Characterizing mutagenic effects of recombination through a sequence-level genetic map

Science. 2019 Jan 25;363(6425):eaau1043. doi: 10.1126/science.aau1043.


Genetic diversity arises from recombination and de novo mutation (DNM). Using a combination of microarray genotype and whole-genome sequence data on parent-child pairs, we identified 4,531,535 crossover recombinations and 200,435 DNMs. The resulting genetic map has a resolution of 682 base pairs. Crossovers exhibit a mutagenic effect, with overrepresentation of DNMs within 1 kilobase of crossovers in males and females. In females, a higher mutation rate is observed up to 40 kilobases from crossovers, particularly for complex crossovers, which increase with maternal age. We identified 35 loci associated with the recombination rate or the location of crossovers, demonstrating extensive genetic control of meiotic recombination, and our results highlight genes linked to the formation of the synaptonemal complex as determinants of crossovers.

MeSH terms

  • Chromosome Mapping
  • Crossing Over, Genetic*
  • DNA Mutational Analysis*
  • Epigenesis, Genetic
  • Female
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Humans
  • Iceland
  • Male
  • Maternal Age
  • Mutation Rate*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Synaptonemal Complex