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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-09

AUTHORS

Calliope A Dendrou, Vincent Plagnol, Erik Fung, Jennie H M Yang, Kate Downes, Jason D Cooper, Sarah Nutland, Gillian Coleman, Matthew Himsworth, Matthew Hardy, Oliver Burren, Barry Healy, Neil M Walker, Kerstin Koch, Willem H Ouwehand, John R Bradley, Nicholas J Wareham, John A Todd, Linda S Wicker

ABSTRACT

Genome-wide association studies (GWAS) have identified over 300 regions associated with more than 70 common diseases. However, identifying causal genes within an associated region remains a major challenge. 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. 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. More... »

PAGES

1011-1015

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.434

DOI

http://dx.doi.org/10.1038/ng.434

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016741965

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19701192


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