Large-effect loci affect survival in Tasmanian devils (Sarcophilus harrisii) infected with a transmissible cancer

Mark J. Margres, Menna E. Jones, Brendan Epstein, Douglas H. Kerlin, Sebastien Comte, Samantha Fox, Alexandra K. Fraik, Sarah A. Hendricks, Stewart Huxtable, Shelly Lachish, Billie Lazenby, Sean M. O'Rourke, Amanda R. Stahlke, Cody G. Wiench, Rodrigo Hamede, Barbara Schönfeld, Hamish McCallum, Michael R. Miller, Paul A. Hohenlohe, Andrew Storfer

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Identifying the genetic architecture of complex phenotypes is a central goal of modern biology, particularly for disease-related traits. Genome-wide association methods are a classical approach for identifying the genomic basis of variation in disease phenotypes, but such analyses are particularly challenging in natural populations due to sample size difficulties. Extensive mark–recapture data, strong linkage disequilibrium and a lethal transmissible cancer make the Tasmanian devil (Sarcophilus harrisii) an ideal model for such an association study. We used a RAD-capture approach to genotype 624 devils at ~16,000 loci and then used association analyses to assess the heritability of three cancer-related phenotypes: infection case–control (where cases were infected devils and controls were devils that were never infected), age of first infection and survival following infection. The SNP array explained much of the phenotypic variance for female survival (>80%) and female case–control (>61%). We found that a few large-effect SNPs explained much of the variance for female survival (~5 SNPs explained >61% of the total variance), whereas more SNPs (~56) of smaller effect explained less of the variance for female case–control (~23% of the total variance). By contrast, these same SNPs did not account for a significant proportion of phenotypic variance in males, suggesting that the genetic bases of these traits and/or selection differ across sexes. Loci involved with cell adhesion and cell-cycle regulation underlay trait variation, suggesting that the devil immune system is rapidly evolving to recognize and potentially suppress cancer growth through these pathways. Overall, our study provided necessary data for genomics-based conservation and management in Tasmanian devils.

Original languageEnglish (US)
Pages (from-to)4189-4199
Number of pages11
JournalMolecular ecology
Volume27
Issue number21
DOIs
StatePublished - Nov 2018

Bibliographical note

Funding Information:
Save the Tasmanian Devil Appeal – University of Tasmania Foundation; Holsworth Wildlife Research Endowment; National Science Foundation, Grant/Award Number: DEB 1316549; Australian Academy of Science; Australian Research Council, Grant/Award Number: A00000162, FT100100250, LP0561120, DP110102656; Ian Potter Foundation; Tasmanian Government; Commonwealth Government of Australia; Estate of W.V. Scott; Mohammed bin Zayed Conservation Fund; National Geographic Society; NIH, Grant/ Award Number: P30 GM103324

Funding Information:
This work was funded under NSF grant DEB 1316549 as part of the joint NSF-NIH-USDA Ecology and Evolution of Infectious Diseases programme to AS, PAH, MEJ and HM, the Australian Research Council (ARC) Future Fellowship (FT100100250) to MEJ, ARC Large Grants (A00000162) to MEJ, Linkage (LP0561120) to MEJ and HM, and Discovery (DP110102656) to MEJ and HM. Field work was additionally supported by Eric Guiler grants from the Save the Tasmanian Devil Appeal?University of Tasmania Foundation, the Ian Potter Foundation, the Australian Academy of Science, Estate of W.V. Scott, the National Geographic Society, the Mohammed bin Zayed Conservation Fund, the Holsworth Wildlife Trust, the Tasmanian Government and the Commonwealth Government of Australia. Animal use was approved by the IACUC at Washington State University (ASAF#04392), the University of Tasmania Animal Ethics Committee (A0008588, A0010296, A0011696, A0013326, A0015835) and the Department of Primary Industries, Parks, Water and Environment Animal Ethics Committee. Additional support was provided by NIH P30 GM103324.

Funding Information:
This work was funded under NSF grant DEB 1316549 as part of the joint NSF‐NIH‐USDA Ecology and Evolution of Infectious Diseases programme to AS, PAH, MEJ and HM, the Australian Research Council (ARC) Future Fellowship (FT100100250) to MEJ, ARC Large Grants (A00000162) to MEJ, Linkage (LP0561120) to MEJ and HM, and Discovery (DP110102656) to MEJ and HM. Field work was additionally supported by Eric Guiler grants from the Save the Tasmanian Devil Appeal—University of Tasmania Foundation, the Ian Potter Foundation, the Australian Academy of Science, Estate of W.V. Scott, the National Geographic Society, the Mohammed bin Zayed Conservation Fund, the Holsworth Wildlife Trust, the Tasmanian Government and the Commonwealth Government of Australia. Animal use was approved by the IACUC at Washington State University (ASAF#04392), the University of Tasmania Animal Ethics Committee (A0008588, A0010296, A0011696, A0013326, A0015835) and the Department of Primary Industries, Parks, Water and Environment Animal Ethics Committee. Additional support was provided by NIH P30 GM103324.

Publisher Copyright:
© 2018 John Wiley & Sons Ltd

Keywords

  • GWAS
  • adaptation
  • cancer
  • effect size
  • genotype–phenotype

Fingerprint Dive into the research topics of 'Large-effect loci affect survival in Tasmanian devils (Sarcophilus harrisii) infected with a transmissible cancer'. Together they form a unique fingerprint.

Cite this