A comparison of methods to detect recombination hotspots

Abstract

Objective: A number of linkage disequilibrium (LD)-based methods have been developed to describe recombination and infer hotspots. We determine the correspondence between LDMAP and LDhat, and between LDMAP and LDhot by comparison with linkage maps and hotspots that have been verified by sperm typing.

Methods: Regression and variance analyses were used to compare LDMAP and LDhat with linkage maps. The location and intensity of hotspots inferred by LDMAP and LDhot were compared with fifteen verified hotspots.

Results: Despite different methodologies and assumptions, LDMAP, LDhat, and linkage maps are highly concordant. Closer inspection shows that LDMAP corresponds more closely with linkage maps across the genome and on sixteen chromosomes compared with LDhat. LDhot identified fourteen and ten of the verified hotspots using high and low density maps. In comparison, LDMAP identified all fifteen hotspots at high and low density. However, some significant discrepancies between sperm and LD-based recombination rates remain.

Conclusions: Combining information from linkage and LDMAP to construct sex-specific high resolution linkage maps suggests that some of these discrepancies may be due to female recombination while others may relate to the age of hotspots. LDMAP based estimates between approximately 68,000 and approximately 112,000 hotspots in the genome with mean widths less than 4 kb.