Fine mapping of type 1 diabetes regions Idd9.1 and Idd9.2 reveals genetic complexity

Hamilton-Williams, Emma E., Rainbow, Daniel B., Cheung, Jocelyn, Christensen, Mikkel, Lyons, Paul A., Peterson, Laurence B., Steward, Charles A., Sherman, Linda A. and Wicker, Linda S. (2013) Fine mapping of type 1 diabetes regions Idd9.1 and Idd9.2 reveals genetic complexity. Mammalian Genome, 24 9-10: 358-375. doi:10.1007/s00335-013-9466-y


Author Hamilton-Williams, Emma E.
Rainbow, Daniel B.
Cheung, Jocelyn
Christensen, Mikkel
Lyons, Paul A.
Peterson, Laurence B.
Steward, Charles A.
Sherman, Linda A.
Wicker, Linda S.
Title Fine mapping of type 1 diabetes regions Idd9.1 and Idd9.2 reveals genetic complexity
Formatted title
Fine mapping of type 1 diabetes regions Idd9.1 and Idd9.2 reveals genetic complexity
Journal name Mammalian Genome   Check publisher's open access policy
ISSN 0938-8990
1432-1777
Publication date 2013-10
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s00335-013-9466-y
Volume 24
Issue 9-10
Start page 358
End page 375
Total pages 18
Place of publication New York, United States
Publisher Springer
Collection year 2014
Language eng
Formatted abstract
Nonobese diabetic (NOD) mice congenic for C57BL/10 (B10)-derived genes in the Idd9 region of chromosome 4 are highly protected from type 1 diabetes (T1D). Idd9 has been divided into three protective subregions (Idd9.1, 9.2, and 9.3), each of which partially prevents disease. In this study we have fine-mapped the Idd9.1 and Idd9.2 regions, revealing further genetic complexity with at least two additional subregions contributing to protection from T1D. Using the NOD sequence from bacterial artificial chromosome clones of the Idd9.1 and Idd9.2 regions as well as whole-genome sequence data recently made available, sequence polymorphisms within the regions highlight a high degree of polymorphism between the NOD and B10 strains in the Idd9 regions. Among numerous candidate genes are several with immunological importance. The Idd9.1 region has been separated into Idd9.1 and Idd9.4, with Lck remaining a candidate gene within Idd9.1. One of the Idd9.2 regions contains the candidate genes Masp2 (encoding mannan-binding lectin serine peptidase 2) and Mtor (encoding mammalian target of rapamycin). From mRNA expression analyses, we have also identified several other differentially expressed candidate genes within the Idd9.1 and Idd9.2 regions. These findings highlight that multiple, relatively small genetic effects combine and interact to produce significant changes in immune tolerance and diabetes onset.
Keyword Cd4 T-cells
Nod mice
Pi3K/pten/akt/mtor pathway
Laboratory mouse
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
 
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