Blood type information is definitively contained within the genetic code, although it has traditionally been determined by testing red blood cell samples. Blood type is not merely a surface property of a cell; it is a physical characteristic dictated by the underlying instructions found in our DNA. While conventional methods look at the physical antigens present on the cell surface, genetic testing examines the specific sequence of the genes that code for these antigens.
The Genetic Blueprint of Blood Types
Blood type is inherited, determined by specific genes passed down from our parents, with the most recognized system being the ABO blood group. The gene responsible for the ABO system is located on the long arm of chromosome 9, at a position designated 9q34.2. This gene contains instructions for creating an enzyme called a glycosyltransferase, which adds specific sugar molecules, known as antigens, to the surface of red blood cells.
The ABO gene exists in three common variations, or alleles: A, B, and O. The A allele instructs the enzyme to create the A antigen, and the B allele instructs it to create the B antigen, while the O allele is essentially a non-functional copy that results in no A or B antigen being produced. Since every person inherits one allele from each parent, the combination of these two alleles determines the ultimate blood type. For instance, a person with an A allele and a B allele expresses both antigens, resulting in type AB blood, an example of codominance.
The O allele is recessive, meaning it only results in Type O blood if a person inherits an O allele from both parents. A person with one A allele and one O allele will still have Type A blood, as the dominant A allele is expressed on the cell surface.
Beyond the ABO system, the Rh factor, which determines whether blood is positive or negative, is controlled by a different set of genes, primarily the RHD gene. The RHD gene provides the blueprint for the D antigen, a protein on the red blood cell surface. If a person inherits even one copy of the dominant positive allele, they will be Rh-positive, while a person must inherit two copies of the recessive negative allele to be Rh-negative. Molecular analysis of both the ABO and RHD genes allows for precise determination of the complete blood type, such as A-positive or O-negative.
Serology Versus DNA Genotyping
The traditional method for blood typing, known as serology, relies on the principle of agglutination, or clumping, to identify blood group antigens. This process involves mixing a sample of the patient’s red blood cells with specific antibodies against A, B, and Rh antigens. If the corresponding antigen is present, the antibodies bind to it, causing the red cells to visibly clump together.
Serology is fast, relatively inexpensive, and highly reliable for routine pre-transfusion screening because it directly assesses the phenotype, which is the physical expression of the antigen on the cell surface. However, this method has limitations, particularly when the red blood cells are compromised or if the person has received numerous blood transfusions. Patients who are heavily transfused will have a mix of their own red cells and donor red cells, which can complicate or mask the true result of the serological test.
DNA genotyping offers an alternative approach by analyzing the genotype, or the specific sequence of the ABO and RHD genes. Techniques like Polymerase Chain Reaction (PCR) or DNA sequencing are used to examine the genetic code for the exact alleles present. This method can be performed on any cell containing a nucleus, such as white blood cells or cheek swab cells, and does not require intact red blood cells.
A significant advantage of genotyping is its ability to distinguish between heterozygous and homozygous genotypes, which is impossible with standard serology. For example, serology can only confirm that a person is Type A (phenotype A), but genotyping can reveal if they are genetically A/A or A/O. This level of detail is important in resolving complex typing issues and understanding inheritance patterns. Genotyping is not affected by recent transfusions or conditions like autoimmune hemolytic anemia, which can interfere with the antigen-antibody reactions of serological testing.
Practical Applications of Genetic Blood Typing
Genetic blood typing is primarily used in situations where conventional serology is inconclusive, unreliable, or impossible to perform. One of the most important applications is in transfusion medicine for patients who require chronic transfusions, such as those with sickle cell disease or thalassemia. Because these patients have a constant mix of their own and donor red blood cells, serological typing of their native blood type is often impossible.
Genotyping ensures accurate antigen matching for these individuals, which is necessary to prevent the development of harmful antibodies against donor blood. It is also used to resolve discrepancies when a patient’s serological results do not match their expected blood type or when identifying rare blood types for which commercial serology reagents are not widely available. By sequencing the DNA, experts can precisely identify novel or weakened antigen variants.
In forensics, DNA typing is a powerful tool because genetic material can be recovered from degraded or historical biological samples where red blood cells are long gone. The genetic sequence of the ABO or Rh genes can be determined from minute amounts of DNA. Genetic typing is also used in prenatal medicine to determine the Rh status of a fetus using cell-free fetal DNA from a pregnant Rh-negative mother’s blood sample. This non-invasive assessment helps medical professionals determine the risk of Hemolytic Disease of the Fetus and Newborn, allowing for targeted preventative treatment.