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Posts Tagged ‘Neurodevelopmental’

A look inside brains that carry (my) genetic risk for autism

Posted in Cerebellum, CNTNAP2, Frontal cortex, Frontal pole, Fusiform gyrus, Rostral fronto-occipital fasciculus, Thalamus, White matter, tagged , , , , , , , , , , , , , , , , , on March 5, 2010| Leave a Comment »

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The A-to-T SNP rs7794745 in the CNTNAP2 gene was found to be associated with increased risk of autism (see Arking et al., 2008).  Specifically, the TT genotype, found in about 15% of individuals, increases these folks’ risk by about 1.2-1.7-fold.  Sure enough, when I checked my 23andMe profile, I found that I’m one of these TT risk-bearing individuals.  Interesting, although not alarming since me and my kids are beyond the age where one typically worries about autism.  Still, one can wonder if such a risk factor might have exerted some influence on the development of my brain?

The recent paper by Tan et al., “Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2” [doi:10.1016/j.neuroimage.2010.02.018 ] suggests there may be subtle, but still profound influences of the TT genotype on brain development in healthy individuals.  According to the authors, “homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation.”

The FA (fractional anisotropy – a measurement of white-matter or myelination) results are consistent with a role of CNTNAP2 in the establishment of synaptic contacts and other cell-cell contacts especially at Nodes of Ranvier – which are critical for proper function of white-matter tracts that support rapid, long-range neural transmission.  Indeed, more severe mutations in CNTNAP2  have been associated with cortical dysplasia and focal epilepsy (Strauss et al., 2006).

Subtle changes perhaps influencing long-range information flow in my brain – wow!

More on CNTNAP2 … its evolutionary history and role in language development.

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Reciprocal genetics of autism vs. schizophrenia

Posted in Chromosome structural variants, Intronic or repetitive sequences, tagged , , , , , , , , on December 7, 2009| 1 Comment »

The recent paper, “Comparative genomics of autism and schizophrenia” by Bernard Crespi and colleagues provides a very exciting take on how genetic data can be mined to understand cognitive development and mental illness.  Looking at genetic association data for autism and schizophrenia, the authors point out that 4 loci are associated with both schizophrenia and autism – however, with a particular twist.  In the case of 1q21.1 and 22q11.21 it seems that genetic deletions are associated with schizophrenia while duplications at this locus are associated with autism.  At 16p11.2 and 22q13.3  it seems that duplications are associated with schizophrenia and deletions are associated with autism.  Thus both loci contain genes that regulate brain development such that too much (duplication) or too little (deletion) of these genes can cause brain development to go awry.  The authors point to genes involved in cellular and synaptic growth for which loss-of-function in growth inhibition genes (which would cause overgrowth) have been associated with autism while loss-of-function in growth promoting genes (which would cause undergrowth) have been associated with schizophrenia.  Certainly there is much evidence for overproduction of synapses in the autism-spectrum disorders and loss of synapses in schizophrenia.  Crespi et al., [doi:10.1073/pnas.0906080106]

Other research covered (here, here) demonstrates the importance of the proper balance of excitatory and inhibitory signalling during cortical development.

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