Question

1. The ABO blood type is determined by different alleles for a gene that codes for an enzyme. How do the mutations in the alleles lead to the different blood types?
   Recall that the mutations = alleles affect the active site of the enzyme.

Answer 1

The ABO blood type is determined by a single gene that comes in 3 versions, A, B, and O. The difference between A and B is of 7 bases while O is missing a base, making the difference between A and O as one base. Though only one base is changed, the entire reading sequence changes which are enough to cause mutations.

Functional alleles at ABO genetic locus code for glycosyltransferases. Glycosyltransferases participate in the assembly of glycan units of glycoproteins and glycolipids present in cell membranes of erythrocytes and other cells and glycoproteins of some secretions. The mutation of single ABO gene gives rise to many products. The three mutations give rise to A, B, and O specificities. Two mutations (substitutions) affect the recognition and binding of donor nucleotide sugar substrate. These mutations change the specificity of an enzyme from N-acetylgalactosaminyltransferase i.e., the A enzyme to galactosyltransferase i.e., the B enzyme. Now, these glycosyltransferases introduce either alpha 1,3 N- acetylgalactosamine (A) or alpha 1,3 galactose (B) at the ends of H glycan chains. These two mutations define the A and B epitopes. Let's talk about the third mutation now. The third mutation is a deletion within 5' region of catalytic domain causing a frameshift and completely inactivating the enzyme. H glycan remains unmodified which defines the O epitope.