Cis AB

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Regular (trans) AB versus cis AB
AB&O Regular Inheritance.svg
Inheritance of regular ABO for AB & O parents
CisAB.svg
Cis AB inheritance, scenario 1.1: in the AB parent, one allele is AB and other is O

Cis AB is a type of rare mutation in the ABO gene. It happens when the transferase allele contains a mix of amino acids from either A or B alleles, producing a bifunctional enzyme that can produce both types of antigens, usually with one weaker than the other. This results in a serum test result much like the standard, separate (trans) AB phenotype, although the weaker antigen can occasionally fail to be detected. It complicates the basic inheritance pattern (as the allele comes from one parent only) and blood-transfusion compatibility matching for ABO blood typing.

Contents

Different DNA mutations of either type A or Type B alleles change amino acids in enzyme transferase A or B, homologous enzymes differing in only four of 354 amino acids (R176G, G235S, L266M, and G268A). A single change in ABO gene DNA could switch type B to type A and then, a new hybrid enzyme can produce both weak B and A2 (in serum test, A2B, and A2B3). The most common mutation is an A105 allele variation in exon 7 nucleotide position G803C changing glycine (type A) to alanine (type B). Another 8 alleles are reported in BGMUT, most recently in China and Taiwan. Some Cis-AB carriers need components like washed red blood cells or autotransfusion of serum and blood.

Cis-AB type was studied first in humans in Japan (Shikoku Island) and South Korea (Gwangju area) where this rare type is more common (Chinese coast provinces and Taiwan also), although it is seen in a few European families (from France, Spain, Belgium, Germany, and Poland). In the year 2004, the American Red Cross described a family in Nebraska with a father of type cis-AB negative, a mother type O and their baby of type cis-AB. Since then, several cases in the United States have been reported. [1] Antigen expression is weaker than A1 or B.

Scenarios

When one parent carries a Cis AB allele, the other allele can be any of O, A or B. The phenotype of this parent is always AB, but the children will inherit either the AB or the other allele from this parent.

  1. If the other parent is O phenotype (OO genotype) the three possible scenarios for the blood group of children of a Cis AB carrier (and a fourth unlikely scenario) are:
    1. The second allele is O: children are either AB or O
    2. Second allele is A: Children are either AB or A
    3. Second allele is B: Children are either AB or B
    4. A very rare 4th possibility exists: if the other allele is also Cis AB then the children will be always AB irrespective whatever the other parent is, because they will have one cis AB allele from this parent.
  2. If the other parent is type A, depending on whether this parent is genotypically AA or AO and what the other allele is in the Cis Ab carrying parent, the following scenarios are possible:
    1. Other parent is AO and the second allele is O: The children are either AB or A or O
    2. Other parent is AA and the second allele is O: The children are either AB or A
    3. Other parent is AO and the second allele is A: The children are either AB or A
    4. Other parent is AA and the second allele is A: The children are either AB or A
    5. Other parent is AO and the second allele is B: The children are either AB or B
    6. Other parent is AA and the second allele is B: The children are always AB
    7. Rare situation: If the other allele is also cis AB: The children are always AB
  3. Likewise, similar scenarios for the other parent being type B are:
    1. Other parent is BO and the second allele is O: The children are either AB or B or O
    2. Other parent is BO and the second allele is A: The children are either AB or A
    3. Other parent is BO and the second allele is B: The children are always AB or B
    4. Other parent is BB and the second allele is B: The children are either AB or B
    5. Other parent is BB and the second allele is O: The children are either AB or B
    6. Other parent is BB and the second allele is A: The children are always AB
    7. Rare situation: If the other allele is also cis AB: The children are always AB

ABO inheritance is generally derived assuming the children are not the rare Bombay phenotype, which would require both parents to be carriers of it.

Real life implications

Maternity and paternity disputes

When testing paternity or maternity by ABO blood group alone, it is possible to have a paradoxical result in the rare instance that a cis-AB genotype is involved.[ citation needed ] For example, (scenario 1.1 above) a child of a cis AB individual (who will test as a regular AB phenotype) and an O individual will be either AB or O instead of the usual A or B (see diagram above).[ citation needed ]

Differential diagnosis

If the child of an AB and an O individual is O (the green-colored offspring in the scenario 1 image above), then a rare alternative possibility is that the parents were carriers (heterozygous) for the Bombay phenotype (Hh) and the child is a Bombay (hh) homozygous by genotype thus expressing Bombay phenotype also called Oh where, despite the presence of the ABO alleles, the substrate from which those antigens are made is not made and thus A, B and even O antigen are not expressed at all and are completely absent from the red cells.

Related Research Articles

An allele is one of two, or more, forms of a given gene variant. For example, the ABO blood grouping is controlled by the ABO gene, which has six common alleles. Nearly every living human's phenotype for the ABO gene is some combination of just these six alleles. An allele is one of two, or more, versions of the same gene at the same place on a chromosome. It can also refer to one of multiple different sequence variations of several-hundred base-pairs long or longer regions of the genome that code for proteins. Alleles can come in different extremes of size. At the lowest extreme, an allele can be a single nucleotide polymorphism (SNP). At higher extremes, it can be up to several thousand base-pairs long. Most alleles result in little or no observable change in the function of the protein the gene codes for.

Blood type Classification of blood

A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.

Dominance (genetics) One gene variant masking the effect of another in the other copy of the gene

In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes (autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child. Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant nor recessive. Additionally, there are other forms of dominance such as incomplete dominance, in which a gene variant has a partial effect compared to when it is present on both chromosomes, and co-dominance, in which different variants on each chromosome both show their associated traits.

Duffy antigen system Human blood group classification

Duffy antigen/chemokine receptor (DARC), also known as Fy glycoprotein (FY) or CD234, is a protein that in humans is encoded by the ACKR1 gene.

ABO blood group system Classification of blood types

The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. In human blood transfusions it is the most important of the 38 different blood type classification systems currently recognized. A mismatch in this, or any other serotype, can cause a potentially fatal adverse reaction after a transfusion, or an unwanted immune response to an organ transplant. The associated anti-A and anti-B antibodies are usually IgM antibodies, produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses.

In genetics, complementation occurs when two strains of an organism with different homozygous recessive mutations that produce the same mutant phenotype have offspring that express the wild-type phenotype when mated or crossed. Complementation will ordinarily occur if the mutations are in different genes. Complementation may also occur if the two mutations are at different sites within the same gene, but this effect is usually weaker than that of intergenic complementation. In the case where the mutations are in different genes, each strain's genome supplies the wild-type allele to "complement" the mutated allele of the other strain's genome. Since the mutations are recessive, the offspring will display the wild-type phenotype. A complementation test can be used to test whether the mutations in two strains are in different genes. Complementation ordinarily will occur more weakly or not at all if the mutations are in the same gene. The convenience and essence of this test is that the mutations that produce a phenotype can be assigned to different genes without the exact knowledge of what the gene product is doing on a molecular level. The complementation test was developed by American geneticist Edward B. Lewis.

A null allele is a nonfunctional allele caused by a genetic mutation. Such mutations can cause a complete lack of production of the associated gene product or a product that does not function properly; in either case, the allele may be considered nonfunctional. A null allele cannot be distinguished from deletion of the entire locus solely from phenotypic observation.

In ABO hemolytic disease of the newborn maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

The Kidd antigen system are proteins found in the Kidd's blood group, which act as antigens, i.e., they have the ability to produce antibodies under certain circumstances. The Jk antigen is found on a protein responsible for urea transport in the red blood cells and the kidney. They are important in transfusion medicine. People with two Jk(a) antigens, for instance, may form antibodies against donated blood containing two Jk(b) antigens. This can lead to hemolytic anemia, in which the body destroys the transfused blood, leading to low red blood cell counts. Another disease associated with the Jk antigen is hemolytic disease of the newborn, in which a pregnant woman's body creates antibodies against the blood of her fetus, leading to destruction of the fetal blood cells. Hemolytic disease of the newborn associated with Jk antibodies is typically mild, though fatal cases have been reported.

Rh blood group system Human blood group systems

The Rh blood group system is a human blood group system. It contains proteins on the surface of red blood cells. After the ABO blood group system, it is the most likely to be involved in transfusion reactions. The Rh blood group system consists of 49 defined blood group antigens, among which the five antigens D, C, c, E, and e are the most important. There is no d antigen. Rh(D) status of an individual is normally described with a positive or negative suffix after the ABO type. The terms Rh factor, Rh positive, and Rh negative refer to the Rh(D) antigen only. Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh(D) and Rh antigens confer significant risk of hemolytic disease of the fetus and newborn.

hh, or the Bombay blood group, is a rare blood type. This blood phenotype was first discovered in Bombay by Dr. Y. M. Bhende in 1952. It is mostly found in the Indian sub-continent and parts of the Middle East such as Iran.

Animal erythrocytes have cell surface antigens that undergo polymorphism and give rise to blood types. Antigens from the human ABO blood group system are also found in apes and Old World monkeys, and the types trace back to the origin of humanoids. Other animal blood sometimes agglutinates with human blood group reagents, but the structure of the blood group antigens in animals is not always identical to those typically found in humans. The classification of most animal blood groups therefore uses different blood typing systems to those used for classification of human blood.

The MNS antigen system is a human blood group system based upon two genes on chromosome 4. There are currently 50 antigens in the system, but the five most important are called M, N, S, s, and U.

P1PK blood group system

P1PK is a human blood group system based upon the A4GALT gene on chromosome 22. The P antigen was first described by Karl Landsteiner and Philip Levine in 1927. The P1PK blood group system consists of three glycosphingolipid antigens: Pk, P1 and NOR. In addition to glycosphingolipids, terminal Galα1→4Galβ structures are present on complex-type N-glycans. The GLOB antigen is now the member of the separate GLOB blood group system.

The Lewis antigen system is a human blood group system. It is based upon two genes on chromosome 19: FUT3, or Lewis gene; and FUT2, or Secretor gene. Both genes are expressed in glandular epithelia. FUT2 has a dominant allele which codes for an enzyme and a recessive allele which does not produce a functional enzyme. Similarly, FUT3 has a functional dominant allele (Le) and a non-functional recessive allele (le).

Ii antigen system Human blood group system

The Ii antigen system is a human blood group system based upon a gene on chromosome 6 and consisting of the I antigen and the i antigen. The I antigen is normally present on the cell membrane of red blood cells in all adults, while the i antigen is present in fetuses and newborns.

ABO (gene) Protein-coding gene in the species Homo sapiens

Histo-blood group ABO system transferase is an enzyme with glycosyltransferase activity, which is encoded by the ABO gene in humans. It is ubiquitously expressed in many tissues and cell types. ABO determines the ABO blood group of an individual by modifying the oligosaccharides on cell surface glycoproteins. Variations in the sequence of the protein between individuals determine the type of modification and the blood group. The ABO gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

Secretor status refers to the presence or absence of water-soluble ABO blood group antigens in a person's bodily fluids, such as saliva, tears, breast milk, urine, and semen. People who secrete these antigens in their bodily fluids are referred to as secretors, while people who do not are termed non-secretors. Secretor status is controlled by the FUT2 gene, and the secretor phenotype is inherited in an autosomal dominant manner, being expressed by individuals who have at least one functioning copy of the gene. The non-secretor phenotype (se) is a recessive trait. Approximately 80% of Caucasian people are secretors, while 20% are non-secretors. Non-secretors have reduced susceptibility to the most common strains of norovirus. Expression of the antigens in the Lewis blood group is also affected by secretor status: non-secretors cannot produce the Le(b) antigen.

The Junior blood group system is a human blood group defined by the presence or absence of the Jr(a) antigen, a high-frequency antigen that is found on the red blood cells of most individuals. People with the rare Jr(a) negative blood type can develop anti-Jr(a) antibodies, which may cause transfusion reactions and hemolytic disease of the newborn on subsequent exposures. Jr(a) negative blood is most common in people of Japanese heritage.

Blood compatibility testing Testing to identify incompatibilities between blood types

Blood compatibility testing is conducted in a medical laboratory to identify potential incompatibilities between blood types in blood transfusion. It is also used to diagnose and prevent some complications of pregnancy that can occur when the baby has a different blood group from the mother. Blood compatibility testing includes blood typing, which detects the antigens on red blood cells that determine a person's blood type; testing for unexpected antibodies against blood group antigens ; and, in the case of blood transfusions, mixing the recipient's plasma with the donor's red blood cells to detect incompatibilities (crossmatching). Routine blood typing involves determining the ABO and RhD type, and involves both identification of ABO antigens on red blood cells and identification of ABO antibodies in the plasma. Other blood group antigens may be tested for in specific clinical situations.

References

  1. ↑ Yazer, Mark H.; Olsson, Martin L.; Palcic, Monica M. (2006). "The cis-AB Blood Group Phenotype: Fundamental Lessons in Glycobiology". Transfusion Medicine Reviews. 20 (3): 207–217. doi:10.1016/j.tmrv.2006.03.002. PMID   16787828.

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