Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  4
• Reference
  J:237152 Suto J, et al., Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the A(y) allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss. BMC Genet. 2013 May 04;14:35
• ID
  MGI:5910613

Genes

Gene	Assay Type
Bw25q2	visible phenotype
Zfp69
Bmiq13	visible phenotype

Notes

• Experiment
  Mice carrying the A^y allele at the agouti locus become obese and are heavier than their non-A^y littermates. However, this does not hold true for the genetic background of the DDD/SgnRbrc (DDD) mouse strain. At 22 weeks of age, DDD.Cg-A^y females are heavier than DDD females, whereas DDD.Cg-A^y males are lighter than DDD males. The aim of the current study was to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-A^y males.
  
  Four week old F1 mice produced from (DDD/SgnRbrc x C57BL/6J-A^y) and (C57BL/6J x DDD/SgnRbrc-A^y) crosses, and their non agouti littermates, were subject to weekly body weight measurements from 5 to 25 weeks of age. At 25 weeks of age, mice were euthanized after they were fasted for 4 hours and whole blood was drawn from the heart and blood glucose levels (BGLC) were determined. The liver, pancreas, and adipose tissues were removed at necropsy from parental strains of both the sexes. Body length was defined as the anal-nasal length. Body mass index (BMI) was calculated and used to estimate the degree of obesity.
  
  QTL mapping analysis was conducted to identify genes possibly associated with the lower body weight of DDD-A^y males. 196 backcrossed male mice were generated from a backcross of (DDD x (C57BL/6J x DDD-A^y)F1) mice. One hundred were agouti and 96 were non-agouti.
  
  QTL analysis was conducted using R/qtl. Threshold logarithm of odds (LOD) scores for suggestive (P < 0.63) and significant (P < 0.05) linkages were determined by performing 1,000 permutations for each trait. For significant QTLs, 95% CI was defined by a decline of 1.5 LOD. QTL analyses were conducted for body weight (from 5 to 25 weeks of age), BMI, and BGLC, plasma glucose (PGLC), cholesterol (CHO), triglyceride (TG), and HMW adiponectin levels using the results of 100 backcrossed A^y males.
  
  Tables 5 and 7:
  
  QTL Bw25q1 (body weight at 25 weeks QTL 1) mapped to Chromosome 1 with a LOD score of 2.69 nearest marker D1Mit102 at 147.25 Mb with a 95% CI spanning from 106.49 to 188.44 Mb. The B6 allele was the high allele at this locus with the DDD allele associated with a lower body weight. A proposed candidate gene mapping within the CI at 173.96 Mb was Ifi202b.
  
  QTL Bw25q2 (body weight at 25 weeks QTL 2) mapped to Chromosome 4 with a LOD score of 4.25 nearest marker D4Mit234 at 145.06 Mb with a 95% CI spanning from 112.44 to 151.57 Mb. The B6 allele was the high allele at this locus with the DDD allele associated with a lower body weight. A proposed candidate gene mapping within the CI at 120.93 Mb was Zfp69.
  
  A significant QTL for body mass index mapped to Chromosome 4. QTL Bmiq13 (body mass index QTL 13) peaked at 55 cM nearest marker D4Mit234 with a LOD score of 4.77. The 95% CI spanned from 36 to 61 cM.. The B6 allele was the high allele at Bmiq13
  
  Suggestive QTL for HMW adiponectin, BGLG, PGLC levels were colocalized with the QTL for body weight on chromosome 4 but not with the QTL on chromosome 1. The DDD allele was associated with increased BGLC and PGLC levels and decreased HMW adiponectin levels.
  Additional suggestive QTL were listed on Table 5.
  
  When backcrossed A^y and non-A ^y males were combined and reanalyzed using the agouti locus genotype (A^y or non-A^y) as a covariate, significant evidence (LOD=3.52 at 61 cM) of a QTL covariate interaction was identified for the QTL on chromosome 4 but not for the QTL on chromosome 1.