Page 25 - PCC08

Studying the generation of de novo mutations taking into account the fundamental differences in male and female gametogenesis
Before birth
Oogenesis
Spermatogenesis (mutagenic replications)
Reproductive period
Fertilization
Mothers: ~22 genome replications
Young Fathers: ~100 genome replications
Old Fathers: ~1,000 genome replications
Can we study mutational footprints of male and female germline?
Figure adapted from Campbell et al. 2014
What is needed to answer this question?
A dataset of de novo mutations (DNMs) that is:
• Whole genome sequencing data • Sequenced deeply enough
• Very large
Inova Preterm Birth Study
‐> detect DNMs genome‐wide ‐> reliable DNM detection
‐> obtain significant answers
• WGS on 832 parent‐offspring trios at 60x coverage!!! • 35,793 putative de novo mutations identified
Need to identify parent of origin of mutated allele (“phase”)
Page 19 of 102
PRECONGRESS COURSE 08 I BARCELONA, SPAIN – 1 JULY 2018 25