High-Resolution Mapping of Crossovers Reveals Extensive Variation in Fine-Scale Recombination Patterns Among Humans

Recombination plays a crucial role in meiosis, ensuring the proper segregation of chromosomes. Recent linkage disequilibrium (LD) and sperm-typing studies suggest that recombination rates vary tremendously across the human genome, with most events occurring in narrow “hotspots. ” To examine variation in fine-scale recombination patterns among individuals, we used dense, genome-wide single-nucleotide polymorphism data collected in nuclear families to localize crossovers with high spatial resolution. This analysis revealed that overall recombination hotspot usage is similar in males and females, with individual hotspots often active in both sexes. Across the genome, roughly 60 % of crossovers occurred in hotspots inferred from LD studies. Notably, however, we found extensive and heritable variation among both males and females in the proportion of crossovers occurring in these hotspots. Errors in the recombination process during meiosis underlie a variety of chromosomal abnormalities and greatly increase the risk of nondisjunction (1–3). Nonetheless, the total number of recombination events varies significantly among individuals (4), and rates of genetic exchange over fine scales are known to differ in males (5–8). These observations hint at extensive variation in many aspects of the recombination process (9), the nature and extent of which have yet to be systematically characterized. In particular, because observations of recombination between closely linked markers come from sperm typing, we still know little about fine-scale patterns of recombination in females. With the recent advent of high-density genotyping platforms, it is now feasible to study finescale patterns of recombination with pedigree data. To test this approach, we analyzed genomewide single-nucleotide polymorphism data fro