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Partial exclusion mapping of the nonobese (NOD) diabetic mouse genome has shown linkage of diabetes to at least five different chromosomes. We have now excluded almost all of the genome for the presence of susceptibility genes with fully recessive effects and have obtained evidence of linkage of ten distinct loci to diabetes or the prediabetic lesion, insulitis, indicative of a polygenic mode of inheritance. The relative importance of these loci and their interactions have been assessed using a new application of multiple polychotomous regression methods. A candidate disease gene, interleukin-2 (Il-2), which is closely linked to insulitis and diabetes, is shown to have a different sequence in NOD, including an insertion and a deletion of tandem repeat sequences which encode amino acid repeats in the mature protein.

Original publication

DOI

10.1038/ng0893-404

Type

Journal article

Journal

Nat Genet

Publication Date

08/1993

Volume

4

Pages

404 - 409

Keywords

Amino Acid Sequence, Animals, Autoimmune Diseases, Base Sequence, Chromosome Mapping, Crosses, Genetic, DNA, Complementary, Diabetes Mellitus, Type 1, Female, Genetic Linkage, Genetic Markers, Interleukin-2, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Molecular Sequence Data, Oligodeoxyribonucleotides, Pancreatic Diseases, Regression Analysis