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发帖数: 831 | 1 Rate of de novo mutations and the importance of father’s age to disease
risk
Nature 488, 471–475 (23 August 2012)
Mutations generate sequence diversity and provide a substrate for selection.
The rate of de novo mutations is therefore of major importance to evolution
. Here we conduct a study of genome-wide mutation rates by sequencing the
entire genomes of 78 Icelandic parent–offspring trios at high coverage. We
show that in our samples, with an average father’s age of 29.7, the average
de novo mutation rate is 1.20 × 10−8 per nucleotide per
generation. Most notably, the diversity in mutation rate of single
nucleotide polymorphisms is dominated by the age of the father at conception
of the child. The effect is an increase of about two mutations per year. An
exponential model estimates paternal mutations doubling every 16.5
years. After accounting for random Poisson variation, father’s age is
estimated to explain nearly all of the remaining variation in the de novo
mutation counts. These observations shed light on the importance of the
father’s age on the risk of diseases such as schizophrenia and autism. |
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