Page 43 - PCC08

Implications
Human genome is complex and very heterogeneous
Germline mutation rates are low –> 30-100 new point mutations/generation
 Paternal age-effect and high birth prevalence of PAE disorders = random replication errors + selection of oncogenic mutations over time
 Selfish mosaicism is a universal process – occurring in the testes of all men as they age – oncogenic mutations hijack SSC homeostasis - RAS/MAPK pathway and may involve other pathways
 Direct visualisation of the ‘selfish’ origin of pathogenic mutations in the human testis (“homunculus”)
 Example of ‘selfishness’/genomic conflict: a mutation “beneficial” in the testis is harmful to the organism –
 Impact on genome heterogeneity/complex diseases (ASD/SCZ/Cancer)?
 ?Impact on SSCs if cultured outside of their normal niche?
WIMM (Oxford)
Geoff Maher Eleni Giannoulatou Jasmine Lim Steve Twigg Marie Bernkopf Nils Koelling Simon McGowan (CBRG)
Andrew Wilkie
Statistics/WTCHG (Oxford)
Gil McVean
Oxford Fertility Clinic
Aysha Itani
Karen Turner Oxford OCHRe Clare Verrill Oxford Heart Valve Bank Jill Davies
Vinod Motani
Copenhagen University Hospital (DK)
Ewa Rajpert-DeMeyts
Erasmus MC-Rotterdam University (NL)
Lendeert Looijenga
Thanks to...
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PRECONGRESS COURSE 08 I BARCELONA, SPAIN – 1 JULY 2018 43