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解决马赛克变体的染色质影响,使用向的Fiber-seq

Stephanie C Bohaczuk¹, Zachary J Amador², Chang Li¹

¹Division of Medical Genetics, University of Washington School of Medicine, Seattle, WA, USA.

bioRxiv : the preprint server for biology

|July 19, 2024

概括

向单分子色素纤维测序 (Fiber-seq) 能够精确地绘制DNA序列和色素可访问性的地图. 这种方法揭示了非编码变体如何影响基因调节和疾病,比如肌性衰竭1.

科学领域:

基因组学就是基因组学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
分子生物学分子生物学

背景情况:

传统的染色体测定DNA片段,防止单个分子同时进行序列和染色体结构分析.
准确量化非编码马赛克变体的功能影响需要将DNA序列与单个DNA分子的染色质可访问性配对.

研究的目的:

引入和验证针对性单分子色素纤维测序 (Fiber-seq) 以实现高分辨率,长时间读取的基因组和表观基因组分析.
为了研究1型肌性发育不良症中病原性重复扩张对染色质结构和调节元素的影响.
评估治疗性腺基编辑对全球因基因促进体的表观遗传效应.

主要方法:

针对性单分子色素纤维测序 (Fiber-seq) 用于同时进行长读基因组和表观基因组分析.
在肌性缩症中对体质不稳定性和调节元件干扰的分析 1.
对人类造血细胞中的全球蛋白基因促进体的腺基编辑效应的评估.

主要成果:

纤维-seq实现了目标>100千基基位点的~10倍丰富,使单分子分析成为可能.
致病性CTG重复扩张在肌性发育不良1呈现重复的长度依赖的体质不稳定性和调节元件的破坏.
治疗性腺基编辑增加了人类造血细胞中*HBG1*促进体和邻近的调节元件的可访问性.

结论:

定向光纤seq是一个强大的工具,用于剖析非编码马赛克变体的功能后果.
非编码变体可以对染色体结构和基因调节产生复杂的,远程的影响.
了解这些分子机制对于开发遗传疾病治疗方法至关重要.

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