Moving forward with forward genetics: A summary of the INFRAFRONTIER Forward Genetics Panel Discussion.

Asrar Ali Khan,Michael Raess,Martin Hrabe De Angelis

doi:10.12688/f1000research.25369.1

Abstract

In the last few decades, forward genetics approaches have been extensively used to identify gene function. Essentially, forward genetics is the elucidation of the genetic basis of a specific phenotype by screening a population containing random genomic modifications that alter gene function. These approaches have shed light on some essential gene functions in development and disease and have expanded the realm of understanding for genetic disorders. Due to the availability of efficient mutagenesis methods, phenotyping techniques, reliable validation, comprehensive sequence information and translational potential, mouse models are favored for forward genetics approaches. However, in this post-genomic CRISPR-Cas9 era, the relevance and future of forward genetics was brought into question. With more than 7300 mouse strains archived and close interactions with several leading mouse researchers around the world, INFRAFRONTIER - the European Research Infrastructure for mouse models organised a panel discussion on forward genetics at the International Mammalian Genome Conference 2018 to discuss the future of forward genetics as well as challenges faced by researchers using this approach in the current research environment. The commentary presents an overview of this discussion.

Highlights

Forward genetics is an approach that identifies the genetic basis of a specific phenotype
Human geneticists are realising the importance of mouse models replicating the exact mutation found in human patients whereas previously they heavily relied on sequencing, association studies and reverse genetics to understand complex human diseases
Forward genetic approaches can determine which genetic regulatory networks have pathogenic consequences and employ complex mouse models which would be immensely helpful to human geneticists

Summary

Introduction

Forward genetics is an approach that identifies the genetic basis of a specific phenotype. Her group is widely interested in the development and application of both forward and reverse genetic approaches for understanding the etiology of genome variation and its role in health and disease.

Results

Conclusion