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J Invest Dermatol. 2019 Sep;139(9):1848-1853.e1. doi: 10.1016/j.jid.2019.04.013.

Research Techniques Made Simple: Forward Genetic Screening to Uncover Genes Involved in Skin Biology.

Author information

1
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
2
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: Bruce.Beutler@UTSouthwestern.edu.
3
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Department of Internal Medicine, Division of Gastroenterology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: Emre.Turer@UTSouthwestern.edu.

Abstract

The primary goals of modern genetics are to identify disease-causing mutations and to define the functions of genes in biological processes. Two complementary approaches, reverse and forward genetics, can be used to achieve this goal. Reverse genetics is a gene-driven approach that comprises specific gene targeting followed by phenotypic assessment. Conversely, forward genetics is a phenotype-driven approach that involves the phenotypic screening of organisms with randomly induced mutations followed by subsequent identification of the causative mutations (i.e., those responsible for phenotype). In this article, we focus on how forward genetics in mice can be used to explore dermatologic disease. We outline mouse mutagenesis with the chemical N-ethyl-N-nitrosourea and the strategy used to instantaneously identify mutations that are causative of specific phenotypes. Furthermore, we summarize the types of phenotypic screens that can be performed to explore various aspects of dermatologic disease.

PMID:
31445571
PMCID:
PMC6711397
[Available on 2020-09-01]
DOI:
10.1016/j.jid.2019.04.013

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