A rare dominant mutation expressed at birth was studied in humans. Records showed that s...

A rare dominant mutation expressed at birth was studied in humans. Records showed that six cases were discovered in 40,000 live births. Family histories revealed that in two cases, the mutation was already present in one of the parents. Calculate the spontaneous mutation rate for this mutation. What are some underlying assumptions that may affect our conclusions? Solution: Only four cases represent a new mutation. Because each live birth represents two gametes, the sample size is from 80,000 meiotic events. The rate is equal to

We have assumed that the mutant gene is fully penetrant and is expressed in each individual bearing it. If it is not fully penetrant, our calculation may be an underestimate because one or more mutations may have gone undetected. We have also assumed that the screening was 100 percent accurate. One or more mutant individuals may have been "missed;' again leading to an underestimate. Finally, we assumed that the viability of the mutant and nonmutant individuals is equivalent and that they survive equally in utero. Therefore, our assumption is that the number of mutant individuals at birth is equal to the number at conception. If this were not true, our calculation would again be an underestimate.