occur.

There is a known case where a patient suffering from AIDS and lymphoma underwent a bone marrow transplant. The donor was a carrier of a mutation that provided resistance to the virus. After the transplant, the recipient passed it on along with the bone marrow. This led to the patient being completely cured of his diseases.

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Diagnostics of chimerism in humans

As a rule, chimerism is diagnosed using DNA analysis, i.e. a test to determine family ties. The choice of this study is explained by the fact that at the cellular level, the defect is a mixture of two genotypes in one organism.

High-tech molecular methods are used for examination. If chimerism is suspected, the patient will undergo a set of tests, instrumental and mandatory differential diagnostics. The doctor will learn about the family history, that is, the hereditary predisposition to mutations.

Tests

The use of one or another method depends on the availability of information about the possible type of disorder. Tests for suspected chimerism are aimed at genetic testing of blood and DNA. Screening and detection laboratory methods are used, let's consider them:

1. Mutation screening is used when the nature of the mutation is unknown, but family history suggests the presence of a gene rearrangement.

• Analysis of macrorearrangements by DNA blotting.
• Heteroduplex analysis.
• Single-stranded DNA conformation polymorphism analysis.
• Electrophoresis of double-stranded DNA in a denaturant gradient.
• Denaturing high performance liquid chromatography.

2. Chemical detection of unpaired nucleotides - mutation detection is based on denaturing a control sample with normal DNA. The samples are cooled, forming duprexes, some of which will have unpaired bases indicating a mutation.

• RNase protection.
• Screening.
• Mutation detection.

The above-described analyses are used in molecular DNA research for various genetic pathologies, mutations, including chimerism.

Instrumental diagnostics

If chimerism is suspected, the patient will undergo a whole range of different diagnostic procedures. Instrumental diagnostics are necessary to study the condition and structure of internal organs and other structures of the body. Since it is known that with chimerism, the hematopoietic organs (bone marrow, thymus, spleen, endocrine glands, etc.) produce blood with different DNA alleles.

The patient undergoes screening tests, CT, MRI, ultrasound diagnostics and other procedures. In most cases, detailed instrumental diagnostics are necessary for organ transplantation or blood transfusion, when the patient wants to act as a donor or recipient.

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Differential diagnosis

A chimera is a combined organism that originated from more than one zygote. There are a number of pathological cases that have similar origins. Differential diagnostics is aimed at identifying them.

Let's consider who looks like a chimera but is not one:

1. Hybrids

• Genetic.
• Somatic.

2. Mosaics

• Chromosomal.
• Genetic.
• Epigenetic.

3. Gynandromorphs
4. Teratogenic effects of varying severity caused by disruption of genes responsible for developmental processes.
5. Natural occurrences that may be accompanied by mutations

• Freemartins.
• False hermaphroditism.
• Severe congenital anomalies.
• True hermaphroditism.
• Ovotestis.
• Anomalous twinning.

During the differentiation process, all the above-described genetic mutations are considered, and the DNA of the patient and his relatives is examined.

Treatment of chimerism in humans

One of the tools of biotechnology is genetic engineering. This science is a complex of methods aimed at isolating genes from an organism, performing various manipulations with them, introducing them into different organisms, obtaining recombinant DNA and RNA. Treatment of chimerism, its study and creation, is possible with the help of such genetic technologies.

With the help of genetic engineering, doctors control the process of chimerization. This is possible during bone marrow transplantation, other organs or blood transfusions. This is a kind of creation of radiation chimerism in clinical conditions.

As for the treatment of chimeras with external manifestations, such as in the case of the Texas child, with mosaic skin coloring, different eye colors, or with additional limbs from twins absorbed in the womb, the therapy is aimed at correcting external defects. Treatment is carried out in the first years of the patient's life. This allows achieving good results and minimizing disruptions to the socialization process. In this case, genetic changes, i.e. the removal of one of the DNA strands, are not used.

Prevention

The study of genetic anomalies in the human body is aimed at preventing various mutations. Prevention of chimerism caused by natural factors is impossible. Since today there are no accessible and safe methods that allow tracking the process of embryo development in the mother's womb.

But it is possible to prevent chimerism caused by post-transfusion procedures (bone marrow transplant, organ transplant, blood transfusion). Genetic engineering is used by couples who have a high risk of having children with genetic pathologies. In this case, to prevent mutations, additional cells are implanted into the embryo, normalizing the chromosome set of the future child.

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Forecast

Chimerism in humans is a different genetic code in one organism. The prognosis of such a mutation depends on the cause that caused it. If these are blood chimeras, then throughout life a person may never know that he has two sets of DNA. This is due to the fact that special studies are needed to detect the anomaly and in most cases this type of disorder has no external signs. If chimerization is associated with artificial methods, then its prognosis is difficult to determine. Thus, during a bone marrow transplant, the patient's blood type, Rh factor and some features of appearance (eye color, hair) that the donor had may change.