多発性硬化症に不一致する一卵性双子のゲノム,エピゲノム,RNA配列は,多発性硬化症に不一致する
Sergio E Baranzini1, Joann Mudge, Jennifer C van Velkinburgh
1Department of Neurology, University of California at San Francisco, San Francisco, California 94143, USA. sebaran@cgl.ucsf.edu
Nature
|April 30, 2010
まとめ
多発性硬化症 (MS) の同卵性双生児は,有意な遺伝的または表遺伝的差異を示せず,環境要因だけで疾患の不一致を引き起こすという考えに異議を唱えました. この研究では,双子のゲノムとエピゲノムの配列を解析し,MS患者の自然対育成を理解しました.
科学分野:
- 遺伝学 遺伝学とは
- 免疫学 免疫学とは
- 神経科学は神経科学である.
背景:
- 一卵性双生児は,多発性硬化症 (MS) などの疾患に対する遺伝的対環境的影響を研究するために重要である.
- 一卵性双子のMS疾患の不一致は,伝統的に環境要因が重要な役割を果たしていることを示唆しています.
- 最近の発見は,同卵性双子の間の潜在的な遺伝的および表遺伝的多様性を示し,このモデルに疑問を投げかけています.
研究 の 目的:
- 多発性硬化症における不協和の単離子双子のペアの遺伝的,表遺伝的,およびトランスクリプトームの違いを調査する.
- このような違いが,同卵双子の間で観察されたMS発達の不一致を説明できるかどうかを判断する.
主な方法:
- 1つのMS-ディスコラントの同一双子のペアの全ゲノムシーケンシング.
- 3つのMS-不一致の同一双子のペアのCD4 (((+)) リンパ球のRNAトランスクリプトームとエピジェノームの配列決定.
- シングルヌクレオチドポリモルフィズム (SNP),挿入-消去ポリモルフィズム,HLAハプロタイプ,コピー数変数,DNAメチル化パターンの分析.
主要な成果:
- 複製可能な遺伝的差異 (SNP,indels) は同卵双子の間で見つかりませんでした.
- HLAハプロタイプ,MS感受性SNP,コピー数変異,または遺伝子発現における有意な差異は観察されなかった.
- 同胞同士の間には最小限の表遺伝的差異 (DNAメチル化) が検出され,関係のない個体や異なる組織との間よりもはるかに少ない.
結論:
- この研究では,一卵性双子のMS疾患の不一致を説明する遺伝的,表遺伝的,またはトランスクリプトームの違いの証拠は見つかりませんでした.
- これらの発見は,MSの病原性における一卵性双子の研究の伝統的な解釈に異議を唱える.
- この研究は,初めて報告された女性,双子,および自己免疫疾患の個々のゲノム配列を提供する.
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