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Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci
- Source :
- Genome research (Online) 23 (2013): 1130–1141. doi:10.1101/gr.155127.113, info:cnr-pdr/source/autori:Paul DS, Albers CA, Rendon A, Voss K, Stephens J; HaemGen Consortium, van der Harst P, Chambers JC, Soranzo N, Ouwehand WH, Deloukas P/titolo:Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci/doi:10.1101%2Fgr.155127.113/rivista:Genome research (Online)/anno:2013/pagina_da:1130/pagina_a:1141/intervallo_pagine:1130–1141/volume:23, Genome Res. 23, 1130-1141 (2013), Genome Research, 23(7), 1130-1141. Cold Spring Harbor Laboratory Press, Paul, D S, Albers, C A, Rendon, A, Voss, K, Stephens, J, Akkerman, J W, Algra, A, Al-Hussani, A, Allayee, H, Anni, F, Asselbergs, F W, Attwood, A, Balkau, B, Bandinelli, S, Bastardot, F, Basu, S, Baumeister, S E, Beckmann, J, Benyamin, B, Biino, G, Bis, J C, Bomba, L, Bonnefond, A, Boomsma, D I, Bradley, J R, Cambien, F, Ciullo, M, Cookson, W O, Cucca, F, Cvejic, A, d'Adamo, A P, Danesh, J, Danjou, F, Das, D, Davies, G, de Bakker, P I, de Boer, R A, de Geus, E J C, Deary, I J, Dedoussis, G V, Dimitriou, M, Dina, C, Döring, A, Elling, U, Ellinghaus, D, Elliott, P, Engström, G, Erdmann, J, Esko, T, Evans, D M, Eyjolfsson, G I, Falchi, M, Feng, W W, Ferreira, M A, Ferrucci, L, Fischer, K, Folsom, A R, Fortina, P, Franke, A, Franke, L, Frazer, I H, Froguel, P, Galanello, R, Ganesh, S, Garner, S F, Gasparini, P, Genser, B, Gibson, Q D, Gieger, C, Girotto, G, Glazer, N L, Gögele, M, Goodall, A H, Greinacher, A, Gudbjartsson, D F, Hammond, C J, Harris, S E, Hartiala, J, Hartikainen, A L, Hazen, S L, Heckbert, S R, Hedblad, B, Hengstenberg, C, Hersch, M, Hicks, A A, Holm, H, Hottenga, J J, Illig, T, Järvelin, M R, Jolley, J, Jupe, S, Kähönen, M, Kamatani, N, Kanoni, S, Kema, I P, Kemp, J P, Khadake, J, Khaw, K T, Kleber, M E, Kooner, J S, Kovacs, P, Kühnel, B, Kyrtsonis, M C, Labrune, Y, Lagou, V, Langenberg, C, Lehtimäki, T, Li, X, Liang, L, Lloyd-Jones, H, Loos, R J, Lopez, L M, Lumley, T, Lyytikäinen, L P, Maerz, W, Mägi, R, Mangino, M, Martin, N G, Maschio, A, Mateo Leach, I, McKnight, B, Meacham, S, Medland, S E, Meisinger, C, Melander, O, Memari, Y, Metspalu, A, Miller, K, Mitchell, B D, Moffatt, M F, Montgomery, G W, Moore, C, Murgia, F, Nakamura, Y, Nauck, M, Navis, G, Nolte, I M, Nöthlings, U, Nutile, T, Okada, Y, Olafsson, I, Onundarson, P T, O'Reilly, P F, Parracciani, D, Parsa, A, Penninger, J M, Penninx, B W J H, Pirastu, M, Pirastu, N, Pistis, G, Porcu, E, Portas, L, Porteous, D J, Pouta, A, Pramstaller, P P, Prokopenko, I, Psaty, B M, Pullat, J, Radhakrishnan, A, Raitakari, O, Ramirez-Solis, R, Ried, J S, Ring, S M, Robino, A, Rotter, J I, Ruggiero, D, Ruokonen, A, Sala, C, Saluments, A, Samani, N J, Sambrook, J, Sanna, S, Schlessinger, D, Schmidt, C O, Schreiber, S, Schunkert, H, Scott, J, Sehmi, J, Serbanovic-Canic, J, Shin, S Y, Shuldiner, A R, Sladek, R, Smit, J H, Smith, G D, Smith, J G, Smith, N L, Snieder, H, Sorice, R, Spector, T D, Starr, J M, Stefansson, K, Stemple, D, Stumvoll, M, Sulem, P, Takahashi, A, Tan, S T, Tanaka, T, Tang, C, Tang, W, Tang, W H, Taylor, K, Tenesa, A, Teumer, A, Thein, S, Thorsteinsdottir, U, Toniolo, D, Tönjes, A, Traglia, M, Uda, M, Ulivi, S, van der Schoot, E, van Gilst, W H, van Pelt, L J, van Veldhuisen, D J, Verweij, N, Visscher, P M, Völker, U, Vollenweider, P, Wareham, N J, Wernisch, L, Westra, H J, Whitfield, J B, Wichmann, H E, Wiggins, K L, Willemsen, G, Winkelmann, B R, Wirnsberger, G, Wolffenbuttel, B H, Yang, J, Yang, T P, Zhang, J H, Zhao, J H, Zitting, P, Zwaginga, JJ, van der Harst, P, Chambers, J C, Soranzo, N, Ouwehand, W H & Deloukas, P 2013, ' Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci ', Genome Research, vol. 23, no. 7, pp. 1130-1141 . https://doi.org/10.1101/gr.155127.113, Genome Research; Vol 23, Genome Research, 23(7), 1130-1141. COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
- Publication Year :
- 2013
- Publisher :
- COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2013.
-
Abstract
- To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits. Marie-Curie Initial Training Network NETSIM British Heart Foundation RG/09/12/28096 National Institutes for Health RP-PG-0310-1002 Wellcome Trust 098051 info:eu-repo/grantAgreement/EC/FP7/282510
- Subjects :
- Netherlands Twin Register (NTR)
Erythrocytes
Genome-wide association study
UNCERTAINTY
Regulatory Sequences, Nucleic Acid
VARIANTS
ANNOTATION
COLORECTAL-CANCER
Histones
0302 clinical medicine
BINDING
Cluster Analysis
Myeloid Cells
Genetics (clinical)
Genetics
hematological trait
0303 health sciences
Chromosome Mapping
MRP4 ABCC4
Chromatin
Nucleosomes
Phenotype
Organ Specificity
030220 oncology & carcinogenesis
Blood Platelets
Quantitative Trait Loci
Biology
Quantitative trait locus
Polymorphism, Single Nucleotide
DYNAMIN 3
03 medical and health sciences
Quantitative Trait, Heritable
MEGAKARYOCYTES
Humans
Cell Lineage
ddc:610
GENOME-WIDE ASSOCIATION
Enhancer
Transcription factor
Gene
ChIA-PET
030304 developmental biology
Research
Genetic Variation
DNA
Chromatin Assembly and Disassembly
Genetic architecture
Gene Expression Regulation
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 15495469, 10889051, and 03101002
- Volume :
- 23
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Genome Research
- Accession number :
- edsair.doi.dedup.....849ffee40270a44763bc105c5c53850e
- Full Text :
- https://doi.org/10.1101/gr.155127.113