Posts tagged Chromosome
I have written previously about CNV’s and how de novo CNV’s have been recently shown to correlate with disorders like autism and schizophrenia. I have also been militantly proposing that autism and psychosis are diametrically opposed disorders and have been gladdened to find that recent CNV data support that hypothesis. I reported how 16p11.2 duplications were associated with schizophrenia while micro-deletions at same site associated with autism. I also reported how a larger study which looked at multiple CNVs found the same reciprocal effects on CNV sites for autism and schizophrenia, thus bolstering the hypothesis that these are diametrically opposed.
By now you might be wondering what all this has to do with ADHD? Well, for one, early this year I started expanding my model and started conceptualizing ADHD as opposed to Autism in childhood and ADHD thus as belonging to psychotic spectrum; I mused that perhaps the same genetic vulnerability that leads to ADHD in childhood could lead to the manifestation of psychosis in teenage/adulthood. Its worthwhile noting that both ADHD and Psychosis are highly correlated with creativity.
So I could not stop my exuberance at finding that CNVs at another site 16p13.11 has been implicated in ADHD and the duplications are present in both ADHD and Schizophrenia. Also, as per the same study , ADHD children carry a large number of de novo CNV’s – a pattern similar ro Autism/schizophrenia. Some, for example the Neuroskeptic, have taken the same loci of CNVs to mean that these CNVs just confer a general risk of maladaptation, but I think they are missing the forest for the trees. The pattern points to the diametrical model and how CNvs are one mechanism in which tug-of-wars are played (whether evolutionary variation or parent-offspring or between paternal and maternal genomes).
Let me explain what I mean by tug-of-wars. Say you have a evolutionary trade-off between exploration and exploitation, with one extreme being useful in some extreme environmental niche (say food is abundant) and the other strategy useful in the opposed environmental niche (say food is scare) . The trait that gets stabilized should have a bell cure distribution so that the a species can survive even if environment leans toward one extreme. The way to archive this could be by having distribution of frequency of different alleles; or it can be via CNV mechanism. You may have some gentic loci for exploration and have a single popular gene allele that codes for exploration at that loci and CNVs that cause deletions here will lead to more exploitation while CNVs that are duplications will lead to more exploration. Thus, by CNV mechanism one can have more of good thing or less of a good thing, good depending on context (i.e context says what is ‘good’).
To take the example of 16p13.11 – it seems it is somehow related to mental retardation/ creativity/intelligence. A deletion at this site causes mental retardation/multiple congenital anomalies.=, while duplications have benign effects. I would conjecture that duplications (associated with ADHD and schizophrenia) may actually increase intelligence/ creativity. That woudl fit with the diametrical model and the finding that ADHD kids are more creative nd develop language more readily than autistic kids of same age.
I am pasting the background and findings from the abstract below:
Large, rare chromosomal deletions and duplications known as copy number variants (CNVs) have been implicated in neurodevelopmental disorders similar to attention-deficit hyperactivity disorder (ADHD). We aimed to establish whether burden of CNVs was increased in ADHD, and to investigate whether identified CNVs were enriched for loci previously identified in autism and schizophrenia.
Data for full analyses were available for 366 children with ADHD and 1047 controls. 57 large, rare CNVs were identified in children with ADHD and 78 in controls, showing a significantly increased rate of CNVs in ADHD (0·156 vs 0·075; p=8·9×10?5). This increased rate of CNVs was particularly high in those with intellectual disability (0·424; p=2·0×10?6), although there was also a significant excess in cases with no such disability (0·125, p=0·0077). An excess of chromosome 16p13.11 duplications was noted in the ADHD group (p=0·0008 after correction for multiple testing), a finding that was replicated in the Icelandic sample (p=0·031). CNVs identified in our ADHD cohort were significantly enriched for loci previously reported in both autism (p=0·0095) and schizophrenia (p=0·010).
To some the fact that ADHD had the same loci as both Autism and Schizophrenia may speak against there being a diametrical relation; however the same was claimed when initially it was found that autism and schizophrenia CNVs were at the same loci; only after looking at the nature of CNV’s (whether duplications or deletions) were the researchers able to identify the diametrical nature of the CNV’s
I haven’t read the full paper yet (waiting for someone to send me the paper) and as and when I get my hands on the full paper, I’ll update this blog post with more details.
Williams, N., Zaharieva, I., Martin, A., Langley, K., Mantripragada, K., Fossdal, R., Stefansson, H., Stefansson, K., Magnusson, P., & Gudmundsson, O. (2010). Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis The Lancet DOI: 10.1016/S0140-6736(10)61109-9