Dendrou, CA and Plagnol, V and Fung, E and Yang, JHM and Downes, K and Cooper, JD and Nutland, S and Coleman, G and Himsworth, M and Hardy, M and Burren, O and Healy, B and Walker, NM and Koch, K and Ouwehand, WH and Bradley, JR and Wareham, NJ and Todd, JA and Wicker, LS (2009) Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource. NAT GENET , 41 (9) 1011 - U80. 10.1038/ng.434.
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Genome-wide association studies (GWAS) have identified over 300 regions associated with more than 70 common diseases(1). However, identifying causal genes within an associated region remains a major challenge(1,2). One approach to resolving causal genes is through the dissection of gene-phenotype correlations. Here we use polychromatic flow cytometry to show that differences in surface expression of the human interleukin-2 (IL-2) receptor alpha (IL2RA, or CD25) protein are restricted to particular immune cell types and correlate with several haplotypes in the IL2RA region that have previously been associated with two autoimmune diseases, type 1 diabetes (T1D) and multiple sclerosis(2-4). We confirm our strongest gene-phenotype correlation at the RNA level by allele-specific expression (ASE). We also define key parameters for the design and implementation of post-GWAS gene-phenotype investigations and demonstrate the usefulness of a large bioresource of genotype-selectable normal donors from whom fresh, primary cells can be analyzed.
|Title:||Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource|
|Keywords:||REGULATORY T-CELLS, NOD MICE, DIABETES-MELLITUS, ALLELIC VARIANTS, HUMAN IMMUNOLOGY, RNA-SEQ, INTERLEUKIN-2, IL-2, RECEPTOR, DISEASE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment > UCL Genetics Institute|
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