New research finds that scientists are still studying the same 10% of human genes and ignoring the rest, highlighting the importance of international projects such as the IMPC.
Historical bias is a key reason why biomedical researchers continue to study the same 10 percent of all human genes while ignoring many genes known to play roles in disease, according to a study publishing in PLOS Biology. The researchers involved in this study suggest this bias is bolstered by research funding mechanisms and social forces. The International Mouse Phenotyping Consortium (IMPC) aims to address this issue by creating a platform that characterizes all 20,000 protein-coding mouse genes, which can then give valuable information into homologous genes in the human genome.
Recent studies have reported that researchers actively study only about 2,000 human protein-coding genes, so the researchers set out to find why. They compiled 36 distinct resources describing various aspects of biomedical research and analyzed the large database for answers. The team found that well-meaning policy interventions to promote exploratory or innovative research actually result primarily in additional work on the most established research topics — those genes first characterized in the 1980s and 1990s, before completion of the Human Genome Project. The researchers also discovered that postdoctoral fellows and Ph.D. students who focus on poorly characterized genes have a 50 percent lower chance of becoming an independent researcher.
The researchers applied a systems approach to the data — which included chemical, physical, biological, historical and experimental data — to uncover underlying patterns. In addition to explaining why some genes are not studied, they also explain the extent to which an individual gene is studied. And they can do that for approximately 15,000 genes.
The Human Genome Project — the identification and mapping of all human genes, completed in 2003 — promised to expand the scope of scientific study beyond the small group of genes scientists had studied since the 1980s. But the Northwestern researchers found that 30 percent of all genes have never been the focus of a scientific study and less than 10 percent of genes are the subject of more than 90 percent of published papers.
“The bias to study the exact same human genes is very high,” said Amaral, the Erastus Otis Haven Professor of Chemical and Biological Engineering and a co-author of the study. “The entire system is fighting the very purpose of the agencies and scientific knowledge which is to broaden the set of things we study and understand. We need to make a concerted effort to incentivize the study of other genes important to human health.”
The International Mouse Phenotyping Consortium
This new research highlights the need for projects such as the IMPC, in which the aim is to characterize approximately all 20,000 or so protein coding genes. To achieve this, genes in the mouse genome are switched off, or ‘knocked out’, then standardised physiological tests undertaken across a range of biological systems. This data is then made freely available to the research community. As well as completing large scale comparative studies, the overall aim of the project is to create a platform for this data where researchers/clinicians can search for genes or diseases of interest to help them understand human health and disease. Data for over 6,000 genes is now available on the IMPC website and the project should therefore help address some of the main issues outlined above.
“The IMPC is leveling the playing field by freely providing robust phenotype data for poorly characterized genes. Nothing pleases me more than helping researchers overcome these barriers and discover new research areas none of us have dreamed of. This will be lasting legacy of the IMPC and is why our global partners continue to generate and phenotype mutant mice every day.” said Terry Meehan, a member of IMPC, and the Mouse Informatics Coordinator at the European Bioinformatics Institute.
Lluis Montoliu, researcher at the National Center for Biotechnology (CNB-CSIC) and member of the IMPC said “In the scientific community we all know of ‘famous’ genes and genes that are not so. Fashions also prevail in the scientific community and, indeed, there are many very relevant genes that, due to their difficulty and scarce literature, remain largely unknown. For example, huntingtin, whose gene causes Huntington’s deadly neurodegenerative disease. The IMPC aims to generate and phenotype mutant mice for each and every one of the 20,000 genes, whether or not they are famous, in order to correlate the data obtained with their homologous genes in the human genome.”
PLOS Biology research article: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006643
More information on the IMPC: https://www.mousephenotypetest.org/what-is-the-impc/
An article published in the journal Theriogenology demonstrates that it is possible to cryopreserve mouse spermatozoa at −80 °C. What is more, the cryopreserved sperm can be stored at -80 °C for at least one year before being placed in liquid nitrogen for indefinite storage. The team involved in this research have used a simple and efficient method for freezing spermatozoa of wild type and mutant mouse lines on a C57BL/6N background. Mice with this genetic background are used for a variety of projects, including the IMPC. This technique has the potential to transform the sperm storage process, as it simplifies freezing and facilitates storage and transportation.
In particular, this new method will be useful for laboratories with limited access to liquid nitrogen as well as projects that generate mutant lines using CRISPR/Cas9 who want a more accessible −80 °C freezer option. The results of the study also highlight that mouse spermatozoa are extremely robust and can be stored and transported at −80 °C for a significant amount of time without loss of viability.
Below is a recent video that explains how mouse sperm is currently shipped and stored using dry ice, featuring Martin Fray who was one of the authors of this latest development.