Samples were in all cases obtained from subjects under informed consent of parents and with IRB/Ethics Board approval. Each center was allowed to develop its own genotyping methods as long as a minimum accuracy of 98% was achieved. Five HLA screening laboratories were chosen for TEDDY screening and they employed four different genotyping strategies. Screening genotyping results were expected to be available by the time the infant was 2 months of age. Low-cost genotyping was achieved by adopting a two-stage screening strategy in four laboratories. In the first stage, approximately 90% of the ineligible subjects are excluded by the presence of specific alleles that can be detected inexpensively. In the second stage, detailed genotyping of DQB1 and DQA1 or DQB1 and DRB1 alleles are determined. For the general population, the DRB1*0403 allele is usually determined by a restriction digest of the exon 2 amplicon. The first-stage strategy used by the Finnish and Swedish screening laboratories was to exclude certain resistant alleles while requiring certain susceptible alleles, and was previously described [15 (link)]. The WAS laboratory used a first-stage strategy of exclusion of DQB1*05, DQB1*06, DQB1*0301 and DQA1*02 followed by direct exon 2 sequencing of specific DQB1 and DQA1 alleles in the second stage genotyping. The GEO screening laboratory excluded subjects with DQB1*05, DQB1*06 and DQB1*0301 using allele-specific amplifications in the first stage. The potentially eligible subjects were further genotyped for DQB1 by denaturing gradient gel electrophoresis using a previously published protocol [9 (link)] and DRB1 by Luminex beads. Samples from the COL center were genotyped in the laboratory of Dr. Erlich using a reverse line blot SSOP technique with a panel of immobilized probes for DRB1 and DQB1 alleles [11 (link)]. The same laboratory also served as the TEDDY HLA Reference Laboratory to carry out confirmatory tests of enrolled subjects from all six clinical centers using separate DRB1, DQA1 and DQB1 reverse line blots, each with a much higher resolution panel of immobilized probes [16 (link)].