Related Experiment Video
Updated: Jan 14, 2026
06:38
High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
Published on: February 7, 2019
9.2K
baal-nf identifies motif-disrupting variants that decrease transcription factor binding affinity
Breeshey Roskams-Hieter1,2, Øyvind Almelid3, Chris P Ponting4
1Institute of Genetics and Cancer, MRC Human Genetics Unit, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK. b.j.roskams-hieter@sms.ed.ac.uk.
Genome Biology
|January 12, 2026
Summary
Researchers identified 1,935 genetic variants that may alter human traits by changing transcription factor binding. This discovery aids in understanding the genetic basis of human variation.
Area of Science:
- Genetics
- Genomics
- Molecular Biology
Background:
- Human traits exhibit genetic variation, partly due to changes in transcription factor binding affinity within gene regulatory regions.
- Identifying specific trait-causal variants and their mechanisms remains a challenge in genetics.
Purpose of the Study:
- To identify and propose candidate variants causally altering human traits.
- To develop a method for investigating trait variation linked to altered transcription factor binding.
Main Methods:
- Utilized baal-nf, a computational tool, to analyze chromatin immunoprecipitation-sequencing data.
- Identified allele-specific binding sites at heterozygous loci within transcription factor and co-factor binding motifs.
- Focused on affinity-concordant positions to pinpoint functional variants.
Main Results:
- Proposed 1,935 variants as strong candidates for causally altering human traits.
- Demonstrated that these identified allele-specific binding sites are evolutionarily conserved.
- Showed enrichment of these sites for associations with human traits and gene expression.
Conclusions:
- The baal-nf method effectively identifies high-quality allele-specific binding sites.
- These findings provide a valuable resource for studying the genetic underpinnings of human trait variation.
- Altered transcription factor binding is a significant mechanism contributing to human trait diversity.
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