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New tools help show what genes do

To understand the roles of different genes, Dr James Brown and colleagues at the MRC Harwell Institute are part of a project trying to find out what every single mouse gene does. To help speed things along, they have developed new software to analyse images of mouse embryos.

black mouse
Our 20,000 genes provide the instructions for everything our body does. But we don’t yet know what each one is responsible for. We share 90 percent of our genes with mice so finding out their ‘function’ could help us understand more about human disease. So at the International Mouse Phenotyping Consortium (IMPC) we are going through them one by one.

Dr James Brown headshotTo do this we look to see what changes in a mouse embryo when we switch off one of the genes. This is no mean feat, and is only made possible through a collaboration of hundreds of researchers from over 30 institutions world-wide, all working together to care for and study thousands of mice each year. Together, we generate vast volumes of data that need to be analysed, processed, and made readily accessible to the scientific community.

One in three genes are needed for life

We have already found that around one third of genes are essential for life. Mouse embryos that lack these genes don’t develop properly and do not reach full term. We analyse these embryos, by comparing them with healthy embryos, to work out what is happening at each stage of development. It also gives us clues about the missing gene’s function.

Getting the picture

We use a range of 3D imaging techniques to closely inspect embryos and find defects, both internally and externally. In a project as large scale as the IMPC, manually inspecting these images is difficult and labour intensive.  So we needed to develop software to analyse these images faster and more reliably.

The overlapping mapper

The first piece of software we’ve developed lets us identify defects easily.  First, the embryo images are lined up with a number of healthy embryos so that they overlap. Then the software compares the two groups and produces a map highlighting differences as coloured blobs on the image.

Screenshot from the Volume Phenotype Viewer

Software 1 – Volume Phenotype Viewer: the software shows a 3D image made by using a series of X-rays. Blue and red blobs show where the software has automatically identified abnormal regions.

The comparer

The second piece of software lets you compare and interact with images of embryos in a web browser. You can look at embryos as 2D cross-sections by slicing in different directions. Or you can look at them in 3D, and rotate and zoom in on the images. Have a go yourself on our website. Because you can see the images side-by-side, it’s easy to spot differences between healthy embryos and embryos which are missing a gene.

Screenshot of the Interactive Embryo Viewer

Software 2 – Interactive Embryo Viewer: the software lets you compare images of a healthy embryo (top) and an embryo lacking the gene in question below. This embryo lacks the Svep1 gene. Embryos without Svep1 develop excess fluid and have smaller lungs. Images provided by the Jackson Laboratory.

Building a library

These pieces of software have already helped researchers to extract the functions of multiple genes. And by sharing the images with the scientific community we hope they will lead to the discovery of the functions of many more. Many genes are common to more than one human disease, so these resources could serve as a powerful tool for uncovering the underlying causes of various disorders.

Next steps

So far we’ve analysed 4,293 genes at the IMPC. So just 15,707 to go!

Keep up to date with the IMPC and search genes and phenotypes.

This study was published in Briefings in Bioinformatics.

One Comment Post a comment
  1. John. W Shannonoi #

    I am 100, so I am interested in why.. Thank you, your research is fascinating.John

    November 3, 2016

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