gms | German Medical Science

Background: Genetic maps are built based on the relative positioning of genes or genomic markers and are species-specific. The distance between markers can be measured on two scales: physical and genetic. The latter is of more interest to breeders as it is related to the probability that variants at two markers jointly transmit from parent to offspring. This probability is determined by the so-called recombination rate.

Methods: Based on medium-density genotype data from a main German dairy breed, we aim at constructing a combined physical-genetic map by bringing together the physical and genetic measures of the proximity of genomic markers. Exploiting the genetic similarity of paternal half-siblings, recombination rate between marker pairs can be assessed by using an established maximum likelihood approach. Derivation of genetic distances strictly requires a proper ordering of markers on the physical scale. Markers which were putatively misplaced in the current genome assembly were detected by inspecting unusually large estimates of recombination rate between close markers.

We propose to approximate genetic length of each marker interval by a quadratic optimisation approach employing all recombination rates less than 0.05. This procedure was verified using simulated data for which recombination rates were also derived by counting cross-overs between marker pairs; these estimates were used as a baseline. Additionally, results were compared to a deterministic approach for the estimation of recombination rate between adjacent markers. In this case, estimates were directly converted into genetic distances in Morgan units.

Results: A linear relationship between physical and genetic distances has been ascertained which can be explained by the uniform distribution of cross-over events in the simulation study. The optimisation approach led to underestimated genetic distances but bias was less than compared to the deterministic approach. The analysis of empirical data revealed 51 putatively misplaced markers. After removing these candidates, the physical-genetic map followed not only linear but also S-shaped curves for some of the chromosomes, substantiating genomic regions with increased crossing-over frequency (i.e. hotspots).

Conclusions: The analysis of pairwise recombination rates discovered options for further improving the current bovine genome assembly. Modelling cross-over events with non-uniform distribution needs yet to be established to elucidate the influence of hotspots on genetic map distances.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.