| Literature DB >> 27013732 |
Anastasia Vedenko1, Jesse V Kurland1, Luis A Barrera1,2,3,4, Julia M Rogers1,2, Stephen S Gisselbrecht1, Elizabeth J Rossin3,5,6, Jaie Woodard1,2, Luca Mariani1, Kian Hong Kock1,7, Sachi Inukai1, Trevor Siggers1, Leila Shokri1, Raluca Gordân1, Nidhi Sahni8,9, Chris Cotsapas5,6, Tong Hao8,9, Song Yi8,9, Manolis Kellis4,6, Mark J Daly5,6,10, Marc Vidal8,9, David E Hill8,9, Martha L Bulyk1,2,3,6,7,8,11.
Abstract
Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.Entities:
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Year: 2016 PMID： 27013732 PMCID： PMC4825693 DOI： 10.1126/science.aad2257
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728