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Endogenous fine-mapping of functional regulatory elements in complex genetic loci in HAP1 [CUT&Tag]

ABSTRACT: Endogenous fine-mapping of functional regulatory elements in complex genetic loci in HAP1 [CUT&Tag]

PROVIDER: PRJNA1205702 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31872265_1.fastq.gz	Fastqsanger.gz
	SRR31872265_2.fastq.gz	Fastqsanger.gz
	SRR31872266_1.fastq.gz	Fastqsanger.gz
	SRR31872266_2.fastq.gz	Fastqsanger.gz
	SRR31872267_1.fastq.gz	Fastqsanger.gz

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Endogenous fine-mapping of functional regulatory elements in complex genetic loci in HAP1 [CUT&Tag]

Project description:The majority of genetic loci linked to polygenic complex traits are found in non-coding regions of the human genome. These loci often exhibit complex gene regulatory relationships and linkage disequilibrium (LD) configurations, making it challenging to accurately identify causal variants and their target genes. We used multiplexed single-cell CRISPR interference and activation perturbations to investigate cis-regulatory element (CRE) and target gene expression relationships within tight LD in the endogenous chromatin context. We demonstrated the prevalence of multiple causality in perfect LD (pLD) for independent expression quantitative trait locus (eQTL) and uncovered fine-grained genetic effects on gene expression within pLD, which are difficult to decipher using traditional eQTL fine-mapping or existing computational methods. We found that over one third of the causal CREs lack classical epigenetic markers, and we functionally validated one of these hidden regulatory mechanisms. Leveraging Multiome single-cell epigenetic and sequence perturbations, we highlighted the regulatory plasticity of the human genome. Our study will guide the exploration of missing causal mechanisms in molecular trait formation and disease development.

2025-01-03 | GSE285718 | GEO

Endogenous fine-mapping of functional regulatory elements in complex genetic loci in HAP1

Project description:Endogenous fine-mapping of functional regulatory elements in complex genetic loci in HAP1

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