Recent advances in dyslexia genetics; Animal models of dyslexia;

 Recent advances in dyslexia genetics; Animal models of dyslexia;

Day 1of the Oxford –Kobe symposium on the neurobiological basis of Dyslexia in Alphabetic, Syllabic and Logographic Scripts.

I said that I would try and prepare précis of what was presented at the symposium. That will be a hard task and will be my version of an abstract. I hope people will comment or suggest different perspectives if they do not seem to be correct or they have a different perspective

I will also give a summary of my thoughts at the conclusion of my ‘abstracts’

The presentations   11^th April. Today Thursday

( Only managed two of the eleven today, so far!)

Silvia Paracchini….Recent advances in dyslexia genetics.

There are major difficulties in investigating this area

Summarised as....

No precise biological markers. 

Cross linguistic heterogeneity

Huge time demands on collecting the data.

The very small predicted effect sizes and hence high sample sizes needed.

The complexity of the phenotype.

The heterogeneity of the ‘phenotypes’ creates a major problem for sample set size even if you start with a ‘large population.’

So the ongoing task is to recruit information from as large a population as possible.

They do actually identify a large population of genes that look a bit ‘guilty’ but each gene seems to be responsible/associated with a wide range of disorders.

One such study is extracting data from the Alspac project. http://www.bristol.ac.uk/alspac/. A study of children born in the 90’s. There is a problem though with the definition of dyslexia and the (?) link with IQ.  So an arbitrary decision is only to consider those who ‘are dyslexic with an IQ greater than 85.  The issue of what IQ is and whether it is dependent on whatever Dyslexia is a point that ought to be discussed.

Another area is the consideration of; Handedness and its genetic origin; especially since it seems to have entered the ‘orthodoxy’ of causation/association in dyslexia. But there appears still to be NO evidence of a genetic link or a co morbid link.

The reference is http://hmg.oxfordjournals.org/content/early/2010/11/03/hmg.ddq475  LH is more common in non-dyslexic people.

I actually think that it is more likely that a LH person in a RH world, will simply be more clumsy, and suffer some negative self-image problems at best that will affect academic a performance and behaviour le3ading to more likely being put forward for ‘labelling’!.

Oh dear what about cross dominance!

There appears to be co-morbidity between levels of ‘IQ’ and dyslexia in terms of associated genes. So should we really consider IQ in defining dyslexia?

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Glenn Rosen….Animal Models of developmental dyslexia, anatomy behaviour and genetics.

This was really about the patterns of migration of neurones into the cortical regions of the brain of dyslexic people

There appears to be issues of auditory discrimination in ‘dyslexic people’ when they have ectopic neurone migrations.

There appears to be genetic evidence which supports this have a real biological basis.

Questions to answer…

Could you mimic this in a mouse?

Were there comparable effects on response or learning behaviour in dyslexic adults and ‘modified mice’?

They used specific strains of mice and create ‘ectopias on either the left or right side.

The next stage was to look at reward based learning in response to rapid tone exposure of different patterns. (Associated with magnocellular processing?).

The non-modified mice noticed/ responded to rapid tonal change.  The modified mice did not.

The cell migrations were induced in prenatal mice foetuses.

You could not do this ethically with humans!

Two techniques used.

One introduced phosphorescent plasmids to stem cells in the developing brain to ‘add a genetic component to ‘light up cell migrations’…  This appears to be supportive of the concept.

Another approach was to introduce genes as plasmids into mouse stem cells to knock out a particular gene.   The NMDA receptors   http://www.ncbi.nlm.nih.gov/books/NBK5287/ were used.   Suppression of synaptic activity.

This was a look at the possible use of therapeutic interventions.

This did not affect cell migration but simply slowed sown the learning process.

It was thought it would disrupt the development of left right cranial asymmetry but this does not appear to be moderated by a single gene... (We need to look at gene ecology I think)

It did disrupt microtubule formation and hence cilium development. This might be significant somewhere... As a wicked thought I started at this point to think about the cilial structure of a cone cell!)

Sorry end of evening!! More tomorrow!