Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  1
• Reference
  J:143549 Hunter K, et al., Interactions between Idd5.1/Ctla4 and other type 1 diabetes genes. J Immunol. 2007 Dec 15;179(12):8341-9
• ID
  MGI:3830855

Genes

Gene	Assay Type
Idd5.1	resistance/susceptibility
D1Mit249	PCR amplified length variant
Idd5.2	resistance/susceptibility
Idd5.3	resistance/susceptibility
Idd5.4	resistance/susceptibility

Notes

• Experiment
  A series of subcongenic lines derived from C57BL/10J-derived donor DNA on a NOD/MrkTac genetic background was used to refine Idd5 (insulin dependent diabetes 5) on mouse Chromosome 1 into four separate QTLs- Idd5a, Idd5b, Idd5c and Idd5d. Donor strain C57BL/10J is resistant to type 1 diabetes mellitus compared to background strain NOD/MrkTac. The 4 QTLs that comprise the Idd5 locus display interactive effects. C57BL/10J alleles at Idd5a, Idd5b and Idd5c confer diabetes resistance while the same alleles at Idd5d confer diabetes susceptibility.
  
  Idd5a (insulin dependent diabetes 5a) was localized to a 2 Mb region between D1Mit249 (32.8 cM; 60.8 Mb) and genetic sequence AL671560GA near Pard3b and Nrp2 (62.7 Mb). Ctla4 (30.1 cM; 60.9 cM) was named a likely candidate gene for Idd5a due to the presence of sequence variations and gene expression and splice isoform differences between C57BL/10J and NOD/MrkTac. C57BL/10J-derived diabetes resistance alleles at Idd5a have the strongest effect when C57BL/10J allelesare also present at Idd5b, Idd5c and Idd5d.
  
  Idd5b (insulin dependent diabetes 5b) mapped to a 1.5 Mb interval where Slc11a1 (formerly Nramp1, 39.2 cM; 74.4 Mb) was named a likely candidate gene. Interaction between Idd5b and Idd3 on chromosome 4 was previously noted. C57BL/10J-derived alleles at Idd5b and Idd3 confer reduced insulitis, but do not confer diabetes resistance.
  
  A novel diabetes resistance locus named Idd5c (insulin dependent diabetes 5c) was identified between rs30280887 (66.5 Mb) and rs30471359 (70.08 Mb). Eleven genes map to this 3.5 Mb interval of which Acadl (27.3 cM; 66.87 Mb) and Ikzf2 (69.58 Mb) are potential candidates for Idd5c. C57BL/10J-derived alleles at Idd5c are required for nearly complete protection from diabetes when resistance alleles are also present at Idd5a and Idd3 on mouse Chromosome 3 (19.2 cM; 60.2 Mb). It is unclear if the presence of Idd5c and Idd3 are sufficient to mediate diabetes resistance; however, congenic lines carrying both loci are now under constructionto resolve this issue.
  
  Idd5d (insulin dependent diabetes 5d) mapped to the distal portion of the Idd5 locus from approximately 76 Mb to 160 Mb. An intervening NOD/MrkTac-derived interval in Idd5d is located from approximately 140 Mb to 150 Mb due to a double recombination event in a progenitor congenic line. C57BL/10J-derived alleles at Idd5d confer diabetes susceptibility even when resistance alleles are present at Idd5b and Idd5c.