Abstract
BackgroundA genome-wide search for genes that predispose to type 1 diabetes using linkage analysis was performed using 900 microsatellite markers in 70 nuclear families with affected siblings from Finland, a population expected to be more genetically homogeneous than others, and having the highest incidence of type 1 diabetes in the world and, yet, the highest proportion in Europe of cases (10%) carrying neither of the highest risk HLA haplotypes that include DR3 or DR4 alleles.ResultsIn addition to the evidence of linkage to the HLA region on 6p21 (nominal p = 4.0 × 10-6), significant evidence of linkage in other chromosome regions was not detected with a single-locus analysis. The two-locus analysis conditional on the HLA gave a maximum lod score (MLS) of 3.1 (nominal p = 2 × 10-4) on chromosome 9p13 under an additive model; MLS of 2.1 (nominal p = 6.1 × 10-3) on chromosome 17p12 and MLS of 2.5 (nominal p = 2.9 × 10-3) on chromosome 18p11 under a general model.ConclusionOur genome scan data confirmed the primary contribution of the HLA genes also in the high-risk Finnish population, and suggest that non-HLA genes also contribute to the familial clustering of type 1 diabetes in Finland.
Highlights
A genome-wide search for genes that predispose to type 1 diabetes using linkage analysis was performed using 900 microsatellite markers in 70 nuclear families with affected siblings from Finland, a population expected to be more genetically homogeneous than others, and having the highest incidence of type 1 diabetes in the world and, yet, the highest proportion in Europe of cases (10%) carrying neither of the highest risk HLA haplotypes that include DR3 or DR4 alleles
The highest maximum lod score (MLS) was at chromosome 6p21, the HLA region where the major type 1 diabetes susceptibility gene(s) locates
For the two-locus analysis, we fixed markers with highest MLS at the HLA region to adjust for the effect of HLA
Summary
A genome-wide search for genes that predispose to type 1 diabetes using linkage analysis was performed using 900 microsatellite markers in 70 nuclear families with affected siblings from Finland, a population expected to be more genetically homogeneous than others, and having the highest incidence of type 1 diabetes in the world and, yet, the highest proportion in Europe of cases (10%) carrying neither of the highest risk HLA haplotypes that include DR3 or DR4 alleles. The observation of familial clustering of type 1 diabetes suggests that genetic factors are involved in the etiology of type 1 diabetes. Type 1 diabetes is about 15 times (6/0.4) more common in siblings of type 1 diabetic patients than in the general population. The high discordance between MZ twins, suggests that the penetrance of the type 1 susceptibility genes is low
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
