Mutation Rate

The appearance of rare dominant genetic diseases, such as retinoblastoma, have been used to estimate the mutation rate in the human population. Retinoblastoma is a childhood cancer of the eye and was a lethal condition until recently. Hence almost every case represented a new mutation (because individuals with the condition did not survive to reproduce and pass the genetic propensity for the disease along to their offspring), and the mutation rate could thus be readily estimated. Modern methods indicate that the mutation rate is roughly one mutation per 10,000 genes per generation. With at least 30,000 genes, this means that each person harbors about three new mutations, although this estimate may be off by a factor of ten. There are many more mutations in non-coding portions of DNA, but these are fairly difficult to study because they have no effect on the phenotype of the person.

About 90 percent of human mutations arise in the father rather than the mother. This may be related to the difference in the number of cell divisions required to produce a sperm versus an egg; sperm are produced late in a male's development, compared to eggs, which are produced quite early in the development of a female. Older parents pass on more mutations, and these may be either mutations within a gene or chromosomal aberrations, which are deletions or rearrangements of the chromosomes and involve many genes. Human mutation rates are generally quite similar worldwide. The exception is in local populations that have been exposed to radioactivity from nuclear testing or other sources.