Publications by authors named "Matthew T Welling"

5 Publications

  • Page 1 of 1

Recent advances in Cannabis sativa genomics research.

New Phytol 2021 04 8;230(1):73-89. Epub 2021 Jan 8.

La Trobe Institute for Agriculture and Food, Department of Animal, Plant and Soil Sciences, School of Life Sciences, La Trobe University, AgriBio Building, Bundoora, VIC, 3086, Australia.

Cannabis (Cannabis sativa L.) is one of the oldest cultivated plants purported to have unique medicinal properties. However, scientific research of cannabis has been restricted by the Single Convention on Narcotic Drugs of 1961, an international treaty that prohibits the production and supply of narcotic drugs except under license. Legislation governing cannabis cultivation for research, medicinal and even recreational purposes has been relaxed recently in certain jurisdictions. As a result, there is now potential to accelerate cultivar development of this multi-use and potentially medically useful plant species by application of modern genomics technologies. Whilst genomics has been pivotal to our understanding of the basic biology and molecular mechanisms controlling key traits in several crop species, much work is needed for cannabis. In this review we provide a comprehensive summary of key cannabis genomics resources and their applications. We also discuss prospective applications of existing and emerging genomics technologies for accelerating the genetic improvement of cannabis.
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http://dx.doi.org/10.1111/nph.17140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986631PMC
April 2021

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

Sci Rep 2020 10 29;10(1):18643. Epub 2020 Oct 29.

Southern Cross Plant Science, Southern Cross University, Lismore, NSW, 2480, Australia.

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.
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http://dx.doi.org/10.1038/s41598-020-75271-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596533PMC
October 2020

Complex Patterns of Cannabinoid Alkyl Side-Chain Inheritance in Cannabis.

Sci Rep 2019 08 6;9(1):11421. Epub 2019 Aug 6.

Southern Cross Plant Science, Southern Cross University, Lismore, New South Wales, 2480, Australia.

The cannabinoid alkyl side-chain represents an important pharmacophore, where genetic targeting of alkyl homologs has the potential to provide enhanced forms of Cannabis for biopharmaceutical manufacture. Delta(9)-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) synthase genes govern dicyclic (CBDA) and tricyclic (THCA) cannabinoid composition. However, the inheritance of alkyl side-chain length has not been resolved, and few studies have investigated the contributions and interactions between cannabinoid synthesis pathway loci. To examine the inheritance of chemical phenotype (chemotype), THCAS and CBDAS genotypes were scored and alkyl cannabinoid segregation analysed in 210 F progeny derived from a cross between two Cannabis chemotypes divergent for alkyl and cyclic cannabinoids. Inheritance patterns of F progeny were non-Gaussian and deviated from Mendelian expectations. However, discrete alkyl cannabinoid segregation patterns consistent with digenic as well as epistatic modes of inheritance were observed among F THCAS and CBDAS genotypes. These results suggest linkage between cannabinoid pathway loci and highlight the need for further detailed characterisation of cannabinoid inheritance to facilitate metabolic engineering of chemically elite germplasm.
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http://dx.doi.org/10.1038/s41598-019-47812-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684623PMC
August 2019

Developmental Plasticity of the Major Alkyl Cannabinoid Chemotypes in a Diverse Genetic Resource Collection.

Front Plant Sci 2018 23;9:1510. Epub 2018 Oct 23.

Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia.

is a chemically diverse domesticated plant genus which produces a unique class of biologically active secondary metabolites referred to as cannabinoids. The affinity and selectivity of cannabinoids to targets of the human endocannabinoid system depend on alkyl side chain length, and these structural-activity relationships can be utilized for the development of novel therapeutics. Accurate early screening of germplasm has the potential to accelerate selection of chemical phenotypes (chemotypes) for pharmacological exploitation. However, limited attempts have been made to characterize the plasticity of alkyl cannabinoid composition in different plant tissues and throughout development. A chemotypic diversity panel comprised of 99 individuals from 20 populations sourced from the Ecofibre Global Germplasm Collection (ecofibre.com.au and anandahemp.com) was used to examine alkyl cannabinoid variation across vegetative, flowering and maturation stages. A wide range of di-/tri-cyclic as well as C-/C-alkyl cannabinoid composition was observed between plants. Chemotype at the vegetative and flowering stages was found to be predictive of chemotype at maturation, indicating a low level of plasticity in cannabinoid composition. Chemometric cluster analysis based on composition data from all three developmental stages categorized alkyl cannabinoid chemotypes into three classes. Our results suggest that more extensive chemical and genetic characterization of the genepool could facilitate the metabolic engineering of alkyl cannabinoid chemotypes.
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http://dx.doi.org/10.3389/fpls.2018.01510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206272PMC
October 2018

A Belated Green Revolution for Cannabis: Virtual Genetic Resources to Fast-Track Cultivar Development.

Front Plant Sci 2016 29;7:1113. Epub 2016 Jul 29.

Southern Cross Plant Science, Southern Cross University Lismore, NSW, Australia.

Cannabis is a predominantly diecious phenotypically diverse domesticated genus with few if any extant natural populations. International narcotics conventions and associated legislation have constrained the establishment, characterization, and use of Cannabis genetic resource collections. This has resulted in the underutilization of genepool variability in cultivar development and has limited the inclusion of secondary genepools associated with genetic improvement strategies of the Green Revolution. The structured screening of ex situ germplasm and the exploitation of locally-adapted intraspecific traits is expected to facilitate the genetic improvement of Cannabis. However, limited attempts have been made to establish the full extent of genetic resources available for pre-breeding. We present a thorough critical review of Cannabis ex situ genetic resources, and discuss recommendations for conservation, pre-breeding characterization, and genetic analysis that will underpin future cultivar development. We consider East Asian germplasm to be a priority for conservation based on the prolonged historical cultivation of Cannabis in this region over a range of latitudes, along with the apparent high levels of genetic diversity and relatively low representation in published genetic resource collections. Seed cryopreservation could improve conservation by reducing hybridization and genetic drift that may occur during Cannabis germplasm regeneration. Given the unique legal status of Cannabis, we propose the establishment of a global virtual core collection based on the collation of consistent and comprehensive provenance meta-data and the adoption of high-throughput DNA sequencing technologies. This would enable representative core collections to be used for systematic phenotyping, and so underpin breeding strategies for the genetic improvement of Cannabis.
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http://dx.doi.org/10.3389/fpls.2016.01113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965456PMC
August 2016