check for a phenotype. Then we try to rescue the morpholino-induced phenotype by co-injecting the wildtype (WT) humancDNA of the test gene. Finally, we test whether co-injection ofmorpholino and mutated human cDNA can rescue the phenotypein the fish embryos. Using these approaches, we have identifiedseveral new genes associated with these diseases (such asSHANK3, IL1RAPL1, SYNGAP1, STXBP1, and others). Interestingly,some of the identified genes show deleterious de novo mutationsin patients from the 3 disease cohorts, suggesting close biologicaloverlap in these three. A combination of high-throughputsequencing, automated SNP discovery, genetic and biologicalvalidation strategies can be used to identify SCZ and AUT genes.This approach can also be used to identify genes involved in othercommon diseases, especially as next-generation sequencingtechnologies become available to screen a larger number ofcandidate genes in more patient samples. However the challengeremains in robustly linking a DNA variant to a clinical phenotype.Acknowledgements: Genome Canada and Génome Québec, Uni-versité de Montréal and Canadian Foundation for Innovation &CIHR.

doi:10.1016/j.schres.2010.02.112

CLINICAL AND COGNITIVE EXTREME PHENOTYPES AND CNVS INADOLESCENT AND ADULT FUNCTIONAL PSYCHOSIS

Mar Fatjó-VilasUniversity of Barcelona, Spain

Rare but with relatively high penetrance copy number variations(CNVs) have been described in adult and early onset schizophreniabut also in autistic disorders. In this sense, CNVs in genes coding forproteins that interact directly and play a role in synaptic develop-ment and function (NRXN1 and APBA2), have been interestinglyidentified in schizophrenic patients but also in autistic and mentallyretarded patients. The above mentioned results together with theincreasingly acceptance that the imprecision of categorical psychia-tric diagnoses can be a limiting factor in understanding the geneticbasis of mental disorders, suggest the interest of analysing CNVs inearly onset psychosis, including those cases with overlappingfeatures with autism and intelligence disabilities such as low IQ,developmental milestones and poor premorbid adjustment. The aimof the present study was to study the relationship between copynumber genomic variability and extreme clinical and cognitivephenotypes of psychosis. We selected (from a sample of 150 families(quadruplets) with an affected/son daughter for functional psycho-sis) a subgroup of 20 Caucasian male patients with extremephenotypes to perform a comparative genomic hybridization(CGH) analysis. Patients were selected according to their age atonset (age of first symptoms range: 13-30 years; assessed with theSymptom Onset in Schizophrenia Inventory), Intelligence Quotient(IQ range: 55-120; assessed with WISC/WAIS) and premorbidadjustment (Premorbid Adjustment Scale). Pooled DNA of 20Caucasian healthy males, without psychiatric history in their firstand second degree relatives, was used as reference in hybridizations.Array CGH analyses were performed using Agilent Human GenomeMicroarray 244 K (genome-wide coverage) and results were vali-dated with RT-PCR. Significant differences were observed betweenearly onset patients (≤18 years) and adult onset patients(≥19 years) in chromosome 17q21: p<0.01 (Benjamini-Hochberg(adjusted)). Gains in this chromosomal region were detected in 7early onset patients and in 1 adult onset patient while losses wereobserved in 8 adult onset patients. IQ did not significantly account forthe observed differences in the present sample. These results suggest

the implication of the genomic variability detected in 17q21 inunderlying a significant proportion of illness age at expression andwarrant further analyses of the genomic variability of this region. Inthis sense, it is interesting to note that this chromosomal regionencompasses the microtubule-associated protein Tau gene (MAPT),which has been associatedwith neurodegenerative disorders such asParkinson disease or Frontotemporal dementia. Additionally, chro-mosomal imbalances in this region have been detected in individualswith mental retardation and dysmorphic features. Moreover, thisgenomic interval has recently been documented to harbor a common<900 kb inversion polymorphism, resulting in a haplotype blockwith two highly divergent haplotypes designated as H1 andH2. H2 isapparently under positive selection and is found at a frequency of20% in the European population. Results of a SNP screening of thisregion in a larger sample of psychotic patients and their relativeswillbe also presented in the symposium. Acknowledgements: NarsadFoundation Research Award 2008, Fundación Alicia Koplowitz(2006), Fundació La Marató de TV3 (014430/31).

doi:10.1016/j.schres.2010.02.113

RARE PATHOGENIC COPY NUMBER MUTATIONS INMENTAL DISORDERS

David CollierInstitute of Psychiatry, Kings College, London, UK

Rare structural variants may account for a larger fraction of theoverall genetic risk than previously assumed. In contrast to raresingle nucleotide mutations, rare copy number variations (CNVs)can be detected using genome- wide single nucleotide polymor-phism arrays. This has led to the identification of CNVs associatedwith mental retardation and autism. In a genome- wide search forCNVs associating with schizophrenia, we used a population-basedsample to identify de novo CNVs by analysing 9,878 transmissionsfrom parents to offspring. The 66 de novo CNVs identified weretested for association in a sample of 1,433 schizophrenia cases and33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3showing nominal association with schizophrenia in the firstsample (phase I) were followed up in a second sample of 3,285cases and 7,951 controls (phase II). All three deletions significantlyassociate with schizophrenia and related psychoses in thecombined sample. The identification of these rare, recurrent riskvariants, having occurred independently in multiple founders andbeing subject to negative selection, is important in itself. CNVanalysis may also point the way to the identification of additionaland more prevalent risk variants in genes and pathways involvedin schizophrenia.

doi:10.1016/j.schres.2010.02.114

Symposium 20FUTURE DIRECTIONS FOR THE NEUROPATHOLOGYOF SCHIZOPHRENIACo-Chairpersons: David Cotter, Paul HarrisonTuesday, 13 April, 2010 - 3:30 pm - 5:30 pm

Overall Abstract: This symposium will summarise the value ofpost-mortem brain research in schizophrenia and to discuss thepossible future directions of work in this area. Common themes

Abstracts140