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WED 139 Gene expression regulation in CD4+ t-cell dysfunction in ms
  1. Hrastelj James,
  2. Bray Nicholas,
  3. Williams Nigel,
  4. Robertson Neil
  1. Cardiff


Background Genetic risk variants for complex disorders such as multiple sclerosis (MS) rarely encode protein. Growing evidence suggests risk variants regulate gene expression in specific disease-relevant cells by altering regulatory genetic sequences. This can be explored by correlating genotype at risk loci with expression of nearby genes (cis-regulation), with greatest sensitivity demonstrated in the most relevant cell types. Identifying genes under regulation by the MS risk variants could be a crucial step in identifying novel therapeutic targets.

Aims 1) Interrogate MS risk loci for cis-regulatory effects using allele-specific expression (ASE) analysis. 2) Establish a publicly available resource of genome-wide RNA-seq expression data in CSF-derived CD4 +T lymphocytes. 3) Correlate gene expression data with longitudinal clinical data to seek biomarkers of prognosis.

Method and progress We have extracted RNA from FACS-sorted CSF-derived CD4 +T lymphocytes from over 100 individuals. cDNA library preparation and sequencing for each sample is underway.

Data analysis ASE analysis makes use of a pre-selected transcribed SNP to differentiate maternal and paternal transcripts of each gene of interest. When an individual is heterozygous at an additional functional regulatory locus the ratio of maternal: paternal expression will deviate from 1:1. Each MS risk locus will be interrogated for this effect.

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