Genetics of cytidine monophospho-N-acetyineuraminic acid hydroxylase (CMAH) : dottorato di ricerca in produzioni animali

The discovery of the human blood groups, its importance, from the classical method to the DNA-based assays of testing. On the surface of the membrane of the red blood cells, carried by proteins, glycoproteins or glycolipid, are present inherited ad polymorphic molecules that determinate the different blood types. These molecules are called antigens, substances that elicit an immune system respond, binding specifically an antibody: they can be sugars (for example ABO blood group) or proteins (as RH system) (Dean L 2005 book). The first discover of a blood group was made in 1900 by Karl Landsteiner, who find out the antigens A and B of the ABO system. Only in the second part of 20th century was defined the structure and biosynthesis of carbohydrate blood group antigens. A total of 29 blood group systems are now recognized by the International Society of Blood Transfusion and 27 are genetically characterized (Daniels 2005) The role played by the molecules that define the blood types are still not unknown for a part of them. Almost all blood group-specifying genes are expressed in erythroid tissues and their products are either membrane-associated protein antigens or enzymes, glycosyltransferases, which synthesize membrane-associated carbohydrates which also define the antigenic epitopes. In a few cases the product is adsorbed to the erythocyte surface from plasma (Lewis, Chido-Rodgers antigens). Products of some genes are confined to erythroid tissues exclusively, whereas others show a more wide distribution and are present on surfaces of other cells or in soluble forms in the body fluids (Blumenfeld OO 2004). ABO group system is the most important blood group because of the reactions that can occur during transfusions. Other blood group system as Rh, Kell, Duffy and Kidd play a more important role in the HDN (hemolytic disease of the newborn). Hemagglutination is the serological test that is normally performed for blood group antibodies and antigens, however, the modern technology in molecular biology allow now to genotype the blood group. The advantages of the DNA testing in human are several: • DNA can be stably isolated, with non invasive procedure, from any nucleated cells in the body, as for example buccal epithelial cell or cells in urine. • DNA test can identified a fetus not at risk for HDNA better than the hemoagglutinin test which gives only an indirect indication of the risk and severity. Furthermore the fetal DNA for the prenatal RH genotyiping test can be easily obtained from mother’s pheripheral blood or trancervical samples (Avent 2000).• The molecular analysis can identify easily more variations than hemoagglutinations, such for example the partial D and weak D, and aberrant e and E antigens in the RH system. • DNA typing has a higher resolution especially for distinguishing inherited variant from acquired phenotypes after one or multiple transfusion. • DNA test can be useful in antigen-typing donor blood for antibody identification reagent panel. (Reid 2003) • Useful for forensic purposes. Still al lot of research, using the most modern techniques as Real-time PCR and microarray, is going on in this field in order to improve the reliability and also the cost-efficiency of blood group genotyping, (Wagner 1998) but this will be probably the future.