Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  1
• Reference
  J:90924 Wicker LS, et al., Fine mapping, gene content, comparative sequencing, and expression analyses support Ctla4 and Nramp1 as candidates for Idd5.1 and Idd5.2 in the nonobese diabetic mouse. J Immunol. 2004 Jul 1;173(1):164-73
• ID
  MGI:3046323

Genes

Gene	Assay Type
Idd5.1	resistance/susceptibility
D1Mit74	PCR amplified length variant
D1Mit249	PCR amplified length variant
Cd28	reported elsewhere
Ctla4	reported elsewhere
Nrp2	reported elsewhere
Pard3b	reported elsewhere
Idd5.2	resistance/susceptibility
D1Mit180	PCR amplified length variant
D1Mit46	PCR amplified length variant
Slc11a1	reported elsewhere

Notes

• Experiment
  In this study the Idd5a interval was refined to 30.1 cM - 32.8 cM in subcongenic animals carrying C57BL/10J-derived DNA from D1Mit74 to D1Mit249 on an NOD genetic background. Parental strain NOD/MrkTac is susceptible to diabetes whereas parental strain C57BL/10J is resistant. Cd28, Casp8, and Cflar were eliminated as candidate genes as a result. Ctla4 (30.1 cM) and Icos (32 cM) remain strong candidate genes while 2810455B10Rik (Als2cr19) and Nrp2 are considered possible candidate genes. A recombination coldspot was observed between D1Mit249 and D1Mit303 as this distance is 2 Mb and only 3 recombination events occurred out of 22 expected.
  
  A high amount of sequence polymorphism between C57BL/6J and NOD/MrkTac was observed within the reduced Idd5a interval. Several SNPs were observed in the intronic and 3' and 5' regulatory sequences of Ctla4 and Icos as well as 1 exonic SNP for each gene. Very few SNPs were observed for 2810455B10Rik. Differential expression of a Ctla4 splice isoform (liCTLA-4 mRNA) was observed for animals carrying the Idd5a^C57BL/10/J allele vs animals carrying the Idd5a^NOD/MrkTac allele. The Idd5a interval is syntenic to human Chromosome 2q33.3-q34.
  
  The Idd5b interval was refined to a 1.52 Mb region between D1Mit180 (41 cM) and D1Mit46 (43.1 cM) using subcongenic lines designated R193 and R444s. 45 genes map to this interval. Scl11a1 (Nramp1) is a candidate gene for Idd5b and contains a functional polymorphism between C57BL/6J, C57BL/10J, and NOD/MrkTac. The Idd5b interval is syntenic to human Chromosome 2q35.
  
  The presence of both Idd5a and Idd5b are required for full diabetes resistance. Each locus alone offers partial protection.