Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  19
• Reference
  J:100832 Collin GB, et al., Genetic modifiers interact with Cpefat to affect body weight, adiposity, and hyperglycemia. Physiol Genomics. 2005 Jul 14;22(2):182-90
• ID
  MGI:3707853

Genes

Gene	Assay Type
Find1	visible phenotype
D19Mit66	PCR amplified length variant

Notes

• Experiment
  Linkage analysis was performed using 282 male Cpe^fat homozygous animals from a (BKS.HRS-Cpe^fat x HRS/J)F2 intercross to identify modifiers of Cpe^fat. A panel of 87 polymorphic markers at an average spacing of 20 cM was used for the genome scan. TheCpe^fat mutation results in severe obesity, hyperinsulinemia, and hyperglycemia on a C57BLKS/J genetic background. However, when Cpe^fat is on a HRS/J genetic background, animals are moderately obese and display hyperinsulinemia without hypoglycemia. F2animals were weighed once a month and blood was collected bi-weekly until sacrifice at 24 or 30 weeks of age.
  
  Significant linkage to adiposity mapped to 31 cM on mouse Chromosome 11 near D11Mit242 and is named Fina1 (fat induced adiposity 1). This locusis also associated with body weight and weight gain. The QTL interval spans approximately 15 cM - 50 cM. Homozygosity for C57BLKS/J-derived alleles at Fina1 confers increased adiposity and increased weight gain. Hcrt (61.2 cM) and Cpd (46 cM) are potential candidate genes for Fina1. Hcrt and Cpd coding sequence and mRNA abundance did not differ between HRS/J and C57BLKS/J strains.
  
  Bwt1 (body weight 1) mapped to 22 cM on mouse Chromosome 14 near Hr and D14Mit5. The QTL interval spans approximately15cM - 45 cM. This locus appears to act independently of the Cpe^fat mutation. The Hr^hr mutation segregates with the body weight phenotype and is therefore a possible candidate gene. F2 animals homozygous for Hr^hr display significantly decreased bodyweight.A locus at 47 cM on chromosome 18 interacts with Bwt1 to decrease body weight. Animals homozygous for HRS/J-derived alleles at Bwt1 and heterozygous at D18Mit79 display significantly lower body weight compared to other genotypes. Homozygous HRS/J-derivedalleles at Bwt1 also interact with homozygous C57BLKS/J-derived alleles at Find1 (chr19) to increase plasma glucose levels.
  
  Find1 (fat induced diabetes 1) mapped to 41 cM on mouse Chromosome 19 near D19Mit66. The QTL interval spans 20 cM - 50 cM. HRS/J-derived alleles at Find1 confer increased plasma glucose. This locus interacts with Bwt1 on chromosome 14 to increase plasma glucose levels. (See above.) Previously identified diabetes QTLs Tanidd1 (50 cM) and T2dm2 (53 cM) are in the vicinity of Find1.
  
  Find2 (fat induced diabetes 2) mapped to 68 cM on mouse Chromosome 5 near D5Mit95. This locus is associated with plasma glucose, plasma insulin, and plasma cholesterol levels. The QTL interval spans approximately 35 cM - 90 cM. Homozygosity for C57BLKS/J-derived alleles at Find2 confers increased plasma glucose, increased plasma total cholesterol, and decreased plasma insulin.