Human ABO blood type is determined by three alleles, two of which (I^A and I^B) produce gene products that modify the H antigen produced by protein activity of an independently assorting H gene. A rare abnormality known as the 'Bombay phenotype' is the result of epistatic interaction between the gene for the ABO blood group and the H gene. Individuals with the Bombay phenotype appear to have blood type O based on the inability of both anti-A antibody and anti-B antibody to detect an antigen. The apparent blood type O in Bombay phenotype is due to the absence of H antigen as a result of homozygous recessive mutations of the H gene. Individuals with the Bombay phenotype have the hh genotype. Use the information above to make predictions about the outcome of the cross shown below.
IᴬIᴮHh×IᴬIᴮHh

Verified step by step guidance

1. Determine the genotypes of the parents. Both parents are IᴬIᴮHh, meaning they are heterozygous for the H gene (Hh) and heterozygous for the ABO blood group alleles (IᴬIᴮ).
2. Set up a Punnett square for the H gene. Since both parents are Hh, the possible genotypes for their offspring are HH, Hh, and hh. The hh genotype results in the Bombay phenotype, regardless of the ABO alleles.
3. Set up a separate Punnett square for the ABO alleles. Since both parents are IᴬIᴮ, the possible genotypes for their offspring are IᴬIᴬ, IᴬIᴮ, IᴮIᴮ, and ii. These genotypes correspond to blood types A, AB, B, and O, respectively, but only if the H antigen is present (H allele).
4. Combine the results of the two Punnett squares. For each combination of ABO genotype and H genotype, determine the phenotype. If the H genotype is hh, the individual will have the Bombay phenotype (appearing as blood type O) regardless of their ABO genotype.
5. Calculate the probabilities of each phenotype by multiplying the probabilities from the ABO Punnett square and the H gene Punnett square. For example, the probability of a Bombay phenotype (hh) is determined by the hh genotype (1/4) combined with any ABO genotype.

Key Concepts

ABO Blood Group System

The ABO blood group system is determined by the presence of specific antigens on the surface of red blood cells, which are encoded by three alleles: I^A, I^B, and i. The I^A and I^B alleles are co-dominant, meaning that both can be expressed simultaneously, resulting in blood types A (I^A I^A or I^A i), B (I^B I^B or I^B i), AB (I^A I^B), or O (ii). Understanding this system is crucial for predicting blood type inheritance in offspring.

Epistasis

Epistasis refers to the interaction between genes where the expression of one gene is affected by one or more other genes. In the case of the Bombay phenotype, the H gene's product is necessary for the expression of A and B antigens. Individuals with the hh genotype lack the H antigen, leading to a phenotype that appears as blood type O, despite having I^A and I^B alleles. This concept is essential for understanding how gene interactions can influence phenotypic outcomes.

Genotype and Phenotype

Genotype refers to the genetic constitution of an individual, while phenotype is the observable physical or biochemical characteristics resulting from the genotype and environmental influences. In the context of the Bombay phenotype, the genotype hh leads to the absence of the H antigen, resulting in a phenotype that is indistinguishable from blood type O. This distinction is vital for predicting the phenotypic ratios in genetic crosses.