New paper from my group and
@giladevrony’s!
nature.com/articles/s41467-0…
Historically we measured new mutations in humans using trio studies (parents and offspring). This taught us that on average new mutations increase in offspring with paternal age.
These trio studies showed that mutations in sperm account for 80% of new mutations in humans! These are responsible for our genetic diversity and many genetic diseases. But these studies measure population averages rather than the rate of mutations in individual men.
To address this, we recalled men who had banked sperm from an average of 19 yrs ago (up to 33 yrs)- to provide a new sperm sample. Applying recent advances in DNA duplex sequencing and whole-genome sequencing to these paired samples, we measured a mutation rate for each man.
Mutational patterns seen by direct sperm sequencing matched incredibly well to prior trio studies. And in two men, we found that mosaicism of embryonic mutations hardly changed in sperm with age, indicating remarkable stability of spermatogonial stem cell pools over decades.
We thank our amazing collaborators and funding from @NICHD_NIH. See also exciting recent preprints by
@R_Rahbari and
@aaronquinlan!