Search: onr:"swepub:oai:DiVA.org:uu-297809" >
Allele-specific tra...
Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression
-
- Cavalli, Marco (author)
- Uppsala universitet,Medicinsk genetik och genomik
-
- Pan, Gang (author)
- Uppsala universitet,Medicinsk genetik och genomik
-
- Nord, Helena (author)
- Uppsala universitet,Medicinsk genetik och genomik
-
show more...
-
- Wallerman, Ola (author)
- Uppsala universitet,Medicinsk genetik och genomik
-
- Arzt, Emelie Wallén (author)
- Uppsala universitet,Medicinsk genetik och genomik,Karolinska Inst, Dept Biosci & Nutr, Ctr Biosci, Huddinge, Sweden.
-
- Berggren, Olof (author)
- Uppsala universitet,Reumatologi
-
- Elvers, Ingegerd (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Broad Inst MIT & Harvard, Cambridge, MA USA.
-
- Eloranta, Maija-Leena (author)
- Uppsala universitet,Reumatologi
-
- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi
-
- Toh, Kerstin Lindblad (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Broad Inst MIT & Harvard, Cambridge, MA USA.
-
- Wadelius, Claes (author)
- Uppsala universitet,Medicinsk genetik och genomik
-
show less...
-
(creator_code:org_t)
- 2016-03-18
- 2016
- English.
-
In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 135:5, s. 485-497
- Related links:
-
https://uu.diva-port... (primary) (Raw object)
-
show more...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Cavalli, Marco
-
Pan, Gang
-
Nord, Helena
-
Wallerman, Ola
-
Arzt, Emelie Wal ...
-
Berggren, Olof
-
show more...
-
Elvers, Ingegerd
-
Eloranta, Maija- ...
-
Rönnblom, Lars
-
Toh, Kerstin Lin ...
-
Wadelius, Claes
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Medical Genetics
- Articles in the publication
-
Human Genetics
- By the university
-
Uppsala University
-
Karolinska Institutet