Neuron-specific impairment of inter-chromosomal pairing and transcription in a novel model of human 15q-duplication syndrome
| Project/Area Number |
21710193
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
基礎ゲノム科学
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| Research Institution | Kanazawa University |
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Principal Investigator |
HORIKE Shinichi Kanazawa University, フロンティアサイエンス機構, 特任助教 (40448311)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 自閉症 / 染色体工学 / エピジェネティクス / 15q11-q13 / インプリンティング / ゲノム / 遺伝子 / 発現制御 / 染色体 / クロマチン |
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| Research Abstract |
The most common recurrent cytogenetic abnormalities in autism spectrum disorders involve maternally derived duplications of the imprinted domain on chromosome 15q11-q13. Therefore characterizing the epigenetic chromatin organization of 15q11-q13 is important for understanding normal neuronal development. In this study, we focused on the homologous 15q11-q13 pairing in human neuronal cells. Our aim is to understand how the homologous pairing of 15q11-q13 is organized in the mammalian brain and associated with gene expression within the paired regions. In order to model 15q11-q13 maternal duplication in a neuronal cell line, a maternal copy of human chromosome 15 was transferred into the human SH-SY5Y neuronal cells by microcell fusion. As expected, homologous 15q11-q13 pairing was disrupted in human neuronal cells with an extra maternal copy of human chromosome 15. Interestingly, gene expression analysis of 15q11-q13 transcripts demonstrated significantly decreased expression of SNRPN, GABRB3, CHRNA7 transcripts despite increased maternal dosage. These results suggested that gene expression can be altered in unexpected ways through epigenetic changes resulting from increased maternal 15q11-13 dosage.
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Report
(3 results)
Research Products
(28 results)
