| Project/Area Number |
09672310
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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 University of Tsukuba, Institute of Basic Medical Sciences, Associate Professor, 基礎医学系, 助教授 (10212648)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Schizophrenia / Chromosome22 / DiGeorge Syndrome / Dopamine D4 receptor gene / Gene expression / Polymorphism |
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| Research Abstract |
Since the recognition that adult patients with velocardiofacial syndrome (VCFS) show frequent psychotic symptoms, the 22q11.2 deletion has been proposed as one of the most common genetic syn- drome associated with schizophrenia. In studies of schizophrenic populations, deletions have been de- tected in more than 1% of schizophrenics, indicating the existence of many patients in whom this dele- tion has not been dianosed. In this study, we devised a PCR-based screening method for detecting 22q11.2 deletions, which involves a homozygous gene quantitative amplification of the KRAB-A region of the ZNF74 gene in the common 3-Mb deletion region of VCFS and its counterpart in X chromosome. By applying it to screen for deletions in genomic DNA from 300 schizophrenics and 300 controls, a woman with schizophrenia was detected to have the 22q11.2 deletion, which was thereafter confirmed by FISH.The patient was mildly retarded but did not have characteristic craniofacial, palatal or cardiac malfor
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mations. The present study supports the hypothesis that 22q 11.2 deletions increase the suscepti- bility for schizophrenia. The screening method described here help diagnose unremarkable patients with 22q11 deletions and delineate their clinical features irrespective of ascertainment strategies.
The human dopamine D4 receptor gene (DRD4) is an important candidate gene for schizophrenia. We identified a novel -521 C>T polymorphism in the 5'-promoter region of DRD4. A transient expres- sion method revealed that the T allele of this polymorphism reduces the transcriptional efficiency by 40% compared with the C allele. This polymorphism is of interest because of reported elevation of D4- like sites and DRD4 mRNA in the post-mortem schizophrenic brain. The C allele frequency was signifi- cantly higher in 252 Japanese schizophrenics (0.48) than in 269 Japanese controls (0.41) (p = 0.02) [odds ratio = 1.35 (95% confidence interval 1.05 - 1.72)]. Although the association is weak and should be considered tentative until other studies replicate it, this polymorphism provides a tool with the potential to examine whether DRD4 is related to susceptibility to and neuroleptic response in schizophrenia. Less
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