Dissemin is shutting down on January 1st, 2025

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Nature Research, Nature Genetics, 9(41), p. 1011-1015, 2009

DOI: 10.1038/ng.434

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Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

Genome-wide association (GWA) studies have identified over 300 regions associated with more than 70 common diseases1. However, identifying causal genes within an associated region remains a major challenge1,2. 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 interleukin-2 (IL-2) receptor alpha-chain (IL-2RA, or CD25) protein are restricted to particular immune cell types and correlate with several haplotypes in the IL2RA region that have previously been associated to the autoimmune diseases type 1 diabetes (T1D) and multiple sclerosis2-4. 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-GWA gene-phenotype investigations, and demonstrate the usefulness of a large bioresource of genotype-selectable normal donors from whom fresh, primary cells can be analyzed.