ヒトの染色体状態の遺伝的制御は,局所および遠隔染色体相互作用を含む
Fabian Grubert1, Judith B Zaugg2, Maya Kasowski1
1Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|August 25, 2015
まとめ
遺伝子変異は長期間の相互作用によって 遺伝子調節に影響を与え 病気に影響を与えます この研究では,多数の局所および遠隔ヒストン定量特征局部 (hQTL) を特定し,遺伝的変異がクロマチンおよび疾患のフェノタイプにどのように影響するか明らかにしました.
科学分野:
- ゲノミクス
- エピジェネティクス
- 人間 の 病気 の 遺伝
背景:
- 遺伝子変異が遺伝子調節に及ぼす影響を理解することは,ヒトの病気の研究にとって極めて重要です.
- 遠隔の分子フェノタイプに対する非コーディング変数の影響は,特に長距離相互作用に関して,ほとんど未調査のままである.
研究 の 目的:
- 非コーディング遺伝子変異が遠隔の分子フェノタイプに影響を与える程度を調査する.
- 局所および遠隔ヒストン定量特征局 (hQTLs) を特定し,遺伝子調節と疾患におけるその役割を理解する.
主な方法:
- 75のリンパ芽細胞細胞系 (LCL) でクロマチンプロファイリング (3つのヒストンマーク) の統合.
- LCL特有のHi-CとChIA-PETクロマチン接触マップを使用した.
- 局所および遠隔ヒストン定量特征局 (hQTLs) の分析
主要な成果:
- 局所および遠隔ヒストン定量特征局部 (hQTLs) の最大のコレクションの1つを発見しました.
- ディスタルQTLは,トポロジカルに関連したドメイン内で濃縮され,調整されたクロマチンの状態の変化を示した.
- ヒストンのQTLは,自己免疫疾患に関連した一般的な変異に対して濃縮されます.
結論:
- 遺伝的変異は,相互作用する規制要素における調整されたクロマチンの変化を通して,ヒトの疾患のフェノタイプに影響を与えることができます.
- 全ゲノム関連研究を用いて,疾患関連変異の推定標的遺伝子を特定した.
- 遺伝子変異が遺伝子調節と病気に影響を与えるメカニズムについての洞察を提供します.
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