Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  2
• Reference
  J:135073 Doorenbos C, et al., Quantitative Trait Loci for Urinary Albumin in Crosses Between C57BL/6J and A/J Inbred Mice in the Presence and Absence of Apoe. Genetics. 2008 May;179(1):693-9
• ID
  MGI:3794624

Genes

Gene	Assay Type
Albq1	resistance/susceptibility

Notes

• Experiment
  Genetic loci affecting albuminuria were mapped in two different F2 intercross populations. The first cross involves 318 (A/J x C57BL/6J)F2 males and the second cross involves 145 (A/J x B6.129P2-Apoe^tm1Unc)F2 males homozygous for the Apoe^tm1Unc mutation. A panel of 98 SNPs and 140 SNPs were used, respectively, for linkage analysis in the first and second cross. Parental strain A/J is susceptible to albuminuria whereas parental strains C57BL/6J and B6.129P2-Apoe^tm1Unc are resistant. Male F2 animals were phenotyped at 8- to 10-weeks of age. Female F2 animals did not display the albuminuria phenotype.
  
  A significant QTL mapped to 70 cM on mouse Chromosome 2 in the (A/J x C57BL/6J)F2 cross with LOD=3.5. This locus is named Albq1 (albuminuria QTL 1). The 95% confidence interval spans 28 cM to 88 cM and A/J-derived alleles confer susceptibility to albuminuria at Albq1 with a recessive mode of inheritance. The Albq1 confidence interval was narrowed to a 51 Mb region between 137 Mb (78 cM) and 178 Mb (91.8 cM) containing 343 genes based on rat/human concordance and interval-specific haplotype mapping. Albq1 appears concordant with a rat QTL for urinary albumin excretion and urinary protein excretion (Rf3, renal failure 3) on rat Chromosome 3 and a human QTL for urinary albumin-to-creatinine ratio on human Chromosome 20p13. A previously identified mouse QTL at 83 cM named Ua1 (urinary albuminuria 1) colocalizes with Albq1.
  
  A suggestive QTL mapped to 5 cM on mouse Chromosome 9 in the (A/J x C57BL/6J)F2 cross with LOD=2. This locus was designated Albq2 (albuminuria QTL 2) because it also shows concordance with a rat QTL for urinary albumin excretion and urinary protein excretion on rat Chromosome 8. Heterozygosity for A/J and C57BL/6J alleles at Albq2 confers albuminuria susceptibility. The 95% confidence interval spans 5 cM to 25 cM.
  
  Albq3 (albuminuria QTL 3) mapped to 24 cM on mouse Chromosome 19 with a suggestive LOD score of 2.1 in the (A/J x C57BL/6J)F2 cross. The 95% confidence interval spans 12 cMto 27 cM and heterozygosity for A/J and C57BL/6J alleles confer resistance to albuminuria. Albq3 is concordant with a rat QTL named Rf1 (renal failure 1) on rat Chromosome 1. Albq3 is also concordant with a human locus linked to creatinine clearance and end-stage renal disease at 10q23.
  
  In the (A/J x B6.129P2-Apoe^tm1Unc)F2 cross, linkage to albuminuria susceptibility mapped to 54 cM on mouse Chromosome 4 (LOD=3.2). This locus is named Albq4 (albuminuria QTL 4). The 95% confidence interval spans 29 cMto 73 cM and A/J-derived alleles at Albq4 confer dominant albuminuria susceptibility in Apoe^tm1Unc homozygous male F2 animals. This locus shows concordance with a rat QTL for creatinine clearance and kidney mass on rat Chromosome 5.
  
  Suggestive linkage to albuminuria was detected at28 cM on mouse Chromosome 6 in the (A/J x B6.129P2-Apoe^tm1Unc)F2 cross with LOD=2.6. At this locus, A/J-derved alleles confer recessively inherited susceptibility to albuminuria.