A meta-analysis, led by Dr. Hakon Hakonarson of the Childrens’ Hospital of Philadelphia, and involving researchers at UCLA, University of Pennsylvania and other institutions, has found several genetic differences that are more prevalent in people of European descent with Autistic Spectrum Disorder (ASD).
The meta-analysis looked at gene sequence data from their own study and three other studies, to see if any Single Nucleotide Polymorphisms were more common in people with ASD than in non-autistic people. They found that 6 different SNPs at a particular locus were somewhat associated with ASD. These SNPs were at 5p14.1: On a g-stained set of human chromosomes, it is on chromosome 5, on the short arm, in the 14th band from the centromere, in the first sub-band of that band. Several other loci had SNPs that showed association, but not as strongly.
Well, that’s all well and good, but so what? Maybe this is just statistical noise. If that region of the genome has no coding or regulatory function, then it doesn’t matter what variants in sequence exist.
Here’s the good part. The 5p14.1 locus is between 2 genes, CDH10 and CDH9, which code for the proteins cadherin-10 and cadherin-9 respectively. These proteins are involved in regulating cell-cell adhesion, for example, the formation of inter-neuronal connections in the brain. What’s more, the locus contains one of the most highly-conserved regions in the human genome. Now it’s very likely that a highly conserved, non-coding region is a regulatory element involved in development or transcription. What this means is that the SNPs found in this area may induce variations in the expression of cadherin-10 (which is downstream of the locus).
In studies of cadherin-10 expression in the developed brain, no variation in expression has been found to correlate with ASD. However, the study referenced had only 93 subjects, and this may be too small to detect a difference. In addition, if the difference in expression happens during development, which is possible given the proximity of the SNPs to a highly-conserved gene desert, the study of developed brains would be of little use.
Of course, the associations found by this study were not very strong, but with quite a few different loci that might be associated, it seems that there may be many different genetic variants that can, either alone or in concert, produce the ASD phenotype.
Importantly, this is yet another piece of evience that weakens the already moribund hypothesis that autism is caused by vaccination, a hypothesis already denied by a large number of epidemological stidies.
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