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SUMMARY:Using three-dimensional chromatin structure to understand autoimmu
 ne disease mechanisms - Dr Olly Burren\, Research Associate\, Department o
 f Medicine
DTSTART:20161202T140000Z
DTEND:20161202T150000Z
UID:TALK69553@talks.cam.ac.uk
CONTACT:Katja Kivinen
DESCRIPTION:Through genome wide association studies (GWAS) over 320 distin
 ct loci have been robustly associated with autoimmune disease susceptibili
 ty. Candidate causal variants are enriched in regulatory regions\, but con
 necting these regulatory variants to target genes within relevant tissue c
 ontexts has proved challenging. In this talk I will describe one such appr
 oach for linking variants with the genes they regulate by mapping physical
  chromosome contacts\, through the use of promoter capture Hi-C (PCHi-C). 
 By the application of novel statistical methods which combine GWAS dataset
 s with chromatin contact maps for 17 primary human blood cells\, we were a
 ble to prioritise putative disease mechanisms for functional validation. T
 o support our approach\, we found evidence for allelically imbalanced tran
 scription of IL2RA within CD4 + T cells of individuals heterozygous for PC
 Hi-C linked autoimmune-associated variants. This allelic imbalance is spec
 ific to non-activated cells\, reflecting the predicted effect of context-s
 ensitive chromatin interactions.\n
LOCATION:Seminar Room\, Strangeways Research Laboratory
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