Question

With respect to genetics, ABO blood types are controlled by a single gene designated I, which has three alleles. The I A allele gives blood type A, I B gives blood type B, and i gives blood type O. The I A and I B alleles are codominant and i allele is recessive to both the I A and I B alleles.

Aside from the I alleles, there are two other genes that when mutated affect ABO blood type inheritance. The first mutant is recessive to wild type and is designated x. A homozygous xx individual is phenotypically O for blood type no matter what the genotype is of the I gene. For example, I A /I A x/x or I B /I B x/x individuals are O type. The second mutant, is dominant to the wild type Y allele and is designated Yd . An individual carrying a Yd allele is phenotypically blood type O no matter what the genotype is of the I gene. For example, an I A /I A Y/Yd or I B /I B Y/Yd individuals is O.

b. Propose a biochemical model that explains the phenotype of individuals carrying the dominant Yd mutant allele? This model must explain why this mutation is dominant to the wild type Y allele

Answer 1

To understand the biochemical basis of above problem, lets see the biochemical basis of ABO blood group. There is a chemical moiety known as H-Substance (H substance contains 3 sugar molecules chemically linked together: Galactose, N-acetyl glucosamine and fucose) which is attached to lipids of plasma membrane of RBCs of almost all individuals. To this H- substance different sugars attached determine different blood group antigen amd ultimately the blood group. If there is absence of any addition of sugar on H- substance, the result is the absence of antigen (as in case of person with O blood group).

Now, if in presence of dominant Y allele,the phenotype come to be O, irrespective of the genotype of I- gene, it clearly shows the case of Dominant Epistasis.

Epistasis is a kind of gene interaction where one gene present at one locus masks/modifies the expression of another gene present at distinct locus. Also, when the dominant allele of one gene masks the expression of either of the allele of the second gene, phenomenon is termed as Dominant Epistasis.

Since Y-gene can express itself in heterozygous condition (Y/Yd)and also masks the genotype of I-gene , it clearly is dominant and showing Dominant Epistasis. In presence of dominant Y-gene the effect of I- gene gets masked and no terminal sugar is attached to H-Substance, hence resulting in O blood group phenotype.

Hope you understood the concept. Thanks.