Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Combining congenic mapping with microarray expression profiling offers an opportunity to establish functional links between genotype and phenotype for complex traits such as type 1 diabetes (T1D). We used high-density oligonucleotide arrays to measure the relative expression levels of >39,000 genes and ESTs in the NOD mouse (a murine model of T1D and other autoimmune conditions), four NOD-derived diabetes-resistant congenic strains, and two nondiabetic control strains. We developed a simple, yet general, method for measuring differential expression that provides an objective assessment of significance and used it to identify >400 gene expression differences and eight new candidates for theIdd9.1locus. We also discovered a potential early biomarker for autoimmune hemolytic anemia that is based on different levels of erythrocyte-specific transcripts in the spleen. Overall, however, our results suggest that the dramatic disease protection conferred by sixIddloci (Idd3,Idd5.1, Idd5.2, Idd9.1, Idd9.2, andIdd9.3) cannot be rationalized in terms of global effects on the noninduced immune system. They also illustrate the degree to which regulatory systems appear to be robust to genetic variation. These observations have important implications for the design of future microarray-based studies in T1D and, more generally, for studies that aim to combine genome-wide expression profiling and congenic mapping.[The supplemental research data accompanying this article are available through the authors' web site (http://www-gene.cimr.cam.ac.uk/todd/), and the array data have been submitted to the GEO data repository (http://www.ncbi.nlm.nih.gov/geo/) under accession no. GSE11]

Original publication

DOI

10.1101/gr.214102

Type

Journal article

Journal

Genome Research

Publisher

Cold Spring Harbor Laboratory

Publication Date

01/02/2002

Volume

12

Pages

232 - 243