Publication Date:
2013-09-17
Description:
Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project--the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918453/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918453/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lappalainen, Tuuli -- Sammeth, Michael -- Friedlander, Marc R -- 't Hoen, Peter A C -- Monlong, Jean -- Rivas, Manuel A -- Gonzalez-Porta, Mar -- Kurbatova, Natalja -- Griebel, Thasso -- Ferreira, Pedro G -- Barann, Matthias -- Wieland, Thomas -- Greger, Liliana -- van Iterson, Maarten -- Almlof, Jonas -- Ribeca, Paolo -- Pulyakhina, Irina -- Esser, Daniela -- Giger, Thomas -- Tikhonov, Andrew -- Sultan, Marc -- Bertier, Gabrielle -- MacArthur, Daniel G -- Lek, Monkol -- Lizano, Esther -- Buermans, Henk P J -- Padioleau, Ismael -- Schwarzmayr, Thomas -- Karlberg, Olof -- Ongen, Halit -- Kilpinen, Helena -- Beltran, Sergi -- Gut, Marta -- Kahlem, Katja -- Amstislavskiy, Vyacheslav -- Stegle, Oliver -- Pirinen, Matti -- Montgomery, Stephen B -- Donnelly, Peter -- McCarthy, Mark I -- Flicek, Paul -- Strom, Tim M -- Geuvadis Consortium -- Lehrach, Hans -- Schreiber, Stefan -- Sudbrak, Ralf -- Carracedo, Angel -- Antonarakis, Stylianos E -- Hasler, Robert -- Syvanen, Ann-Christine -- van Ommen, Gert-Jan -- Brazma, Alvis -- Meitinger, Thomas -- Rosenstiel, Philip -- Guigo, Roderic -- Gut, Ivo G -- Estivill, Xavier -- Dermitzakis, Emmanouil T -- 075491/Z/04/B/Wellcome Trust/United Kingdom -- 076113/Wellcome Trust/United Kingdom -- 081917/Wellcome Trust/United Kingdom -- 083270/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 085532/Wellcome Trust/United Kingdom -- 090367/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 095552/Z/11/Z/Wellcome Trust/United Kingdom -- 098381/Wellcome Trust/United Kingdom -- G0601261/Medical Research Council/United Kingdom -- MH090941/MH/NIMH NIH HHS/ -- R01 GM104371/GM/NIGMS NIH HHS/ -- R01 MH090941/MH/NIMH NIH HHS/ -- WT085532/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Sep 26;501(7468):506-11. doi: 10.1038/nature12531. Epub 2013 Sep 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland. tuuli.e.lappalainen@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24037378" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Cell Line, Transformed
;
Exons/genetics
;
Gene Expression Profiling
;
Genetic Variation/*genetics
;
Genome, Human/*genetics
;
*High-Throughput Nucleotide Sequencing
;
Humans
;
Polymorphism, Single Nucleotide/genetics
;
Quantitative Trait Loci/genetics
;
RNA, Messenger/analysis/genetics
;
*Sequence Analysis, RNA
;
Transcriptome/*genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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