Abstract
Most current biomedical and protein research focuses only on a small proportion of genes, which results in a lost opportunity to identify new gene-disease associations and explore new opportunities for therapeutic intervention. The International Mouse Phenotyping Consortium (IMPC) focuses on elucidating gene function at scale for poorly characterized and/or under-studied genes. A key component of the IMPC initiative is the implementation of a broad phenotyping pipeline, which is facilitating the discovery of pleiotropy. Characterizing pleiotropy is essential to identify gene-disease associations, and it is of particular importance when elucidating the genetic causes of syndromic disorders. Here we show how the IMPC is effectively uncovering pleiotropy and how the new mouse models and gene function hypotheses generated by the IMPC are increasing our understanding of the mammalian genome, forming the basis of new research and identifying new gene-disease associations.
Highlights
We still do not have a deep understanding of how mammalian genomes function
Most current genetic research focuses only on a small proportion of genes, many of which have already been studied extensively. This leaves a large amount of the genome under-studied, which results in a lost opportunity to identify disease-associated genes and explore new opportunities for therapeutic intervention (Edwards et al 2011; Oprea et al 2018; Stoeger et al 2018)
Despite pleiotropy’s central importance in biology, empirical datasets have not been available until recently. The analysis of these datasets is contributing to the understanding of pleiotropy, such as its genomic pattern, evolutionary implications, the evaluation of mathematical models and their theoretical predictions and the verification of hypotheses (Wang et al 2010, Wagner and Zhang 2011, Saltz et al 2017; Archambeault et al 2020; Geiler-Samerotte et al 2020; Shikov et al 2020), as well as to identify new gene-disease associations. In this Commentary, we focus on the relevance of pleiotropy for understanding gene function and, in particular, its critical importance to identify gene-disease associations
Summary
We still do not have a deep understanding of how mammalian genomes function. Most current genetic research focuses only on a small proportion of genes, many of which have already been studied extensively. Among the 7590 genes, we distinguish two special cases of genes, those for which the null homozygotes result in a lethal phenotype (lack of homozygous viable individuals) and those genes for which the individuals cannot be associated with any trait (no detectable effect in the knockout line).
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