Combining mouse congenic strains and microarray gene expression analyses to study a complex trait: the NOD model of type 1 diabetes.

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 the Idd9.

Parameters for reliable results in genetic association studies in common disease.

It is increasingly apparent that the identification of true genetic associations in common multifactorial disease will require studies comprising thousands rather than the hundreds of individuals employed to date. Using 2,873 families, we were unable to confirm a recently published association of the interleukin 12B gene in 422 type I diabetic families. These results emphasize the need for large datasets, small P values and independent replication if results are to be reliable.