Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  1
• Reference
  J:134171 Chen Y, et al., Variations in DNA elucidate molecular networks that cause disease. Nature. 2008 Mar 27;452(7186):429-35
• ID
  MGI:3790705

Genes

Gene	Assay Type
Apcs	other
F11r	other
Rgs5	other
Usf1	other
Metpq	visible phenotype

Notes

• Experiment
  Suggestive linkage to gonadal fat mass was previously mapped to distal mouse Chromosome 1 at 64 cM (Wang et al, 2006. J:115779) using an F2 intercross between C57BL/6J-Apoe^tm1Unc and C3H/HeJ-Apoe^tm1Unc parental strains. Analysis of BXH (B=C57BL/6J; H=C3H/HeJ) recombinant inbred strains indicates this locus is linked to 8 different metabolic parameters: glucose, aortic lesions, free fatty acids, abdominal fat, total plasma cholesterol, plasma HDL cholesterol, weight and triglycerides. The presence of Apoa2 partially explains the glucose pheontypes and the presence of Tnfsf4 (formerly QTL Ath1) was not linked to any of the phenotypes. This suggests other genes/QTLs on distal chromosome 1 have a pleiotropic effect on 8 metabolic phenotypes. This locus displays peak linkage at approximately 170 Mb on mouse Chromosome 1 and is named Metpq (metabolic phenotypes QTL).
  
  Several liver cis-eQTLs co-localize with Metpq including expression of Usf1 (93.3 cM), F11r (93.3 cM), Apcs (94.2 cM) and Rgs5 (86.5 cM). These genes are possible candidates for Metpq on chromosome 1. Usf1 and F11r have been implicated in familial combined hypercholesterolemia and Apcs is associated with atherosclerotic lesion formation. In addition, the Rgs5 eQTL shows the strongest association with Metpq metabolic phenotypes and is associated with human hypertension and atherosclerotic plaque components.
  
  Analysis of a macrophage network of genes identified novel trans relationships between Lpl (chr8, 33 cM), Lactb (chr9) and Ppm1l (chr3) and the chromosome 1 metabolic phenotypes. In vivo analysis of mutant animals validated the role of these genes in metabolic phenotypes. Lpl^tm1Ijg heterozygous animals and FVB-Tg(Lactb)1Lus transgenic animals display significantly increased fat-to-lean-mass ratios compared to wild type controls. Ppm1l^tm1Dgen knockout animals display significantly increased body weight, fat mass, blood pressure, decreased free fatty acids and insulin dysfunction compared to control animals.