Lecture 6: Genetics and Transfusion Flashcards
What is the function of Isoagglutinogen (I) and how many alleles does it have?
- Isoagglutinogen encodes an enzyme and has three different alleles: IA, IB, and IO.
- These alleles result in six possible genotypes: AO, AA, BB, BO, AB, and OO.
What is the significance of the allele O (Little i)?
Recessive to the other alleles and results in a non-functional enzyme.
What enzyme activity does the IA allele encode?
N-acetyl galactosamine transferase, which is responsible for transferring N-acetyl galactosamine onto carbohydrates and lipids.
What does the IB allele encode, and how does it differ from IA?
- The IB allele encodes a modified enzyme capable of transferring galactose but not acetyl galactosamine.
- This enzyme is active in the Golgi apparatus during red blood cell (RBC) development.
What is the function of the IO allele?
The IO allele encodes a non-functional enzyme, resulting in an absence of enzyme activity.
When are the enzymes encoded by IA, IB, and IO alleles active during RBC development?
These enzymes are active in the Golgi apparatus as RBCs differentiate, where they decorate lipids within the Golgi, influencing the composition of the RBC membrane.
What antigens are present in blood types A, B, and O?
- Blood types A and B have antigens corresponding to the respective transferases (A and B antigens), while blood type O has no active transferase and lacks these antigens.
- However, even blood type O presents an antigen known as the H antigen.
What is the composition of the H antigen?
The H antigen consists of galactose (2), N-acetylglucosamine, and fucose.
How does the activity of the encoded enzymes by blood types A, B, and O affect the decoration of the H antigen?
- Type A transferase adds Gal-NAC to the H antigen
- Type B transferase transfers galactose onto it
- Type O lacks an active enzyme, resulting in no carbohydrate decoration.
What distinguishes the carbohydrate decorations on the H antigen among blood types A, B, and O?
Blood type A transfers Gal-NAC, blood type B transfers galactose, while blood type O lacks enzyme activity, leading to no carbohydrate decoration.
What are Glycosphingolipids?
Lipid molecule found in cell membranes, including the membrane of red blood cells (RBCs). They consist of a ceramide lipid backbone with one or more carbohydrate (sugar) chains attached.
How do Glycosphingolipids contribute to the structure of the RBC membrane?
- Glycosphingolipids are integral components of the RBC membrane, where they are positioned within the lipid bilayer.
- Contribute to the overall structure and function of the membrane by participating in cell signaling, adhesion, and recognition processes.
What is the significance of Glycosphingolipids being decorated lipids?
- Being decorated lipids means that glycosphingolipids have carbohydrate chains attached to them.
- These carbohydrate chains can vary in length and composition, influencing the properties and interactions of the glycosphingolipids within the membrane.
How are Glycosphingolipids related to glycosylated proteins in the RBC membrane?
- Both Glycosphingolipids and glycosylated proteins are involved in carbohydrate decoration within the RBC membrane.
- While glycosylated proteins are proteins with attached carbohydrate chains, glycosphingolipids themselves serve as a platform for carbohydrate decoration in the membrane.
What is the Bombay Phenotype?
- Rare genetic condition characterized by the absence of ABO blood group antigens on RBCs, despite having the genetic potential to produce them.
- Individuals with the Bombay phenotype cannot produce the H antigen, which serves as a precursor for the ABO blood group antigens.
Why can’t you always predict parentage from blood types?
- Individuals with the Bombay phenotype may possess alleles for A, B, or AB blood types, but they lack the H antigen necessary for the expression of ABO blood group antigens.
- RESULT: their blood type appears as O (type O-like) even if they genetically carry A, B, or AB alleles.
What is the role of the H antigen in the ABO blood group system?
- The H antigen, encoded by the FUT1 gene, serves as a precursor for the ABO blood group antigens.
- It acts before the A and B transferases (encoded by the ABO gene) to add fucose residues to glycoproteins and glycolipids on the surface of RBCs.
- Without the H antigen, the ABO blood group antigens cannot be properly formed.
What is the role of FUT1 in the ABO blood group system?
- FUT1 (fucosyltransferase 1) is involved in the production of the H antigen, which serves as a precursor for the ABO blood group antigens.
- It adds fucose residues to glycoproteins and glycolipids on the surface of RBCs, allowing for the subsequent addition of A and B antigens.
What is the function of FUT2 in relation to blood group antigens?
FUT2 (fucosyltransferase 2), also known as the secretor gene, is responsible for the secretion of ABO blood group antigens into bodily fluids such as saliva, mucus, and other mucosal secretions.
How does the secretor status affect health risks?
- Non-secretors, individuals with non-functional FUT2 alleles, are unable to secrete ABO blood group antigens into their bodily fluids.
- This non-secretor status has been associated with an increased risk of various health conditions, including
- Oral diseases
- Asthma
- Diabetes
- Alcoholism
- Infections
- Autoimmune diseases
What happens if an individual is Rh-negative and carrying an Rh-positive fetus?
Rh-negative individual may start to generate an immune response against the Rh-positive fetal antigens.
Do Rh-negative individuals naturally produce antibodies against Rh-positive antigens?
No, but, during pregnancy with an Rh-positive fetus, exposure to fetal Rh-positive blood may trigger the production of antibodies against these antigens.
What are the consequences of developing antibodies against Rh-positive antigens during pregnancy?
- In subsequent pregnancies with Rh-positive fetuses, the maternal antibodies generated during the first pregnancy can cross the placenta and enter the fetal circulation.
- This can lead to hemolytic disease of the newborn (HDN), where maternal antibodies attack and destroy the red blood cells of the Rh-positive fetus, potentially causing severe complications or even death for the baby.
What is the treatment for Rh incompatibility?
- The mother receives anti-Rh(D) immunoglobulin (anti-D) during pregnancy and after delivery to prevent the sensitization of Rh-negative mothers to Rh-positive fetal blood cells.
- Helps to prevent the development of antibodies against Rh-positive antigens in future pregnancies.
- If hemolytic disease of the newborn (HDN) occurs, the affected child may require blood transfusions with compatible blood.
