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Genome Res. 2019 Jan;29(1):146-156. doi: 10.1101/gr.242594.118. Epub 2018 Nov 8.

A physical and genetic map of Cannabis sativa identifies extensive rearrangements at the THC/CBD acid synthase loci.

Author information

1
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
2
Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
4
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
5
Department of Botany, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
6
CanniMed Therapeutics Incorporated, Saskatoon, Saskatchewan S7K 3J8, Canada.
7
Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
8
Canadian Institute for Advanced Research, Toronto, Ontario M5G 1M1, Canada.
9
Anandia Labs, Vancouver, British Columbia V6T 1Z4, Canada.

Abstract

Cannabis sativa is widely cultivated for medicinal, food, industrial, and recreational use, but much remains unknown regarding its genetics, including the molecular determinants of cannabinoid content. Here, we describe a combined physical and genetic map derived from a cross between the drug-type strain Purple Kush and the hemp variety "Finola." The map reveals that cannabinoid biosynthesis genes are generally unlinked but that aromatic prenyltransferase (AP), which produces the substrate for THCA and CBDA synthases (THCAS and CBDAS), is tightly linked to a known marker for total cannabinoid content. We further identify the gene encoding CBCA synthase (CBCAS) and characterize its catalytic activity, providing insight into how cannabinoid diversity arises in cannabis. THCAS and CBDAS (which determine the drug vs. hemp chemotype) are contained within large (>250 kb) retrotransposon-rich regions that are highly nonhomologous between drug- and hemp-type alleles and are furthermore embedded within ∼40 Mb of minimally recombining repetitive DNA. The chromosome structures are similar to those in grains such as wheat, with recombination focused in gene-rich, repeat-depleted regions near chromosome ends. The physical and genetic map should facilitate further dissection of genetic and molecular mechanisms in this commercially and medically important plant.

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