Tdmq1^DBA/2
QTL Variant Detail

Summary

• QTL variant: Tdmq1^DBA/2
• Name: type 2 diabetes modifying QTL 1; DBA/2
• MGI ID: MGI:3579353
• QTL: Tdmq1 Location: Chr9:40419594-51808670 bp Genetic Position: Chr9, cM position of peak correlated region/allele: 25.36 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased blood glucose concentration compared to BKS. (J:97535)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:97535

Linkage analysis was performed on 113 female animals from a (DBA/2 x BKS.Cg M +/+ Lepr^db)F2 intercross to identify modifying loci for type 2 diabetes. All animals evaluated were homozygous for the Lep2^db mutation. Phenotypes evaluated for type 2 diabetes were body weight, blood glucose concentration at different timepoints of the glucose tolerance test, and parametrial fat pad weight. Homozygous mutant F2 animals exhibited significantly greater body weight, blood glucose concentration, and parametrial fat pad weights compared to parental strain BKS.Cg M +/+ Lepr^db. Genome scan of the F2 population with 227 microsatellite markers revealed linkage to a 10 Mb region on mouse Chromosome 9 between D10Mit198 (26 cM) and D9Mit206 (29 cM) for body weight (LOD=3.35), parametrial fat pad weight (LOD=4.22), and blood glucose at 120 minutes (LOD=5.67). Peak linkage occurred around D9Mit93 (27 cM). This locus is named Tdmq1 (type 2 diabetes modifying QTL 1). Animals homozygous for DBA/2-derived alleles at Tdmq1exhibit increased blood glucose at 120 minutes compared to animals homozygous for BKS-derived alleles. In addition, animals homozygous for BKS-derived alleles at Tdmq1 exhibit increased body weight and parametrial fat pad weights compared to animals homozygous for DBA/2-derived alleles.

Candidate genes for Tdmq1 were screened using gene expression QTL (eQTL) analysis. Out of 76 known genes found within the Tdmq1 QTL interval, 15 showed differential expression between DBA/2 and BKS.Cg M +/+ Lepr^db. Expression levels of these 15 genes were then evaluated in the F2 population. Four genes showed correlation to mRNA expression and the Tdmq1 locus. D930028F11Rik showed linkage to expression in parametrial fat pads (LOD=7.29) and soleus muscle (LOD=35.21), Nnmt showed linkage to expression in parmetrial fat pads (LOD=4.46), Cryab showed linkage to expression in parametrial fat pads (LOD=12.26), and 4432416J03Rik showed linkage to expression in liver (LOD=4.72) and soleus muscle (LOD=7.14). All four candidate genes showed increased mRNA expression with the BKS-derived allele.

SNP analysis of candidate genes was also performed. Results indicated that 4432416J03Rik exhibits the greatest number of amino acid variations between BKS and DBA/2.

A previously identified obesity QTL mapping near Tdmq1 is Obq5 at 19 cM. Interestingly, the Tdmq1 interval is syntenic to a region on human Chromosome 11q23 linked to type 2 diabetes or obesity in Pima Indians.

References

• Original: J:97535 Yaguchi H, et al., Identification of candidate genes in the type 2 diabetes modifier locus using expression QTL. Genomics. 2005 May;85(5):591-9
• All: 1 reference(s)