2000 Fiscal Year Final Research Report Summary
IDENTIFICATION OF LOCI SUSCEPTIBLE TO THE DEVELOPMENT OF SCHIZOPHERNIA BASED ON WHOLE GENOME LINKAGE FINDINGS
| Project/Area Number |
11672250
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | UNIVERSITY OF TSUKUBA |
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Principal Investigator |
ARINAMI Tadao BASIC MEDICAL SCIENCES, UNIVERSITY OF TSUKUBA ASSOCIATE PROFESSOR, 基礎医学系, 助教授 (10212648)
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| Project Period (FY) |
1999 – 2000
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| Keywords | SCHIZOPHRENIA / LINKAGE ANALYSIS / RESPONSIVE SEARCH EYE MOVEMENT / AFFECTED SIB PAIR ANA LYSIS |
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| Research Abstract |
This study has been carried out to identify genetic loci affecting susceptibility to the development of schizophrenia. Since linkage analysis needs many familial sample with multiple affecteds, we performed collaborative works One of such collaborative study group was JSSLG (Japanese Schizophrenia Sib-pair Linkage Group) and the other was quantitative linkage analysis for exploratory eye movement associated with schizophrenia.
The JSSLG is a multisite collaborative study group designed to create a national resource for linkage studies of schizophrenia in Japanese. An initial genome-wide scan is being carried out by genotyping short-tandem repeat (STR) markers in 138 families with 160 affected sib-pairs who have been collected at 16 sites throughout Japan. Inclusion criteria for this collaborative study are schizophrenia for probands and schizophrenia or schizoaffective disorder for their affected co-sibs. Data by genotyping 249 markers on 15 chromosomes indicate possible linkage regions
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on chromosome 2p and 2q.
As an another study, we performed a genome-wide search for a locus responsible for exploratory eye movement (EEM), a quantitative trait measure associated with schizophrenia. A 10-cM resolution genome-wide linkage analysis between the EEM disturbance and 358 highly polymorphic microsatellite markers in 38 nuclear families with 122 members (38 probands, 47 siblings, and 37 parents) including 58 sib-pairs was performed. The GCT10C10 marker on chromosome 22q11.2 yielded the strongest linkage (LOD=3.48, p=3.1×10-5) in parametric quantitative trait loci (QTL) analysis. The smallest p value was also observed at the GCT10C10 marker (Z=2.27, p=0.012) with nonparametric analysis. Our findings suggest that schizophrenia-specific quantitative trait such as EEM may offer augmented power in linkage analysis of schizophrenia. We propose that the EEM trait may be a promising tool for identifying gene(s) relating to the etiology of schizophrenia. We speculate that the loci on chromosome 22q11.2 corresponding to the EEM phenotype identified by our linkage analysis may eventually aid in detecting gene(s) associated with schizophrenia. Less
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