Human Heredity 10th Edition by Michael Cummings

Exercise 2

Sean and Michelle's daughter Molly, age 6, suffered from recurring bacterial lung infections from the time she was 18 months old. Although Molly did not have any of the other usual symptoms, her pediatrician recommended that she be tested for cystic fibrosis (CF), a genetic disorder that affects the glands that produce mucus, digestive enzymes, and sweat. Many individuals with CF develop obstructive lung diseases and infections that can lead to premature death. CF is common among northern Europeans and those with ancestral origins in that region. Both Sean and Michelle were of Irish ancestry, and in the United States, CF occurs in about 1 in 2,300 births among those of northern European ancestry.
Because the defect in CF impairs transport of chloride (a component of salt), a test that measures salt concentration in sweat is used to diagnose this disorder. Molly and her parents went to a nearby Cystic Fibrosis Care Center to have her tested. The results of her sweat test were borderline, so the clinicians at the center asked to take a blood sample to directly test Molly's DNA for mutations in the CF gene. There are over 1,900 different mutations known in this gene, and although tests do not cover all possible mutations, they do check for up to 20 of the most common mutations. One mutation, F508, is present in about 70% of all those with CF. Most other mutations are present in only a small percentage of cases, and some are present only in one family. Molly was found to have mutations in both copies of her CF gene. One copy carried the F508 mutation, and the other copy carried a mutation called G551D. Testing of the parents showed that Sean carried the F508 mutation and Michelle carried the G551D mutation.
The counselors at the center explained that children with two copies of the F508 mutation usually have severe symptoms, because the protein produced by the CF gene does not fold properly in the membrane systems within the cell and is destroyed. Those with one copy of F508 and one copy of the G551D mutation have milder symptoms, because the protein made by the G551D allele is not destroyed and is partially functional. Treatment for CF depends on the range of symptoms present and, to a certain extent, on the types of mutation present. In most cases, therapy involves clearing the lungs and airways of the thick CF mucus, using antibiotics in aerosol form to fight lung infections, as well as maintaining a proper diet.
At the CF Care Center, Sean and Michelle learned that in 2012, the U.S. Food and Drug Administration approved a new drug to treat CF in those who carry the G551D mutation and are at least 6 years old. This drug, called Kalydeco, is the first to directly treat the underlying cause of CF and not just treat symptoms. In those with the G551D mutation, the protein encoded by the CF moves to the membrane surrounding the cell but acts as a partially closed gate, reducing the flow of chloride from inside the cell. Kalydeco works by opening the gate, increasing the flow of chloride, which in turn helps thin out the thick mucus associated with CF. This breakthrough drug was developed using knowledge of how the protein encoded by the CF gene moves through the cell, where it moves to, and how it works, emphasizing the close relationship between genetic disorders and cell structure and function.
Molly began treatments with the drug, uses aerosol antibiotics to help fight lung infections, and is now leading a normal life.
What are the chances that another child will inherit the G551D mutation