Chapter 10, Problem 36P

Figure 10.26 on p. 366 portrayed the analysis of Miller syndrome through the sequencing of four complete genomes: those of a brother and sister both affected by the disease, and of both their parents.

a. Researchers made the assumption that Miller syndrome is a recessive trait. Could Miller syndrome instead be due to a dominant mutation? If so, what scenarios would make this possible?

b. Why is it highly unlikely that Miller syndrome in this family is due to de novo mutations that occurred in the germ line of the mother, or of the father, or of both parents? Describe a scenario based on your understanding of cell divisions in human ovaries or testes (see Figs. 4.18 and 4.19 on pp. 107 and 108) that make the de novo mutation hypothesis at least theoretically possible even if very unlikely

c. On Fig. 10.26b, indicate the location on chromosome 16 closest to the DHOD gene at which recombination took place during meiosis in one of the parents of the Miller syndrome patients. In which parent did this recombination occur?

d. Do the number of crossovers you see in Fig. 10.26b fit previous estimates that in the human genome, 1 centiMorgan corresponds to about 1 Mb? Chromosome 16 is about 90 Mb long; chromosome 17 is about 81 Mb long

e. How could researchers use all the sequence data from this family to estimate the per-nucleotide rate of mutation in humans?