Parental Influence on Human Germline De Novo Mutations in 1,548 Trios From Iceland

Link to Paper

Abstract

• Investigating how de-novo-mutation (DNM) is influenced by parents’ age and sex.
• ~1500 Icelanders, their parents, and children of ~200 Icelanders
• 35x genome-wide coverage
• ~100k DNM found, SNPs and indels, origin found for ~43k

• DNM rates

  • Mothers = 0.37 / year of age
  • Fathers = 1.51 / year of age
• Clustered mutations - higher in mothers
• Genomic span of DNM - larger in mothers

• DNM types

  • mothers
  • change as moms get older
  • decrease 0.26% CpG>TpG / year
  • increase 0.33% C>G / year

  • focused on few regions

    • 20 mb Chr8p
    • C>G mutation rate 50x than normal
    • build-up of non-crossover gene conversion

• Mutations

  • ongoing for thousands of years
  • increased sequence diversity
  • linkage disequilibrium of C>G variants
  • excess C>G shared by chimps, a bit by gorillas, none by orangutans
  • Sequence diversity in humans is a product of ongoing influences of mutation type, genomic location, age and sex.

Glossary

1. DNM = De-Novo Mutations
2. SNP = Single Nucleotide Polymorphism
3. CpG = Cytosine-phosphate-Guanine
4. TpG = Thymine-phosphate-Guanine