Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
Show others and affiliations
2016 (English)In: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 135, no 5, 485-497 p.Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

Genome-wide association studies (GWAS) have identified a large number of disease-associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for transcription factors binding preferentially to one allele. We found 9962 candidate regulatory SNPs, of which 16 % were rare and showed evidence of larger functional effect than common ones. Functionally rare variants may explain divergent GWAS results between populations and are candidates for a partial explanation of the missing heritability. The majority of allele-specific variants (96 %) were specific to a cell type. Furthermore, by examining GWAS loci we found >400 allele-specific candidate SNPs, 141 of which were highly relevant in our cell types. Functionally validated SNPs support identification of an SNP in SYNGR1 which may expose to the risk of rheumatoid arthritis and primary biliary cirrhosis, as well as an SNP in the last intron of COG6 exposing to the risk of psoriasis. We propose that by repeating the ChIP-seq experiments of 20 selected transcription factors in three to ten people, the most common polymorphisms can be interrogated for allele-specific binding. Our strategy may help to remove the current bottleneck in functional annotation of the genome.

Place, publisher, year, edition, pages
2016. Vol. 135, no 5, 485-497 p.
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-297809DOI: 10.1007/s00439-016-1654-xISI: 000374459200004PubMedID: 26993500OAI: oai:DiVA.org:uu-297809DiVA: diva2:943497
Funder
Swedish National Infrastructure for Computing (SNIC), b2010003Swedish National Infrastructure for Computing (SNIC), b2011107Swedish Research Council, 541-2013-8161Swedish Diabetes AssociationKnut and Alice Wallenberg Foundation
Available from: 2016-06-28 Created: 2016-06-28 Last updated: 2017-11-28Bibliographically approved

Open Access in DiVA

fulltext(2711 kB)306 downloads
File information
File name FULLTEXT01.pdfFile size 2711 kBChecksum SHA-512
2bd4f184f4fc3c51e28c6e05e5511ace0ea1bfdc544776303ed39e37b1264e4e172ff3d5da9d5d4e2f53ba86e9b49b9e20637d9acee2020048dad83cee36f6ac
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Cavalli, MarcoPan, GangWallerman, OlaBerggren, OlofElvers, IngegerdEloranta, Maija-LeenaRönnblom, LarsToh, Kerstin LindbladWadelius, Claes
By organisation
Medicinsk genetik och genomikRheumatologyDepartment of Medical Biochemistry and Microbiology
In the same journal
Human Genetics
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 306 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 808 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf