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

Abstract 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 si...

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Autores principales:	Matthew T. Welling, Lei Liu, Tobias Kretzschmar, Ramil Mauleon, Omid Ansari, Graham J. King
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a5f1ade75bb4179b9bad59d7e7e3596
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spelling	oai:doaj.org-article:0a5f1ade75bb4179b9bad59d7e7e35962021-12-02T15:09:32ZAn extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis10.1038/s41598-020-75271-72045-2322https://doaj.org/article/0a5f1ade75bb4179b9bad59d7e7e35962020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-75271-7https://doaj.org/toc/2045-2322Abstract 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.Matthew T. WellingLei LiuTobias KretzschmarRamil MauleonOmid AnsariGraham J. KingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew T. Welling Lei Liu Tobias Kretzschmar Ramil Mauleon Omid Ansari Graham J. King An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis
description	Abstract 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.
format	article
author	Matthew T. Welling Lei Liu Tobias Kretzschmar Ramil Mauleon Omid Ansari Graham J. King
author_facet	Matthew T. Welling Lei Liu Tobias Kretzschmar Ramil Mauleon Omid Ansari Graham J. King
author_sort	Matthew T. Welling
title	An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis
title_short	An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis
title_full	An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis
title_fullStr	An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis
title_full_unstemmed	An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis
title_sort	extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in cannabis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0a5f1ade75bb4179b9bad59d7e7e3596
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An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis

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