Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing

Science. 2012 Dec 21;338(6114):1627-30. doi: 10.1126/science.1229112.


Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. We sequenced 99 sperm from an Asian male by using the newly developed amplification method-multiple annealing and looping-based amplification cycles-to phase the personal genome and map recombination events at high resolution, which are nonuniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Chromosome Segregation
  • Chromosomes, Human / genetics
  • Crossing Over, Genetic
  • Genome, Human*
  • Haplotypes
  • Heterozygote
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Meiosis*
  • Middle Aged
  • Nucleic Acid Amplification Techniques*
  • Recombination, Genetic*
  • Sequence Analysis, DNA / methods*
  • Single-Cell Analysis
  • Spermatozoa / physiology*
  • Transcription Initiation Site