Blood group inheritance

Biochemical structure and phenotypes of the AB0 system

Every person's blood has a unique profile due to specific erythrocyte antigens. In modern medical practice, more than thirty different blood group systems are distinguished, but the AB0 system remains fundamental and clinically most significant. Within this classification, four main phenotypes are traditionally defined:

1. Group I — 0 (I)
2. Group II — A (II)
3. Group III — B (III)
4. Group IV — AB (IV)

At the biochemical level, the antigens located on the erythrocyte membrane are three types of glycoproteins. Their specificity and main difference are determined by the structure of the non-protein oligosaccharide group. This carbohydrate moiety invariably includes components such as fucose, galactose, N-acetylgalactosamine, and N-acetylglucosamine.

To determine a patient's phenotype, laboratory diagnostics employ the method of mixing erythrocytes with standard sera of four groups in vitro (outside a living organism). The sera used contain natural antibodies. The final result is evaluated by the specialist based on the presence or complete absence of agglutination — the characteristic clumping of red blood cells.

Genetic determination

The inheritance of specific phenotypes is strictly determined by gene combinations. The formation of blood groups is controlled by three main alleles.

• The $I^0$ gene is recessive; it is unable to encode the development of an antigen. Accordingly, the first blood group is formed only with the homozygous genotype $I^0I^0$.
• The $I^A$ allele encodes the development of antigen A and is dominant relative to the $I^0$ allele. Thus, the second group can be represented by both the homozygous $I^AI^A$ and heterozygous $I^AI^0$ genotypes.
• A similar genetic situation is observed for the third group: the $I^B$ allele (encoding antigen B) dominates over the first group, so genotypes $I^BI^B$ and $I^BI^0$ are possible.

The fourth group arises from the joint inheritance of two dominant alleles — $I^AI^B$.

Atypical inheritance: a clinical case

In medical genetics, cases occur that contradict classical Mendelian inheritance. A telling example is a situation where a child with the fourth blood group AB (IV) is born to a mother with the first group 0 (I) and a father with the second A (II).

The solution to this phenomenon lies in the phenomenon of recessive epistasis. The mechanism is as follows:

1. For the successful synthesis of any agglutinogens (A or B), a special precursor protein (substrate) is required.
2. The production of this substrate is controlled by an independent dominant H gene.
3. If a person inherits the recessive h allele in a homozygous state (`hh`), the synthesis of the precursor protein is completely blocked.

As a result of the `hh` genotype, antigens A and B cannot be synthesized, even if dominant alleles $I^A$ or $I^B$ are present in the genotype. Phenotypically, such a patient's blood is determined as group I due to the absence of agglutinogens.

Analysis of the described clinical case shows that the woman genetically inherited the $I^B$ allele from her mother and $I^0$ from her father (her genotype is $I^B I^0$). However, phenotypically she had blood group I, since the $I^B$ gene was suppressed by the recessive h gene in the homozygous state (`hh`). The child received this hidden $I^B$ allele from the mother, the $I^A$ allele from the father, and also a normal dominant H gene from the father. This restored the synthesis of the precursor and allowed the fourth blood group ($I^AI^B$) to manifest.

Class and exam questions

What else to study on this topic

• Biochemical role of fucose and galactose in the structure of glycoproteins
• Mechanism of interaction of natural serum antibodies with antigens
• Genetics of precursor protein formation (H gene)
• Types of epistasis and atypical trait inheritance

Other topics in «Patterns of Inheritance (Nuclear Genes)»

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.