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An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis

journal contribution
posted on 2020-12-02, 02:35 authored by Matthew WellingMatthew Welling, L Liu, T Kretzschmar, R Mauleon, O Ansari, GJ King
© 2020, The Author(s). Cannabis produces a class of isoprenylated resorcinyl polyketides known as cannabinoids, a subset of which are medically important and exclusive to this plant. The cannabinoid alkyl group is a critical structural feature that governs therapeutic activity. Genetic enhancement of the alkyl side-chain could lead to the development of novel chemical phenotypes (chemotypes) for pharmaceutical end-use. However, the genetic determinants underlying in planta variation of cannabinoid alkyl side-chain length remain uncharacterised. Using a diversity panel derived from the Ecofibre Cannabis germplasm collection, an extreme-phenotype genome-wide association study (XP-GWAS) was used to enrich for alkyl cannabinoid polymorphic regions. Resequencing of chemotypically extreme pools revealed a known cannabinoid synthesis pathway locus as well as a series of chemotype-associated genomic regions. One of these regions contained a candidate gene encoding a β-keto acyl carrier protein (ACP) reductase (BKR) putatively associated with polyketide fatty acid starter unit synthesis and alkyl side-chain length. Association analysis revealed twenty-two polymorphic variants spanning the length of this gene, including two nonsynonymous substitutions. The success of this first reported application of XP-GWAS for an obligate outcrossing and highly heterozygote plant genus suggests that this approach may have generic application for other plant species.


The authors would like to acknowledge Ecofibre for generously providing Southern Cross University access to the Ecofibre Global Germplasm Collection, as well as for providing insightful information necessary for the selection of accessions. The authors are also grateful for the material and financial support provided by Ecofibre. Finally, the authors would like to acknowledge Dr. Abdul Baten for providing support with the bioinformatic analysis of bulked DNA samples.


Publication Date



Scientific Reports



Article Number



14p. (p. 1-14)


Springer Nature



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The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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