表观遗传学——生物学背景

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基础原理与生物学背景

基因组学

The Genome Reference Consortium
The complete sequence of a human genome
DNA GWAS

Genome phenotypes

• 常用的大约有27000左右个基因
• Protein coding gene median length = 26,288bp
• Protein coding gene mean length = 66,577bp
• Shortest KRTAP6-2 189bp chr21
• Longest RBFOX1 2,473,559 chr16
• mRNA mean 3392, median 2787bp
• mRNA shortest 186 bp (DEFB133, chr6)
• mRNA longest 109,224 bp (TTN, chr2)

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Mathias Girbig et al., Nat Rev Mol Cell Bio, 202

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https://en.wikipedia.org/wiki/File:Gene_structure_eukaryote_2_annotated.svg

基因的转录与调控

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Vivian Tam et al., 2019, Nat Rev Genetics

主要成就，孟德尔遗传疾病数据库：
• OMIM数据库
• ClinVar数据库

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Quantifying missing heritability at known GWAS loci

表观遗传学：

• DNA序列相同;
• 表型不同;
• 特征可遗传

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Patrick Cramer, Nature, 2019

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Mathias Girbig et al., Nat Rev Mol Cell Bio, 2022

确定转录的起始位点

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Mathias Girbig et al., Nat Rev Mol Cell Bio, 2022

确定正在转录的位点

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Mathias Girbig et al., Nat Rev Mol Cell Bio, 2022

通过转录起始测序，确定转录是双向的

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William K. M. Lai and B. Franklin Pugh, Nat Rev Genetics, 2017

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Sandy L. Klemm et al., Nat Rev Genetics, 2019

如何定量染色质的可及性？

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Sandy L. Klemm et al., Nat Rev Genetics, 2019

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Hiroshi Kimura, Journal of Human Genetics, 2013

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Vicky W. Zhou et al., Nat Rev Genetics, 2011

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Artem Barski et al., Cell, 2007

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Kateryna D. Makova and Ross C. Hardison, Nat Rev Genetics, 2015

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Peter Hugo Lodewijk Krijger and Wouter de Laat, Nat Rev Mol Cel Bio, 2016

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Peter Hugo Lodewijk Krijger and Wouter de Laat, Nat Rev Mol Cel Bio, 2016

数据的回贴与比对

转录因子ChIP-seq数据分析

组蛋白修饰的ChIP-seq

染色质的开放性

应用Tn5改进的少量样品技术