High-throughput identification of human SNPs affecting regulatory element activity

Area of Science:

• Genomics
• Molecular Biology
• Genetics

Background:

• Millions of single nucleotide polymorphisms (SNPs) reside in non-coding regions of the human genome, often overlapping with regulatory elements.
• Genome-wide association studies (GWAS) link SNPs to traits and gene expression but lack resolution to identify causal variants.
• Previous functional screens were too low-throughput to assess the vast number of SNPs for regulatory effects.

Purpose of the Study:

• To survey the effect of millions of SNPs on enhancer and promoter activity using a high-throughput reporter assay.
• To identify specific SNPs that modulate the activity of regulatory elements.
• To create a dataset that can be integrated with GWAS findings to pinpoint causal SNPs for human traits.

Main Methods:

• Utilized the survey of regulatory elements (SuRE) reporter technology for high-throughput SNP analysis.
• Assessed the impact of 5.9 million SNPs, encompassing 57% of common SNPs, on regulatory element activity.
• Analyzed enhancer and promoter activity in a cell-type-specific manner.

Main Results:

• Identified over 30,000 SNPs that significantly alter the activity of putative regulatory elements.
• Observed cell-type-specific effects for a portion of the identified SNPs.
• Generated a comprehensive dataset of SNP-regulatory element interactions.

Conclusions:

• The study provides a high-resolution map of SNP effects on gene regulation.
• The findings facilitate the identification of causal SNPs underlying GWAS associations.
• This resource aids in understanding the genetic basis of human traits and diseases.