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Updated: Jul 31, 2026
10:17
An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
Published on: November 3, 2010
Type 1 diabetes and the OAS gene cluster: association with splicing polymorphism or haplotype?
M-C Tessier1, H-Q Qu, R Fréchette
1Endocrine Genetics Laboratory, The McGill University Health Center, Montreal Children's Hospital, Montréal, Québec, Canada.
Journal of Medical Genetics
|July 15, 2005
Summary
The OAS1 gene variant rs10774671 is linked to type 1 diabetes (T1D). However, a different OAS1 gene variant, a serine/glycine substitution, is more likely the true cause of T1D in this case.
Area of Science:
- Genetics
- Immunology
- Endocrinology
Background:
- The 2',5'-oligoadenylate synthetase (OAS1) gene family is crucial for innate antiviral immunity.
- A specific OAS1 single nucleotide polymorphism (SNP), rs10774671, has been associated with increased enzyme activity and type 1 diabetes (T1D).
Purpose of the Study:
- To confirm the association between the OAS1 SNP rs10774671 and T1D.
- To investigate whether rs10774671 is the functional variant responsible for the observed T1D association.
Main Methods:
- Transmission disequilibrium test (TDT) was used to analyze T1D association in 784 nuclear families.
- Genotyping of two non-synonymous SNPs in OAS1 exons 3 and 7 was performed to assess linkage disequilibrium.
Main Results:
- The T1D association with rs10774671 was confirmed (p = 0.033).
- Significant transmission distortion was observed for haplotypes not carrying the minor allele at rs10774671, indicating linkage disequilibrium.
- A serine/glycine substitution in OAS1 exon 3 showed significant transmission distortion.
Conclusions:
- The T1D association with rs10774671 is confirmed but likely not solely due to the splicing effect of this SNP.
- A non-synonymous variant in OAS1 exon 3 is a more probable functional driver of T1D susceptibility.
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