Genetics of blood groups and Rhesus factor

Genetics of the Rhesus (Rh) System

The Rhesus factor system is second in clinical significance only to the AB0 system. It is based on the presence of a protein antigen on the surface of erythrocytes, which was first discovered in monkeys and later in humans. This trait is strictly inherited and remains unchanged throughout life.

Genetic control of Rhesus antigen synthesis is carried out by three pairs of non-allelic genes that are closely linked: Cc, Dd, and Ee. They are located on the short arm of the first chromosome. Due to various combinations of these alleles, 27 unique genotypes can form in the human population.

A key role in determining Rhesus status is played by the D gene. It is this gene that determines the trait we call "Rhesus-positive." Inheritance occurs in a dominant manner:

• Rh+ (Rhesus-positive): account for about 85% of the population. Their genotype contains at least one dominant allele (DD or Dd).
• Rh- (Rhesus-negative): occur in 15% of people. This condition is caused exclusively by the recessive homozygote (dd).

Gene position effect and Rhesus factor

An interesting feature of Rhesus factor inheritance is the position effect. This is a specific interaction of non-allelic genes where the final phenotype depends on the physical location of the genes in the chromosome. This phenomenon was first described by American geneticist Alfred Sturtevant in 1925 while studying Drosophila, but it is also clearly manifested in humans.

Since the dominant genes C, D, and E are located in close proximity to each other on the chromosome, their mutual arrangement affects protein expression. Let us take two patients with an identical genotype CcDDEe. Despite the same set of alleles, their phenotypic manifestations will differ depending on the arrangement of genes in the pair of homologous chromosomes:

• Variant A (arrangement C D E / c D e): a large amount of antigen E is synthesized on the erythrocyte membrane, but very little antigen C.
• Variant B (arrangement C D e / c D E): the reverse picture is observed — little antigen E is produced, but a lot of antigen C.

Epistasis and the mystery of the Bombay phenotype

Blood groups can serve as a classic example of epistasis—a type of interaction where a gene from one allelic pair completely suppresses the action of a gene from another pair. The suppressing gene is called an inhibitor (I) or suppressor (Su).

A prime example of recessive epistasis is the Bombay phenotype. Normally, the formation of antigens A and B requires the base substance H. If a person is a recessive homozygote for the gene responsible for this substance (genotype hh), the H molecule simply does not form. As a result, even in the presence of genes for the second or third blood group, antigens A and B cannot be synthesized. The blood type is determined as the first group (0).

Because of this phenomenon, paradoxical cases occur in genetics. For example, in a family where the mother phenotypically had the first blood group (but genetically carried the third group allele and was homozygous for hh — I^BI^Ohh), and the father had the second group (I^AI^OHH), a daughter with the fourth blood group (I^AI^BHh) was born. The child inherited the dominant H gene from the mother, which "unlocked" the hidden I^B gene.

Dominant epistasis also exists. In humans, certain enzymopathies such as phenylketonuria (PKU) and galactosemia are inherited through this mechanism, disrupting the production of vital enzymes.

Complementarity and polygeny

Non-allelic genes can also interact in other ways, affecting either different traits or the same trait.

Complementary (supplementary) interaction implies that the trait appears only when dominant genes from different allelic pairs are present together. A classic example is the inheritance of hearing. One dominant gene is responsible for the formation of the auditory nerve, and another for the development of the cochlea. If a deaf woman with genotype AAbb (no cochlea) and a deaf man with genotype aaBB (no auditory nerve) have a child, they will get the genotype AaBb. Both structures will develop, and hearing will be completely normal. Some diseases, such as retinoblastoma and nephroblastoma, are encoded in a similar way.

Polygeny is a situation where several non-allelic genes work together, enhancing the expression of a single trait. The more dominant alleles in the genotype, the more pronounced the trait.

A great example of polygenic inheritance is skin color. If both parents have chocolate skin color, their children can have black, chocolate, or even white skin color depending on the gene combination. Other human polygenic traits include:

• height and muscle strength;
• hair color;
• blood pressure levels;
• mental abilities.

Class and exam questions

What else to study on this topic

• Mechanisms of complementary interaction in retinoblastoma and nephroblastoma
• Dominant epistasis using enzymopathies as an example (phenylketonuria, galactosemia)
• Polygenic inheritance of quantitative traits (height, blood pressure, intelligence)
• Regulatory interactions of non-allelic genes

Other topics in the "Additional Topics" section

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