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Schizophrenia
1. Discovering Disease Genes- The Example of Schizophrenia Pippa Thomson, Medical Genetics Section, Dept of Medical Sciences, MMC, University of Edinburgh.
6. High Heels Cause Schizophrenia and 6 Other Outlandish Medical Theories 2. High-heeled shoes cause schizophrenia. You have to wonder where some medical theories originate. Why did Swedish scientist Jarl Flensmark decide to study a connection between heeled shoes and the incidence of schizophrenia ? The world may never know. But his initial research seems sound, and he has connected certain brain activity with stimulation of certain points on the feet. The spread of schizophrenia around the globe has closely followed the spread of availability of heeled shoes. Is it an eerie coincidence or a real cause for concern? Look out, men - this theory applies not only to stilettos, but to any shoe with a heel. remedicated.com
9. Allelic architecture and mapping strategy Magnitude of effect Frequency in population Family-based linkage studies Association studies in populations Unlikely to exist Fnct. Studies
14. ? recurrent major depression minor diagnosis unaffected schizophrenia bipolar affective disorder (1;11)(q42;q14) translocation translocation increases risk by 50-fold t(1;11) co-segregates with major mental illness
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17. SNPs are genotyped in parent-offspring trios, initially in CEPH trios. This can be used to identify SNPs that co-segregate (i.e. are in linkage disequilibrium) versus those that segregate independently. A subset of SNPs can therefore be chosen that best represent the genetic diversity in a region/gene, reducing the costs of genotyping. Summary of genotyped SNPs: Populations CEU CHB+JPT YRI Total Non-Redundant 3,204,709 3,244,897 3,150,433 International HapMap project http://www.hapmap.org/
18. Region of interest HapMap genotyped SNPs Known SNPs* Known genes in the regions Linkage Disequilibrium (LD) *http://www.ncbi.nlm.nih.gov/SNP/
19. Tagging SNP selection Proportion of haplotype diversity explained : SNPs 1-23 - 97% SNPs 24-46 - 98%
20. DISC2 TRANSLOCATION LOD=7.1, SCOTLAND Genetic evidence implicating DISC1 in psychiatric illness 1 SCZ & BPAD & MDD SCOTLAND SCZ , BPAD HAPLOTYPE p =0.0044, p =0.0016 2 3 4 5 6 7 8 9 10 11 12 13 DISC1 LOD=2, BRITAIN & ICELAND (Curtis et al 2003) D1S251 LOD=1, TAIWAN (Hwu et al 2003) SCZ BPAD HAPLOTYPE p =0.00024, FINLAND (Hennah et al 2003) SCZ & SCZAFF LOD=3.21, FINLAND (Ekelund et al 2001) SCZ D1S2709 p =0.000027, North-America (Hodgkinson et al 2004) rs6675281 SCZAFF
21. Table 1. Summary of current evidence supporting several of the more promising genes implicated in schizophrenia, bipolar disorder, and mixed bipolar-psychosis phenotypes Craddock et al., SCZ Bulletin, 2006 Genes for Schizophrenia ? >130 genes implicated
28. DISC1 Kirsty Millar Shaun Mackie Fumiaki Ogawa Jennifer Chubb Becky Carlyle Nick Bradshaw Sheila Christie Steve Clapcote Kathy Evans Sarah Brown William Hennah Medical Genetics Prof David Porteous Prof Douglas Blackwood Walter Muir Ben Pickard Other collaborators DISC1 Consortium Wellcome Trust CRF Illumina, San Diego Cold Spring Harbor laboratories Acknowledgements