Study highlights variation in human mutation rates

In the first direct measure of new mutation rates in humans, researchers have found that when parents pass their genes to their children an average of 60 mutations are introduced into the genetic code during the process.

The study, published in Nature Genetics online, analysed the complete genetic sequences of two families, consisting of both parents and one child, collected as part of the 1,000 Genomes Project to search for mutations that were present in children, but absent from their parents.

However, the number of mutations discovered was lower than anticipated. Professor Philip Awadalla from the University of Montreal, who co-led the study, said: 'We had previously estimated that parents would contribute an average of 100 to 200 mistakes to their child'. 

The results also suggested considerable variation in mutation rates within and between families. In one family, 92 percent of mutations were derived from the father, whereas in the other only 36 percent came from the father.

Dr Matthew Hurles from the Wellcome Trust Sanger Institute, Cambridge, UK, who also co-led the study, said: 'This is a surprise. Many people expected that in all families most mutations would come from the father, due to the additional number of times that the genome needs to be copied to make sperm, as opposed to an egg'.

Identifying new mutations was technically challenging with just one mutation occurring every 100 million nucleotides. Professor Awadalla said: 'Today, we have been able to test previous theories through new developments in experimental technologies and our analytical algorithms. This has allowed us to find these new mutations, which are like small needles in a very large haystack'.

All previous efforts to determine mutation rates have involved averaging across multiple generations or across female and male mutation rates and provided no information about variation in mutation rates between individuals.

Owing to the small number of individuals in this study, it is difficult to tell whether the variation in mutation rates between families is due to differences in mutation processes or the parents' eggs and sperm. However, these new methods can be used to look at additional families to determine the causes of variation and examine the influence of parental age and environmental exposures on mutation rates.