Is there a gene for oversimplistic analysis?

Earlier today I had the privilege of attending* the annual Sluckin Memorial Lecture given by eminent Oxford neuroscientist and academic blogger Professor Dorothy Bishop. Dorothy’s theme was ‘Developmental dyslexia and other neurodevelopmental disorders: Distinct syndromes or part of normal variation?‘. There was much in the talk worthy of blogging here, but since I’ve got a stack of final year dissertations to mark I will, for the moment, limit myself to reflections on one point that she raised.

Slide 19 in a presentation by Dorothy Bishop available on Slideshare

Slide 19 in a presentation by Dorothy Bishop available on Slideshare (click image for link)

As with many conditions in the genomic era, there is a desire to find the underlying genetic ’cause’ for dyslexia. This search is not without justification. For example, classic comparison of monozygotic twins (“identical” twins, i.e. same genetics, notwithstanding any epigenetic influences) and dizygotic twins (“non-identical twins”, no more genetically related than any brother or sister) strongly implies that there is a genetic component to dyslexia.

There is stronger evidence than this, particularly for a correlation between dyslexia and the catchily name gene DCDC2. A 2005 paper in the Proceedings of the National Academy of Science, a “Premier League” academic journal, showed a link between specific mutations in this gene and reading disability. A subsequent paper by Tom Scerri and colleagues (including Dorothy) found that a particular Single Nucleotide Polymorphism (a SNP, i.e. a particular base change difference in the DCDC2 gene) was associated with 31% of dyslexics. It was also found in 23% of the control (i.e. non-dyslexic) group, but nevertheless the difference the two is statistically significant (p = 0.005). Continue reading

When the sum is better than the parts: combining the power of comparative genomics and experiments on model organisms

I have been doing some reading for a while now on the ethics of research involving model organisms, particularly the potential for studies on lower species to offer insights into human disease (and thereby contribute to the 3Rs). Some of my musings on the topic can be found here.

Aware of this interest, a colleague recommended that I read a 2004 paper published in the journal Cell. I am very grateful that he did, since the study really has the “wow” factor – demonstrating beautifully the potential of comparative genomics, experiments on model organisms and knowledge of human disease to work together to produce new insights that would have been much harder if any one component was missing. The paper is Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene by Li JB et al. The following notes are my attempt to summarise the best bits.

The importance of cilia and basal bodies in disease
The role of cilia in respiration (and the detrimental effects of smoking on their function) were features of the school biology curriculum when I was a child. However, research over the last ten years or so has demonstrated that cilia have surprisingly diverse roles in development, from determination of left-right symmetry in the body, through to formation and function of specific organs such as the kidneys (for more detail see the Wikipedia entry on Ciliopathy or, if you have access permissions,  Badano et al (2006), The ciliopathies: an emerging class of human genetic disorders Annual Review of Genomics and Human Genetics 7:125-148). Bardet-Biedl syndrome (BBS) is one disorder associated with non-functional or malfunctional cilia. The clinical features can be varied, but include obesity, mental retardation, progressive-onset blindness and polydactylism (i.e. possession of extra digits). Continue reading

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