No evidence for SEL1L as a candidate gene for IDDM11‐conferred susceptibility

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Abstract
Background The SEL1L gene is located on human chromosome 14q24.3‐31 close to D14S67 which has been previously proposed to be a type 1 diabetes mellitus locus (IDDM11). Sel‐1 is a negative regulator of the Notch signalling pathway and SEL1L is selectively expressed in adult pancreas and islets of Langerhans. This suggests that SEL1L may be a candidate gene for IDDM11. Methods We have analysed two newly identified CA‐repeat polymorphisms within the genomic sequence of the SEL1L locus for association with type 1 diabetes mellitus (T1DM) in 152 Danish T1DM‐affected sib‐pair families and in 240 Sardinian families (229 simplex and 11 sib‐pair families). Results No evidence for association of the two SEL1L markers with T1DM was observed in either the Danish or the Sardinian families. We have also used allelic sharing methods to analyse linkage with T1DM in the IDDM11 region using the same markers and the Danish collection of affected sib‐pair families. No evidence of linkage was observed (Zmax=0.86). Conclusion Although several lines of evidence suggest that SEL1L might be a candidate for IDDM11‐conferred susceptibility to T1DM the present study does not support this hypothesis. Copyright © 2001 John Wiley & Sons, Ltd.