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 journalArticle

9 Citations (Scopus)

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 1 2018

Fingerprint

Single Nucleotide Polymorphism
cancer
phenotype
loci
neoplasms
phenotypic variation
Neoplasms
genomics
Phenotype
infection
Infection
immune system
heritability
linkage disequilibrium
adhesion
lethal genes
cell adhesion
disequilibrium
genetic background
Information Storage and Retrieval

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

Cite this

Large-effect loci affect survival in Tasmanian devils (Sarcophilus harrisii) infected with a transmissible cancer. / Margres, Mark J.; Jones, Menna E.; Epstein, Brendan; Kerlin, Douglas H.; Comte, Sebastien; Fox, Samantha; Fraik, Alexandra K.; Hendricks, Sarah A.; Huxtable, Stewart; Lachish, Shelly; Lazenby, Billie; O'Rourke, Sean M.; Stahlke, Amanda R.; Wiench, Cody G.; Hamede, Rodrigo; Schönfeld, Barbara; McCallum, Hamish; Miller, Michael R.; Hohenlohe, Paul A.; Storfer, Andrew.

In: Molecular ecology, Vol. 27, No. 21, 01.11.2018, p. 4189-4199.

Research output: Contribution to journalArticle

Margres, MJ, Jones, ME, Epstein, B, Kerlin, DH, Comte, S, Fox, S, Fraik, AK, Hendricks, SA, Huxtable, S, Lachish, S, Lazenby, B, O'Rourke, SM, Stahlke, AR, Wiench, CG, Hamede, R, Schönfeld, B, McCallum, H, Miller, MR, Hohenlohe, PA & Storfer, A 2018, 'Large-effect loci affect survival in Tasmanian devils (Sarcophilus harrisii) infected with a transmissible cancer', Molecular ecology, vol. 27, no. 21, pp. 4189-4199. https://doi.org/10.1111/mec.14853
Margres, Mark J. ; Jones, Menna E. ; Epstein, Brendan ; Kerlin, Douglas H. ; Comte, Sebastien ; Fox, Samantha ; Fraik, Alexandra K. ; Hendricks, Sarah A. ; Huxtable, Stewart ; Lachish, Shelly ; Lazenby, Billie ; O'Rourke, Sean M. ; Stahlke, Amanda R. ; Wiench, Cody G. ; Hamede, Rodrigo ; Schönfeld, Barbara ; McCallum, Hamish ; Miller, Michael R. ; Hohenlohe, Paul A. ; Storfer, Andrew. / Large-effect loci affect survival in Tasmanian devils (Sarcophilus harrisii) infected with a transmissible cancer. In: Molecular ecology. 2018 ; Vol. 27, No. 21. pp. 4189-4199.
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