Linkage of Familial Schizophrenia to Chromosome 13q32

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
The American Journal of Human Genetics (Impact Factor: 10.93). 11/1999; 65(4):1096-103. DOI: 10.1086/302579
Source: PubMed


Over the past 4 years, a number of investigators have reported findings suggestive of linkage to schizophrenia, with markers on chromosomes 13q32 and 8p21, with one recent study by Blouin et al. reporting significant linkage to these regions. As part of an ongoing genome scan, we evaluated microsatellite markers spanning chromosomes 8 and 13, for linkage to schizophrenia, in 21 extended Canadian families. Families were analyzed under autosomal dominant and recessive models, with broad and narrow definitions of schizophrenia. All models produced positive LOD scores with markers on 13q, with higher scores under the recessive models. The maximum three-point LOD scores were obtained under the recessive-broad model: 3.92 at recombination fraction (theta).1 with D13S793, under homogeneity, and 4.42 with alpha=.65 and straight theta=0 with D13S793, under heterogeneity. Positive LOD scores were also obtained, under all models, for markers on 8p. Although a maximum two-point LOD score of 3.49 was obtained under the dominant-narrow model with D8S136 at straight theta=0.1, multipoint analysis with closely flanking markers reduced the maximum LOD score in this region to 2. 13. These results provide independent significant evidence of linkage of a schizophrenia-susceptibility locus to markers on 13q32 and support the presence of a second susceptibility locus on 8p21.

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Available from: Kathy Anne Hodgkinson, Mar 31, 2015
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    • "This replicated the earlier finding of a LOD score of 1.61 for marker D13S144 by Lin et al. [12]. Brzustowicz et al. [27] analyzed 21 Canadian families with schizophrenia and found genome-wide significant LOD scores on 13q. Brzustowicz et al. [28], using the same dataset and multipoint analysis and found a maximum LOD score of 3.81 with an empirical p = 0.02 under a recessive-broad model of schizophrenia at D13S793, with an estimated 65% of families linked to this region. "
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    ABSTRACT: We report analyses of a Brazilian study of early onset schizophrenia (BEOS) families. We genotyped 22 members of 4 families on a linkage SNP array and report here non-parametric linkage analyses using MERLIN® software. We found suggestive evidence for linkage on two chromosomal regions, 13q32 and 11p15.4. A LOD score of 2.71 was observed at 13q32 with a one LOD interval extending from 60.63-92.35 cM. From simulations, this LOD score gave a genome-wide empirical corrected p = 0.33, after accounting for all markers tested. Similarly 11p15.4 showed the same maximum LOD of 2.71 and a narrower one LOD interval of 4-14 cM. Of these, 13q32 has been reported to be linked to schizophrenia by multiple different studies. Thus, our study provides additional supporting evidence for an aetiological role of variants at 13q32 in schizophrenia.
    Full-text · Article · Dec 2012 · PLoS ONE
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    • "A large number of linkage analysis studies have shown putative candidate genes whose protein products are associated with lipid metabolism in schizophrenic patients and their family members (Moises et al., 1995; Pulver et al., 1995; Straub et al., 1997; Blouin et al., 1998; Hovatta et al., 1998; Shaw et al., 1998; Barnes et al., 1999; Brzustowicz et al., 1999; Gurling et al., 1999; Mors and Ewald, 1999; Riley and Williamson, 2000; Table 2). Among these, micro-deletion of chromosome 22q11 results in the development of a form of schizophrenia among 30% of children with this deletion (Karayiorgou et al., 2010). "
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    ABSTRACT: THE MULTIPLE ETIOLOGIES OF SCHIZOPHRENIA PROMPT US TO RAISE THE QUESTION: what final common pathway can induce a convincing sense of the reality of the hallucinations in this disease? The observation that artificial stimulation of an intermediate order of neurons of a normal nervous system induces hallucinations indicates that the lateral entry of activity (not resulting from canonical synaptic transmission) at intermediate neuronal orders may provide a mechanism for hallucinations. Meaningful hallucinations can be de-constructed into an organized temporal sequence of internal sensations of associatively learned items that occur in the absence of any external stimuli. We hypothesize that these hallucinations are autonomously generated by the re-activation of pathological non-specific functional LINKs formed between the postsynaptic membranes at certain neuronal orders and are examined as a final common mechanism capable of explaining most of the features of the disease. Reversible and stabilizable hemi-fusion between simultaneously activated adjacent postsynaptic membranes is viewed as one of the normal mechanisms for functional LINK formation and is dependent on lipid membrane composition. Methods of removing the proteins that may traverse the non-specifically hemi-fused membrane segments and attempts to replace the phospholipid side chains to convert the membrane composition to a near-normal state may offer therapeutic opportunities.
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    • "Furthermore, a SNP in this region has been associated with severity scores on a severity scale of panic and agoraphobia symptoms [Erhardt et al., 2007]. Similarly, the region on chromosome 13 where we found evidence of heterogeneity has been implicated in multiple studies of both schizophrenia and bipolar disorder [Lin et al., 1997; Blouin et al., 1998; Shaw et al., 1998; Brzustowicz et al., 1999; Detera-Wadleigh et al., 1999; Kelsoe et al., 2001; Liu et al., 2001; Chumakov et al., 2002; Faraone et al., 2002; Hattori et al., 2003; Mulle et al., 2005; Cheng et al., 2006]. The most studied candidate locus in this region is G72(DAOA)/G30 [Hattori et al., 2003; Chen et al., 2004; Korostishevsky et al., 2004; Schumacher et al., 2004; Fallin et al., 2005; Detera- Wadleigh and McMahon, 2006; Williams et al., 2006; Li and He, 2007; Kvajo et al., 2008; Prata et al., 2008]. "
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    ABSTRACT: There is comorbidity and a possible genetic connection between Bipolar disease (BP) and panic disorder (PD). Genes may exist that increase risk to both PD and BP. We explored this possibility using data from a linkage study of PD (120 multiplex families; 37 had > or =1 BP member). We calculated 2-point lodscores maximized over male and female recombination fractions by classifying individuals with PD and/or BP as affected (PD + BP). Additionally, to shed light on possible heterogeneity, we examine the pedigrees containing a bipolar member (BP+) separately from those that do not (BP-), using a Predivided-Sample Test (PST). Linkage evidence for common genes for PD + BP was obtained on chromosomes 2 (lodscore = 4.6) and chromosome 12 (lodscore = 3.6). These locations had already been implicated using a PD-only diagnosis, although at both locations this was larger when a joint PD + BP diagnosis was used. Examining the BP+ families and BP- families separately indicates that both BP+ and BP- pedigrees are contributing to the peaks on chromosomes 2 and 12. However, the PST indicates different evidence of linkage is obtained from BP+ and BP- pedigrees on chromosome 13. Our findings are consistent with risk loci for the combined PD + BP phenotype on chromosomes 2 and 12. We also obtained evidence of heterogeneity on chromosome 13. The regions on chromosomes 12 and 13 identified here have previously been implicated as regions of interest for multiple psychiatric disorders, including BP.
    Full-text · Article · Dec 2009 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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