De Novo Mutation Rate Higher in Children of Older Fathers

Higher rate may affect the risk of certain diseases

De Novo Mutation Rate Higher in Children of Older Fathers

WEDNESDAY, Aug. 22 (HealthDay News) -- Children of older fathers have a higher rate of new mutations, which may affect the risk of diseases such as autism and schizophrenia, according to a study published in the Aug. 23 issue of Nature.

To examine the rate of non-inherited, de novo mutations, Augustine Kong, Ph.D., from deCODE Genetics in Reykjavik, Iceland, and colleagues sequenced the genomes of 78 Icelandic parent-offspring trios, where 44 had offspring with autism spectrum disorder and 21 had offspring with schizophrenia. As a comparison, the genomes of 1,859 other Icelanders were also sequenced.

The researchers found 4,933 de novo mutations, with a de novo mutation rate of 0.000000012 per nucleotide per generation. The age of the father at conception (an average of 29.7 years old) was the dominant factor accounting for the diversity in mutation rate of single nucleotide polymorphisms, which was an increase of about two new mutations per year increase in the father's age. Paternal mutations were estimated to double every 16.5 years, and father's age explained nearly all of the nonrandom variation in de novo mutations.

"With the results here, it is now clear that demographic transitions that affect the age at which males reproduce can also have a considerable effect on the rate of genomic change through mutation," Kong and colleagues conclude. "These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism."

One author is an employee of Illumina Cambridge and the remainder are employees of deCODE Genetics.

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