2011 Fiscal Year Final Research Report
Molecular evolutionary analysis of schizophrenia susceptibility genes.
Project/Area Number |
21590360
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human genetics
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Research Institution | Kyushu University |
Principal Investigator |
SHIBATA Hiroki 九州大学, 生体防御医学研究所・ゲノム機能学分野 (80315093)
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Project Period (FY) |
2009 – 2011
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Keywords | 進化医学 / 集団遺伝学 / 自然選択 / 統合失調症 |
Research Abstract |
Schizophrenia has a relatively strong genetic background(λs=10). Because of the typically adolescent onset and the loss of sociality in patients, schizophrenia susceptibility alleles are expected to be selected out through generations. However, the prevalence is stably high at~ 1% in any of the populations surveyed. To explain the paradox, I hypothesized that the schizophrenia susceptibility alleles are maintained by the non-neutral process such as balancing selection. To test this hypothesis, I sequenced six schizophrenia susceptibility genes, BDNF, SLC18A1, COMT, DRD1, DRD2, DRD4 from 72 unrelated humans(24 Caucasians, 24 African Ameericans and 24 Japanese) and 24 unrelated chimpanzees as non-human controls. Using the variation data set, I examined neutrality by the summary statistics approach such as Tajima' s method. I identified a significant signal of balancing selection in the regions of coding SNPs in DRD2(rs6275, rs6277) and in COMT(rs4680). All of these SNPs a significant association has been frequently reported with schizophrenia. By coalescent simulation I dated the haplotypes in the selected regions in both genes to be> 1 MYA. I conclude that some of the schizophrenia susceptible alleles have been maintained by balancing selection of which the target may be the phenotypes related to schizophrenia as well as human brain functions.
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Research Products
(25 results)
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[Journal Article] Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family2011
Author(s)
Miura S, Shibata H, Kida H, Noda K, Toyama T, Iwasaki N, Iwaki A, Ayabe M, Aizawa H, Taniwaki T, Fukumaki Y.
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Journal Title
Neurogenetics
Volume: 12(1)
Pages: 25-31
Peer Reviewed
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[Journal Article] Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia2011
Author(s)
Deng X, Takaki H, Wang L, Kuroki T, Nakahara T, Hashimoto K, Ninomiya H, Arinami T, Inada T, Ujike H, Itokawa M, Tochigi M, Watanabe Y, Someya T, Kunugi H, Iwata N, Ozaki N, Shibata H, Fukumaki Y.
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Journal Title
Am J Med Genet Neuropsychiatr Genet
Volume: 156(7)
Pages: 850-858
Peer Reviewed
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[Journal Article] The identification and functional implications of human-specific" fixed" amino acid substitutions in the glutamate receptor family2009
Author(s)
Goto H, Watanabe K, Araragi N, Kageyama R, Tanaka K, Kuroki Y, Toyoda A, Hattori M, Sakaki Y, Fujiyama A, Fukumaki Y, Shibata H.
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Journal Title
BMC Evol Biol
Volume: 9
Pages: 224
Peer Reviewed
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[Presentation] Population specific susceptibility to Crohn' s disease and signals of natural selection on standing variation2011
Author(s)
Nakagome S, Mano S, Kozlowski L, Bujnicki JM, Shibata H, Fukumaki Y, Kidd JR, Kidd KK, Kawamura S, Oota H.
Organizer
12th International Congress of Human Genetics/61st Annual Meeting of The American Society of Human Genetics
Place of Presentation
Montreal, Canada
Year and Date
20111011-15
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