Chapter 11, Problem 41P

Table 11.2 and Fig. 11.27 together portray the search for the mutation causing Nic Volker’s severe inflammatory bowel disease. Neither of Nic’s parents had the condition, so geneticists narrowed their investigation by focusing on rare variants that showed a recessive pattern and those on the X chromosome.

a.	For candidate variants on an autosome, would the researchers have looked only for variants for which Nic is homozygous? Explain.
b.	Apart from the recessive and X-linked hypotheses, do any other possible explanations exist for Nic’s condition?
c.	The causative mutation was pinpointed by analyzing only Nic’s exome, because at the time of these investigations, whole-genome or whole-exome sequencing was too expensive to perform on his parents. How could you determine inexpensively whether or not this mutation occurred de novo in the germ line of one of his parents (that is, during the formation of the particular egg or sperm that produced Nic)? Your answer should not involve whole-genome or whole-exome sequencing.