Page 33 - PCC08
P. 33
The human mutation rate can be quantified by trio WGS
30-100 de novo point mutations Sequencing Mutational load increases with paternal age
~85% of point mutations are paternal
Direct estimate of neutral mutation rate: ~ 1.2 x 10-8 per nt/generation
Trio Whole Genome
n = 78 trios
de novo point mutations originate in the male germline
Trio Whole Genome Sequencing
30-100 de novo point mutations (0-1 in the exome)
~85% of point mutations are paternal Mutational load increases with paternal age
(1-2 DNM/paternal year - doubles every ~20 years)
Direct estimate of neutral mutation rate: ~ 1.2 x 10-8 per nt/generation
+
Spermatogenesis & copy-errors hypothesis
n = 78 trios
Selfish selection Paternal-age effect
Page 27 of 102
n = 876 trios
Effect of paternal age on total mutation load:
2 novel point mutations per year Doubles every ~20 years
Nature 2017
PRECONGRESS COURSE 08 I BARCELONA, SPAIN – 1 JULY 2018 33
