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Main role of the Germline = Fertility & Transmission of genetic material
species survival = Fidelity (genome integrity) <-> Adaptability (variation) = Evolution
Fine Tuning mutation rates is essential!
Paternal age and genetic disease
dominant disorders and congenital anomalies Autism, schizophrenia, bipolar disorder childhood cancers, leukemia, breast cancer
Prevalence of developmental disorders caused by de novo mutations
1:300
Average estimated risk of spontaneous dominant disorder = 1:300 live births (more than T21/T13/T18) Overall risk of pathogenic DNM doubles between ‘Young’ (20-25 yrs) -1/448  ‘older’ (40-45 yrs) 1/210
Deciphering Developmental Disorders Study, Nature 2017 – WES of 4293 trios
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