Recent research papers

This research studied how changes in non-coding DNA can cause eye disorders by disrupting molecular switches. 

We focused on a gene called MAB21L2, which is already known to be involved in eye development. We found two families with different changes affecting this gene, one with a missense variant in MAB21L2 (this means one letter in the DNA code was changed, leading to a slightly different protein being made) and the other family had a large deletion of DNA upstream of the MAB21L2 gene. This deletion removed important sections of DNA that control when and where the gene is switched on.

Using zebrafish and frog models, we showed that both types of changes caused similar eye defects, including microphthalmia (small eyes) and coloboma (a gap in the eye's structure). The team also identified specific DNA regions within the deletion that are switches responsible for controlling MAB21L2 activity. One of these regions binds to a protein called Otx2, which is essential for eye development. Disrupting this binding site in frogs also caused eye defects (see figure aober where the right half of the figure shows colobomas in viii, ix, x and xi and a misshapen lens in xii of the affected 'CE14 crispants' frog. 

This research highlights that changes in non-coding DNA (representing switches outside the gene itself) can have a major impact on eye development, and these changes should be considered when diagnosing and understanding genetic eye disorders.

This research paper describes the identification of seven individuals with rare genetic variants in the FBXW11 gene, all of whom have a range of developmental issues. These variants were found through whole exome or whole genome sequencing. FBXW11 is an important gene involved in many developmental processes, including those involving the brain, eye, digits, and jaw.

We studied the effects of these FBXW11 variants using a variety of methods, including:

• Computer modelling to predict the impact of the variants on protein structure and function
• Studying the expression of FBXW11 in developing human and zebrafish embryos to see where the gene is active
• Experiments in zebrafish to see how disrupting the function of the FBXW11 gene affects development

Results suggest these variants disrupt the function of the FBXW11 protein, similar to the observed developmental differences in our patients.

The study concludes that FBXW11 is an important gene for human development and that variants in this gene can cause a range of developmental findings in humans. The authors suggest further research is needed to understand how FBXW11 variants contribute to these disorders and to develop potential treatments.

This research paper describes the identification of seven individuals with rare genetic variants in the FBXW11 gene, all of whom have a range of developmental issues. These variants were found through whole exome or whole genome sequencing. FBXW11 is an important gene involved in many developmental processes, including those involving the brain, eye, digits, and jaw.

We studied the effects of these FBXW11 variants using a variety of methods, including:

• Computer modelling to predict the impact of the variants on protein structure and function
• Studying the expression of FBXW11 in developing human and zebrafish embryos to see where the gene is active
• Experiments in zebrafish to see how disrupting the function of the FBXW11 gene affects development

Results suggest these variants disrupt the function of the FBXW11 protein, similar to the observed developmental differences in our patients.

The study concludes that FBXW11 is an important gene for human development and that variants in this gene can cause a range of developmental findings in humans. The authors suggest further research is needed to understand how FBXW11 variants contribute to these disorders and to develop potential treatments.