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New advance in assessing the impact of disease-associated mutation on the function of regulatory elements

A team of researchers led by Professor Wendy Bickmore and Dr Shipra Bhatia have defined a new methodology which enables the activities of two regulatory sequences to be simultaneously visualised and compared in live developing zebrafish embryos: November 2021

Zebrafish - disease-associated mutation on the function of regulatory elements

We have a good understanding of how mutations in protein-coding genes can affect gene function but determining how mutations in the vast stretches of the human non-coding genome contribute to disease remains a huge unmet challenge. In large part this is because assaying the function of the regulatory elements found in the non-coding genome depends on the appropriate biological context that cannot be replicated in cells in culture.

In a study recently published in eLife, Quantitative Spatial and Temporal Assessment of Regulatory element activity in Zebrafish, researchers at the MRC Human Genetics Unit, in collaboration with colleagues at the Centre for Mammalian Synthetic Biology, have described a new method to address this challenge.

Using an animal model system – the zebrafish – the method can assess the impact of human disease-associated mutation on the function of regulatory elements, enabling the activities of two regulatory sequences to be simultaneously visualised and compared in a live developing zebrafish embryo.

This allows for quantitative assessment of the precise time and place in development at which the regulatory elements being compared are active.

The consequences of mutation in the non-coding genome remain largely unexplored due to the limitations on analysing the function of regulatory elements in cell cultures. By using zebrafish embryos as a model, this new method allows us a previously inaccessible view and comparison of regulatory sequences in space and time. This exciting development will bring new potential to our understanding of human genetic diseases.

Professor Wendy BickmoreDirector, MRC Human Genetics Unit
Video: New advance in assessing the impact of disease-associated mutation on the function of regulatory elements
New advance in assessing the impact of disease-associated mutation on the function of regulatory elements

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