Chimerism in humans

Simultaneous presence of cells of different genotypes in the body is chimerism. In humans, it has several types and causes of appearance, we will consider it in more detail.

In Greek mythology, the chimera is represented by a monster with a goat's body, a head and a neck of a lion and a snake's tail. To date, about 100 cases of human chimerism are known. It has nothing to do with mythology and is based on a specific mutation of genes in the process of embryo conception and development. The pathological condition has several types and forms, which differ in the causes of the onset.

Biological chimeras can occur when incest of two different races. Very often this manifests itself as the distribution of different pigmentation on the body. If a complete fusion occurs, this indicates a bloody pathology when the child has two strands of DNA. Or twins, who grew up in one womb, have tolerance to each other's blood group. A similar defect occurs when organs are transplanted and even when blood is transfused.

[1], [2], [3]

Causes of the chimerism in humans

From a genetic point of view, mutations arise 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 this is the mixing of blood. This pathology provokes the appearance of karyotype 46, XX / 46, XY. A defect can be associated with mixing cells of living and deceased twins in the mother's womb or by combining two zygotes into one embryo.

The main causes of chimerism in humans:

• Tetragametic - two ovules merge into one, but each of them is fertilized by different spermatozoa. This happens when the first stages of formation of one of the embryos absorbs the second. Because of this, the organs and cells of one organism have a different chromosomal set.
• Microchimerism - Fetal cells penetrate into the maternal circulatory system and take root in its tissues. There are cases when immune cells of an embryo have cured a pregnant woman from serious diseases and increased resistance to oncological pathologies. This process works in the reverse order, that is, the mother cells through the placental barrier are built into the embryo. The main danger of the disorder is that in the womb the baby can acquire maternal illnesses.
• The twin is the fusion of blood vessels. Heterozygous twin embryos transmit each other parts of their cells. This leads to the fact that the child can have two strands of DNA.
• Post-transplantation - occurs due to blood transfusion or organ transplantation. Own cells of the organism co-exist simultaneously with the donor cells. In some cases, donor cells are fully integrated into the transplanted organism.
• Bone marrow transplantation - the procedure itself is aimed at the genetic transformation of the patient's body. With the help of radiation and drugs, the bone marrow of the patient is killed. In its place, donor cells are introduced. If the results of the tests revealed donor chimerism, the transplant took root.

[4], [5]

Pathogenesis

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

1. Transplantation (iatrogenic) chimeras
2. Primary chimerism

• Embryonic
• Uncertain

3. Secondary mutations

• Feto-fetal chimeras ("fruit-fetus")
• Mutations of the "mother-fruit" type
• Chimeras of the type "fruit-mother"

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

Another option for the development of a defect is the fusion of the blood vessels of heterozygous twins, which transmit their genetic data to each other. Post-transplantation occurs when bone marrow transplantation, blood-forming organs and blood transfusion occurs. There are also cases of laboratory mutations (experiments were conducted on animals and plants) according to the developed mechanism of chimerization.

[6], [7], [8], [9]

Symptoms of the chimerism in humans

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

Chimerism occurs in prenatal development. This occurs when two fertilized ovules merge, one of which absorbs the second, and also when the genetic information of the embryo and the mother are mixed or as a complication of transfusion procedures.

External symptoms of chimerism in humans are manifested when incest of different races. It looks like a different eye color in a child or a mosaic skin color. But in most cases, the symptoms are detected with a detailed blood test, which indicates the presence of two DNA lines.

Texas child

One of the most sensational cases of chimerism, known to medicine, is the history of interracial mutation. A Texas child - that's how the incident was nicknamed. The right half of the baby was a mulatto girl, and the left was a Negro boy. This is an example of true hermaphroditism with genetically developed primary and secondary sexual characteristics of both sexes in one body. Chimera performed the operation, giving him the male sex, having rid of the female external signs. Of course, that genetically, the child remained a bisexual with two strands of DNA.

Another horrific story of chimerism tells of an 11-year-old Chinese girl. From the back of the child develops the twin brother it absorbed. Such mutations occur during the intrauterine development, when two zygotes (future twins) merge into one organism. That is, in fact, in one body there are two people with their own set of genes.

[10], [11], [12]

First signs

The presence of two DNA strands in one person is the first signs of chimerism. In most cases, the mutation is not manifested by external symptoms. It is possible to establish that a person is a chimera only through genetic research.

Consider several cases of chimerism:

• The Boston teacher needed a kidney transplant. Three of her children agreed to become donors, but the genetic analysis indicated that two of them are not native to their mother. Further studies established that the teacher had a twin sister who merged with the surviving fetus during embryonic development. That is, the teacher turned out to be a chimera, as in her body there are two different sets of genes that do not interfere with each other.
• Another case of detecting chimerism, also occurred during transplantology. According to the results of the analysis, the woman's native children were not genetically her children. They had a kinship only with the grandmother. Therefore, an analysis of the hair was carried out, which contained different genetic material and confirmed the family ties.

[13], [14], [15], [16], [17], [18], [19]

Forms

In order to determine what caused the mutation, the doctor collects an anamnesis and conducts a lot of diagnostic genetic tests.

Genetic chimerism

In the early stages of pregnancy, that is, during the embryo formation, a number of mutations can occur. Genetic chimerism occurs when a pair of fertilized ovules merge into one. Each of the zygotes contains a strand of parental DNA, that is, its genetic profile. During unification, the cells retain their individual genetic appearance. That is, the resulting embryo is a combination of both. In most cases, people with similar mutations have an immune system that is tolerant of all genetic populations in the body.

At its core, such a human mutation is its own twin and is rare. To determine it, a complex genetic examination is carried out. The analysis of DNA is handed down by both parents and the child. Very often, such studies are necessary to establish a biological connection between children and parents, since the child has a different genetic profile.

[20], [21]

Tetragamet chimerism

Medicine knows cases when, during the delivery of tests, parents and children do not have genetic similarity, that is, they are not biologically related. Tetragametic chimerism occurs when two twins are combined into one during embryonic development. One child dies, and the survivor carries his and his DNA.

Such cases of chimerism can be identified on several grounds:

• Hermaphroditism
• Population of red blood cells
• Mosaic skin coloring
• Different eye color

Scientists described the case when during the conception the genetic information to the child passed not to the father, but from his deceased and absorbed in the womb of his twin brother. That is, from a genetic point of view, the parent is a deceased twin brother. When studying this case, it was found that the genetic code of the child and his father is 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, then it occurs in such cases:

• Fusion of two fertilized eggs into one during embryonic development.
• Transplantation of organs, bone marrow, blood transfusion.
• Incest of different races.

Perhaps a complete fusion, when two fetuses growing in one womb, use one placenta and have a tolerance for each other's blood. That is, if necessary, they can do blood transfusions for each other, since the rejection reaction is suppressed at the genetic level. Externally, the biological mutation manifests itself as a different color in the color of the iris in one person's eyes or a combination of several skin colors (as a rule, have a mosaic arrangement).

[22], [23], [24], [25], [26]

Blood Chimerism

Another amazing phenomenon in medicine is two blood groups in one person. Bloody chimerism arises from a genetic mutation in intrauterine development. In nature, there are blood groups: O (I), A (II), B (III) and AB (IV).

• The blood of group A spreads the antigen (induces the body to produce antibodies) A and antibodies B.
• The blood of group B carries antigen B and antibodies A.
• Group AB contains both types of antigens, but does not have antibodies.
• Group A has both kinds of antibodies, but does not have antigens.

Proceeding from this group A is compatible with A and O, B with B and O. Unique recipients are holders of AB, since their biological fluid is compatible with all available groups. A universal donor is O, but it is compatible only with the same group O.

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

[27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37],

Incomplete erythrocyte chimerism

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

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

For incomplete chimerism is characteristic of the recipient of donor and autologous erythrocytes. This type is a transient circulation of red blood cells of the donor, which began to repopulate or passively transplanted with the bone marrow.

Such a pathological condition raises fears. This is due to unidentified physical changes in the recipient organism. 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 the science of controlling the body through a targeted effect on the morphological composition of blood by transfusion. Post-transfusion chimerism occurs when two different blood groups are mixed, when the donor cells completely replace or coexist with the genetic code of the recipient. This pathology can be called a complication of transfusion or transplantation.

There are such transfusion means:

• Blood and its components (erythrocytes, leukocytes, platelets, plasma).
• Blood substitutes are medicinal solutions used in violation of blood functions, for its normalization or substitution.
• Transplantation of bone marrow and hematopoiesis.

Post-transfusion chimerism may occur due to the presence of leukocytes in the donor blood. If leukocytes are removed from a biological fluid or erythrocyte mass, then the risk of posttransfusion 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 posttransfusion procedures or pathologies during intrauterine development.

In addition, chimerism calls into question the veracity of DNA tests and many court cases. Because of the genetic disorder, many problems arise with the establishment of paternity. There is also a certain percentage of couples that are infertile due to mutation.

The presence of two strands of DNA in one organism can cause a number of complications. First of all, it is connected with physical pathologies. Science knows a number of cases when babies with different eye color, marbled pigmentation or additional limbs were born from the twins absorbed during embryonic development.

Another complication of this mutation is that, if it is necessary to transplant organs and select a related donor, a genetic mismatch is revealed. This raises many questions and complicates the process of transplantation. After a transplant, changes in the hair structure, blood group and Rh factor may occur.

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

[38], [39], [40], [41], [42], [43], [44], [45], [46]

Diagnostics of the chimerism in humans

As a rule, the diagnosis of chimerism is carried out by means of an analysis on DNA, that is, a test for the determination of 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.

For the survey, high-tech molecular methods are used. If there is a suspicion of chimerism, the patient will have a set of tests, instrumental and mandatory differential diagnostics. The doctor learns about a family history, that is, hereditary predisposition to mutations.

Analyzes

The use of this or that method depends on the availability of information on the possible type of disorder. Analyzes with suspicion of chimerism are aimed at genetic research of blood and DNA. Screening and detection laboratory methods are used, consider them:

1. Mutational screening - is used in the case when the nature of the mutation is unknown, but the family history allows presuming the presence of gene rearrangement.

• Analysis of macroblocking by DNA-blotting.
• Heterod duplex analysis.
• Analysis of the polymorphism of the conformation of single-stranded DNA.
• Electrophoresis of double-stranded DNA in a gradient of a denaturant.
• Denaturing high-performance liquid chromatography.

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

• Protection from the pontic.
• Screening.
• Detection of mutations.

The above analyzes are used for molecular DNA studies on various genetic pathologies, mutations, including chimerism.

Instrumental diagnostics

If a suspected chimerism of the patient is waiting for a whole range of different diagnostic procedures. Instrumental diagnosis is necessary for studying the condition and structure of internal organs and other body structures. Since it is known that in the chimerism, the hematopoietic organs (bone marrow, thymus, spleen, endocrine glands and others) produce blood with different alleles of DNA.

The patient is screened, CT, MRI, ultrasound and other procedures. In most cases, detailed instrumental diagnosis is necessary for organ transplantation or blood transfusion, when the patient wants to act as a donor or recipient.

[47], [48]

Differential diagnosis

Chimera is a combined organism that has occurred from more than one zygote. There are a number of pathological cases that have a similar origin. Differential diagnosis is aimed at identifying them.

Consider who is like a chimera, but is not it:

1. Hybrids

• Genetic.
• Somatic.

2. Mosaics

• Chromosomal.
• Genetic.
• Epigenetic.

3. Gynandromorfs
4. Teratogenic effects of varying severity, caused by a disruption in the work of genes responsible for development processes.
5. Natural cases that can be accompanied by mutations

• Frimartines.
• False hermaphroditism.
• Heavy congenital anomalies.
• Genuine hermaphroditism.
• Ovotiestis.
• Abnormal twinness.

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

Treatment of the chimerism in humans

One of the tools of biotechnology is genetic engineering. This science is a complex method aimed at isolating genes from the body, carrying out various manipulations with them, introducing them into different organisms, obtaining recombinant DNA and RNA. The treatment of chimerism, its study and creation, is possible with the help of such genetic technologies.

With the help of genetic engineering, doctors manage the process of chimerization. This is possible with bone marrow transplantation, other organs or blood transfusion. This is a peculiar creation of radiation chimerism in clinical conditions.

With regard to the treatment of chimeras with external manifestations, as, for example, in the case of the Texas child, with mosaic skin color, different eyes color or with additional limbs from the twins trapped 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 the disruption of the socialization process. In this case, genetic changes, that is, the removal of one of the strands of DNA is 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 there are currently no accessible and safe methods for tracing the development of embryos in the mother's womb.

But it is possible to prevent chimerism caused by posttransfusion procedures (bone marrow transplant, organs, blood transfusion). Genetic engineering is used in couples who have a high risk of having children with genetic pathologies. In this case, to prevent mutations in the embryo, additional cells are put in, which normalize the chromosome set of the unborn child.

[49], [50], [51], [52], [53], [54], [55], [56], [57], [58]

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 it is a blood chimera, then during a lifetime a person may never know that he has two sets of DNA. This is due to the fact that special investigations are needed to identify the anomaly and in most cases this type of disorder does not have external signs. If the chimerization is associated with artificial methods, then its forecast is difficult to determine. Thus, when a bone marrow transplant is performed, the patient may have a blood group, a Rh factor and some features of the exterior (eye color, hair) that the donor had.

[59], [60]