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SUMMARY:Paper: Polymorphic Cis- and Trans-Regulation of Human Gene Express
 ion - Klara Stefflova (Cancer Research UK\, Cambridge Research Institute)
DTSTART:20101025T140000Z
DTEND:20101025T153000Z
UID:TALK25395@talks.cam.ac.uk
CONTACT:Stefan Gräf
DESCRIPTION:Cheung VG\, Nayak RR\, Wang IX\, Elwyn S\, Cousins SM\, et al.
   (2010)\nPolymorphic Cis- and Trans-Regulation of Human Gene Expression. 
 PLoS Biol\n8(9): e1000480. doi:10.1371/journal.pbio.1000480\n\nAbstract \
 n\nExpression levels of human genes vary extensively among individuals. Th
 is\nvariation facilitates analyses of expression levels as quantitative\np
 henotypes in genetic studies where the entire genome can be scanned for\nr
 egulators without prior knowledge of the regulatory mechanisms\, thus\nena
 bling the identification of unknown regulatory relationships. Here\, we\nc
 arried out such genetic analyses with a large sample size and identified\n
 cis- and trans-acting polymorphic regulators for about 1\,000 human genes.
  We\nvalidated the cis-acting regulators by demonstrating differential all
 elic\nexpression with sequencing of transcriptomes (RNA-Seq) and the\ntran
 s-regulators by gene knockdown\, metabolic assays\, and chromosome\nconfor
 mation capture analysis. The majority of the regulators act in trans\nto t
 he target (regulated) genes. Most of these trans-regulators were not\nknow
 n to play a role in gene expression regulation. The identification of\nthe
 se regulators enabled the characterization of polymorphic regulation of\nh
 uman gene expression at a resolution that was unattainable in the past.\n\
 nAuthor Summary\n\nCellular characteristics and functions are determined l
 argely by gene\nexpression and expression levels differ among individuals\
 , however it is not\nclear how these levels are regulated. While many cis-
 acting DNA sequence\nvariants in promoters and enhancers that influence ge
 ne expression have been\nidentified\, only a few polymorphic trans-regulat
 ors of human genes are\nknown. Here\, we used human B-cells from individua
 ls belonging to large\nfamilies and identified polymorphic trans-regulator
 s for about 1\,000 human\ngenes. We validated these results by gene knockd
 own\, metabolic perturbation\nstudies and chromosome conformation capture 
 assays. Although these\nregulatory relationships were identified in cultur
 ed B-cells\, we show that\nsome of the relationships were also found in pr
 imary fibroblasts. The large\nnumber of regulators allowed us to better un
 derstand gene expression\nregulation\, to uncover new gene functions\, and
  to identify their roles in\ndisease processes. This study shows that gene
 tic variation is a powerful\ntool not only for gene mapping but also to st
 udy gene interaction and\nregulation.\n\nNOTE THE ROOM CHANGE!\n\n-- 009 i
 nstead of 132 --
LOCATION:Room 009\, CRI
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