Human Heredity 11th Edition by Michael Cummings

Exercise 27

Hypothetical metabolic disease in which protein E is not produced. Lack of protein E causes intellectual disability in humans. Protein E's function is not known, but it is found in all cells of the body. Skin cells from eight individuals who cannot produce protein E were taken and grown in culture. The defect in each of the individuals is the result of a single recessive mutation. Each individual is homozygous for her or his mutation. The cells from one individual were grown with the cells from another individual in all possible combinations of the two. After a few weeks of growth, the mixed cultures were assayed for the presence of protein E. The results are given in the following table. A plus sign means that the two cell types produced protein E when grown together (but not separately); a minus sign means that the two cell types still could not produce protein E.
A) Assuming that these individuals represent all possible mutants in the synthesis of protein E, how many steps are there in the pathway to protein-E production?
B) Compounds A, B, C, and D are known to be intermediates in the pathway for production of protein E. To determine where the block in protein-E production occurred in each individual, the various intermediates were given to each individual's cells in culture. After a few weeks of growth with the intermediate, the cells were assayed for the production of protein E. The results for each individual's cells are given in the following table. A plus sign means that protein E was produced after the cells were given the intermediate listed at the top of the column. A minus sign means that the cells still could not produce protein E even after being exposed to the intermediate at the top of the column.