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DNase I sensitivity QTLs are a major determinant of human expression variation

DNase I sensitivity QTLs are a major determinant of human expression variation. Jacob F. Degner et all. Nature. Presenter: Tianyin Zhou 10/10/2012. Motivation. eQTL ---- expression quantitative trait loci A region of genome (might contain several SNPs)

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DNase I sensitivity QTLs are a major determinant of human expression variation

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  1. DNase I sensitivity QTLs are a major determinant of human expression variation Jacob F. Degner et all. Nature. Presenter: Tianyin Zhou 10/10/2012

  2. Motivation • eQTL ---- expression quantitative trait loci • A region of genome (might contain several SNPs) • Genetic variants(SNPs) within that region affect gene expression • Identified by genome-wide association study(GWAS) • Sequencing data for multiple individuals • Expression data for multiple individuals eQTL Expression What is the underlying mechanism?

  3. Conclusion Genetic variant gene expression difference mainly through Modifying chromatin accessibility and transcription factor binding Implications: SNPs not within a transcription factor binding site can also affect the gene expression, and thus under selection. Raise new unanswered question: How genetic variants modify chromatin accessibility?

  4. Technique and Data Use DNase I sequencing data to measure chromatin accessibility, focusing on DHS(DNase I hypersensitive sites only) Why 70 individuals? (GWAS study, statistical power) Available gene expression data • DNase I sequencing of 70 Yoruba lymphoblastoid cell lines

  5. Identification of dsQTL • dsQTL ---- DNase I sensitivity QTL • A region of genome genetic variants within which affect local chromatin accessibility (100bp overlapping window) • How local? • distance(genetic variant, chromatin accessibility window) < 40kb • 8902 eQTLs identified

  6. Properties of dsQTLs • For dsQTLs that lie within the target DHS On average affect chromatin accessibility for about 200-300bp

  7. Properties of dsQTLs (cont.) Most dsQTLs are generated by variants close to the target DHS window. Alleles within TFBS associated with a higher score of the position weight matrix also have higher chromatin accessibility Consistent with the expectation that Higher transcription factor binding affinity leads to more open chromatin

  8. Relationship between dsQTLs and eQTLs • dsQTL is very likely to be an eQTL for the nearby genes • 55% of the most significant eQTL SNPs are also dsQTLs • 39% of the dsQTLs are also eQTLs

  9. Relationship between dsQTLs and eQTLs For most (70%) of the joint dsQTL-eQTLs, allele associated with increased chromatin accessibility was also associated with increased gene expression level Genetic variant leads to gene expression difference mainly through Modifying chromatin accessibility and transcription factor binding Strongest evidence that Allele associated with increased accessibility - A

  10. Joint dsQTL-eQTLs • Most joint dsQTL-eQTLs lie close to the gene TSS.

  11. Thank you

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