精子細胞における染色体分離の誤差の原因となるメオティック再結合の年齢依存的変異
Maciej J Zelazowski1, Maria Sandoval1, Lakshmi Paniker1
1Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Cell
|September 26, 2017
まとめ
青年マウスは,代替修復経路により,微分期間のクロスオーバー (CO) リコンビネーションが減少した. この非効率的なCO成熟は染色体の誤差分離のリスクを高め,若い男性におけるダウン症候群の発生を説明する可能性がある.
科学分野:
- 遺伝学
- 細胞生物学
- 生殖生物学
背景:
- 微分化の過程で忠実に染色体分離することは 繁殖に不可欠です
- メオシスにはクロスオーバー (CO) リコンビネーションが必要で,同性染色体ペアごとに少なくとも1つのCOを保証する規制メカニズムが必要です.
研究 の 目的:
- 若いオスのマウスのCO不全の原因と結果を調査する.
- 若い男性におけるCOの減少の原因である分子メカニズムと,そのアヌプロイド性との関連性を調べる.
主な方法:
- 再結合を監視する全ゲノム細胞分析
- リコンビネーションホットスポットでの 分子測定
- MLH3を欠いたマウスの再結合の分析
- 人間の精子細胞におけるMutLγ焦点密度の評価
主要な成果:
- 幼いマウスの精子細胞は,成人精子細胞と比較して,かなり少ないCOsを示します.
- MLH3が欠けている未成年のマウスでは,構造選択核酸と代替複合体を含む代替経路の利用が増加し,COsを犠牲にして非クロスオーバー (NCOs) につながります.
- 若いヒトの精子細胞では,より低いMutLγ焦点密度が観察されました.
結論:
- 代替修復経路の不適切な活動は,若いオスのマウスのCO成熟を阻害し,潜在的に染色体の分離を妨げます.
- 若い男性におけるCO成熟効率の低下は,ダウン症児の出産リスクの上昇に寄与する.
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