贝克威特-维德曼综合征和大后代综合征涉及甲基组,转录组和染色质配置的改变
medRxiv : the preprint server for health sciences
|January 3, 2024
概括
贝克威斯-维德曼综合征 (BWS) 是一种表观遗传过度生长障碍,涉及超出染色体11p15.5的全球表观遗传变化. 这项研究确定了两个BWS子组,并与一个牛模型共享表观遗传变化,帮助生物标志物发展.
科学领域:
- 表观遗传学和基因组学
- 发展生物学 发展生物学
- 比较医学是一种比较医学.
背景情况:
- 贝克威思-维德曼综合征 (BWS) 是最常见的表观遗传过度生长障碍,与染色体11p15的改变有关.
- 在约50%的BWS患者中,KvDMR1 (IC2) 区域的低甲基化发生.
- BWS与器官过度生长和儿童癌症风险增加有关.
研究的目的:
- 为了研究贝克威思-维德曼综合征 (BWS) 在11p15区域之外的全球表观遗传变化.
- 在BWS患者和动物模型中,在甲基组,转录组和染色质结构水平上描述完整的表观遗传特征.
- 确定潜在的生物标志物,以改善BWS的分子诊断.
主要方法:
- 贝克威思-维德曼综合征 (BWS) 患者的全面表观遗传概况,KvDMR1 (IC2) 低甲基化.
- 分析牛大后代综合征 (LOS) 作为BWS的动物模型.
- 全基因组对DNA甲基化,转录丰富度,RNA替代拼接,染色体区和拓关联域 (TAD) 的评估.
主要成果:
- 在BWS KvDMR1 (IC2) 中鉴定了两个新型分子子组. 低甲基化个体.
- 在BWS和LOS中检测DNA甲基化,基因表达和染色质结构中的全基因组表观遗传变化.
- 在人类BWS和牛LOS模型之间观察到共享的表观遗传变化,其中改变的染色质结构与差异性基因表达相关.
结论:
- 全球表观遗传变化在贝克维思-维德曼综合征 (BWS) 中超出了11p15染色体.
- 该研究在BWS中确定了不同的分子子组,并在物种之间保留了表观遗传变化.
- 这些发现突出了潜在的新基因和基因组区域,用于开发BWS的改进分子诊断生物标志物.
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