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Akil H, Brenner S, Kandel E, Kendler KS, King MC, Scolnick E, Watson JD, Zoghbi HY. Medicine. The future of psychiatric research: genomes and neural circuits. Science . 2010 Mar 26 ; 327(5973):1580-1. PubMed Abstract

Comments on Paper and Primary News
Comment by:  David J. Porteous, SRF Advisor
Submitted 29 March 2010 Posted 29 March 2010

This Perspective is important, not least because of the collective scientific authority and policy influence of the coauthors. But it will also be controversial and there will be dissenters who will need winning over or convincing.

When the Human Genome Project was first mooted, there were passionate dissenting voices, arguing against such a costly investment, but in hindsight only the most blinkered would deny the all-pervasive and positive impact on biomedical science. Be in no doubt, however, that we have just reached the end of the beginning in terms of genome capacity and impact. Next-generation sequencing will change everything, again. Already, the power of complete genome sequencing in related members of an affected family has been demonstrated for genetic heterogenous conditions, such as Charcot-Marie-Tooth neuropathy (one proband sequenced completely and affected and unaffected relatives tested for all possible causal variants; see Lupski et al., 2010), and Miller syndrome/primary ciliary dyskinesia (one family of...  Read more

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Primary News: Policy Brief: A $2 Billion Proposal for Research in Neuropsychiatric Disease

Comment by:  Michael Owen, SRF Advisor
Submitted 30 March 2010 Posted 30 March 2010

By and large, I agree that this is how the big picture looks.

Regarding the genetics: I disagree that we now know that “private” mutations are responsible for disease in many cases. This is conjecture, since no pathogenic point mutations have yet been identified. Moreover, a number of the rare pathogenic variants that have been identified to date (CNVs) are not private, and I see no reason to suppose that the situation will be different for point mutations. However, I very much agree that the focus is going to have to be on very large samples to get full traction on the genetics. Some people think that as we move to sequencing over the next few years, the focus should shift away from very large samples to studies of families. However, given the findings from linkage, where single families with cast iron linkages are extremely rare, and the huge statistical challenges to identifying association with individually rare variants, the samples required will be just as large as those that will be required to identify common risk variants by GWAS, i.e., tens of thousands. So the...  Read more

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