Harnessing the power of genetics: fast forward genetics in Caenorhabditis elegans
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REVIEW
Harnessing the power of genetics: fast forward genetics in Caenorhabditis elegans Jogender Singh1 Received: 19 July 2020 / Accepted: 27 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Forward genetics is a powerful tool to unravel molecular mechanisms of diverse biological processes. The success of genetic screens primarily relies on the ease of genetic manipulation of an organism and the availability of a plethora of genetic tools. The roundworm Caenorhabditis elegans has been one of the favorite models for genetic studies due to its hermaphroditic lifestyle, ease of maintenance, and availability of various genetic manipulation tools. The strength of C. elegans genetics is highlighted by the leading role of this organism in the discovery of several conserved biological processes. In this review, the principles and strategies for forward genetics in C. elegans are discussed. Further, the recent advancements that have drastically accelerated the otherwise time-consuming process of mutation identification, making forward genetic screens a method of choice for understanding biological functions, are discussed. The emphasis of the review has been on providing practical and conceptual pointers for designing genetic screens that will identify mutations, specifically disrupting the biological processes of interest. Keywords C. elegans · Forward genetics · Chemical mutagenesis · Suppressor · Single nucleotide polymorphism · Nextgeneration sequencing
Introduction The understanding of different biological processes requires the identification of underlying genes, their activities, and interactions among the products of different genes. Traditionally, to understand the molecular basis of a given biological process, mutant organisms that display variations in the biological process are obtained and studied. The genes that lead to observable traits or phenotype are then determined. This approach of determining the genetic basis of a phenotype is known as forward genetics. Thus, forward genetics is a phenotype-based screening method where random mutagenesis is used to identify genes causing a phenotype of interest. This is in contrast to reverse genetics, a genotypebased screening method where a particular gene is altered, Communicated by Stefan Hohmann. * Jogender Singh [email protected] 1
Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Madhya Pradesh 462066, India
and the associated phenotype is investigated. The existence of natural genetic variation could be exploited to determine the underlying genetic basis of a phenotype. Besides, mutations can be induced by various methods, including chemicals and radiations, to expedite the process of determining the genetic basis of a biological process. The conserved nature of various biological processes makes it feasible to understand complex biological systems by studying simpler organisms. Forward genetic studies in several simple model organisms, including the baker’s yeast Sacch
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