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Natural Products


which works like a giant microscope that can liter- ally ‘see’ DNA synthesis in real time, enables researchers to assemble highly contiguous and accurate megabase-size stretches, or contigs, of plant genomes. These ‘long reads’ capture unde- tected structural variations, fully intact genes and regulatory regions embedded in complex structures that fragmented draft genomes often miss. Most genome-wide knowledge is obtained at the


level of gene expression (ie, variations in mRNA quantity). It is often assumed that each individual gene transcribes identical RNA molecules. But in reality, one gene may produce several different iso- forms by the use of alternative promoters, exons and terminators. During transcription, alternative RNA molecules (ie, isoforms) are often produced. They can vary in length and differ markedly in function and expression pattern. Alternatively, spliced multiple transcript isoforms can dramati- cally increase the protein-coding potential of the genome. And spliced isoforms transcribed from the same gene can have significantly different and even antagonistic effects. As such, accurately capturing isoform activity


Drug Discovery World Spring 2019


can be crucial to understanding gene structure, reg- ulatory elements and coding regions. And covering the entire length of cDNA sequences and tran- scripts can even enable the discovery of new genes. Enter the isoform sequence (Iso-Seq) method,


which uses long-read technology and requires no assembly, making it an increasingly popular tool – especially in the absence of reference genomes, which is a reality for many researchers working on non-model organisms and plants with genomes that are large and complex.


Marijuana mysteries Despite its growing popularity for medicinal, food, industrial and recreational use, much remains unknown about the genetics of Cannabis sativa, the plant responsible for both marijuana and hemp. The first genome assembly was attempted in 2011 using short read sequencing, but was highly fragmented and incomplete. Several other itera- tions were done over the years and the original team recently released a much-improved genome1, assembled using SMRT Sequencing technology. Another team from the University of Toronto and


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Cannabis sativa, the plant responsible for both marijuana and hemp, has been hard to study, until now. Cannabis is expected to have a significant economic impact of at least $600 billion in pain management and anaesthetics, epilepsy, Alzheimer’s and a wide array of neurological diseases


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