Inferring genome-wide recombination landscapes from advanced intercross lines: application to yeast crosses

Lichten, M., Illingworth, C. J.R. , Parts, L., Bergström, A., Liti, G. and Mustonen, V. (2013) Inferring genome-wide recombination landscapes from advanced intercross lines: application to yeast crosses. PLoS ONE, 8(5), e62266. (doi: 10.1371/journal.pone.0062266) (PMID:23658715) (PMCID:PMC3642125)

Abstract

Accurate estimates of recombination rates are of great importance for understanding evolution. In an experimental genetic cross, recombination breaks apart and rejoins genetic material, such that the genomes of the resulting isolates are comprised of distinct blocks of differing parental origin. We here describe a method exploiting this fact to infer genome-wide recombination profiles from sequenced isolates from an advanced intercross line (AIL). We verified the accuracy of the method against simulated data. Next, we sequenced 192 isolates from a twelve-generation cross between West African and North American yeast Saccharomyces cerevisiae strains and inferred the underlying recombination landscape at a fine genomic resolution (mean segregating site distance 0.22 kb). Comparison was made with landscapes inferred for a similar cross between four yeast strains, and with a previous single-generation, intra-strain cross (Mancera et al., Nature 2008). Moderate congruence was identified between landscapes (correlation 0.58–0.77 at 5 kb resolution), albeit with variance between mean genome-wide recombination rates. The multiple generations of mating undergone in the AILs gave more precise inference of recombination rates than could be achieved from a single-generation cross, in particular in identifying recombination cold-spots. The recombination landscapes we describe have particular utility; both AILs are part of a resource to study complex yeast traits (see e.g. Parts et al., Genome Res 2011). Our results will enable future applications of this resource to take better account of local linkage structure heterogeneities. Our method has general applicability to other crossing experiments, including a variety of experimental designs.

• Item Type: Articles
• Additional Information: The authors would like to acknowledge the Wellcome Trust for support under grant reference 098051. LP was supported by a fellowship from the Canadian Institute for Advanced Research.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Illingworth, Dr Chris
• Authors: Lichten, M., Illingworth, C. J.R., Parts, L., Bergström, A., Liti, G., and Mustonen, V.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in PLoS One 8(5):e62266
• Publisher Policy: Reproduced under a Creative Commons License