Bw4^DU6
QTL Variant Detail

Summary

• QTL variant: Bw4^DU6
• Name: body weight QTL 4; DU6
• MGI ID: MGI:2158215
• QTL: Bw4 Location: unknown Genetic Position: Chr11, cM position of peak correlated region/allele: 50.86 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DU6

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased body weight compared to DUKs. (J:49578)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Bw4 exhibits additive inheritance.

Candidate Genes

J:91835

The correlation between gene expression and dietary interaction was examined in a population of (BALB/cStCrlfC3H/Nctr x VY/WffC3Hf/Nctr-A(vy)/a)F1 animals. A/a and A/A^vy animals were placed on a 70% (calorie restricted) or 100% (non-restricted) diet andliver mRNA levels were assessed for over 18,000 genes using DNA microarrays. Twenty-eight known genes showing statistically significant differential expression between the 70% and 100% calorie diets and A/a and A/A^vy genotypes mapped near known diabesity QTLs. These genes may be considered further for candidate genes.

On mouse Chromosome 11, candidate genes for diabesity QTL Nidd4n (2 cM) are Dbn1 (34 cM- **Note: Location of Dbn1 is 34 cM on mouse Chromosome 13 according to mapping data in the MGI database**) and Dvl2 (36.5 cM). Both Dbn1 and Dvl2 show differential expression on the restricted and unrestricted diets on the A/A^vy background.

Candidate genes for diabesity QTLs Nidd1n (31 cM), Bwtq5 (27.8 cM), Wt10q3 (32 cM), Wt6q3 (36 cM) are Nola2 (28.5 cM, formerly Nhp2), Sept8 (28.75 cM), Skp1a (31 cM), and Mpdu1 (39 cM). Skp1a and Nola2 both show differential expression between restricted and unrestricted diets on the A/A^vy background. Sept8 shows differential expression between A/a and A/A^vy animals on the restricted diet.

Candidate genes for diabesity QTLs Wg4 (46 cM) and Bw4 (55 cM) are Dusp14 (48 cM), Spag7 (42 cM), Derl2 (42 cM, formerly Flana), Sfrs1 (49 cM), and Rara (57.8 cM). Dusp14, Derl2, and Spag7 all show differential expression between A/a and A/A^vy animals on the restricted diet. Sfrs1 shows differential expression between the restricted and unrestricted diets on the A/a background. Rara shows differential expression between the restricted and unrestricted diet on the A/a background as well as between A/a and A/A^vy animals on the restricted diet.

Fasn (72 cM) and Grb2 (75 cM) are candidate genes for diabesity QTL Nidd4 (68 cM). Fasn shows differential expression between restricted and unrestricted diets on the A/A^vy background while Grb2 shows differential expression between A/a and A/A^vy animals on the unrestricted diet.

J:123128

A search for candidate genes was performed using DU6 and DU6i high body weight selection lines and lean unselected lines DUKs and DBA/2. RNA from epididymal fat tissue of 20 males from each line (DU6, DU6i, DUKs and DBA2/J) was pooled for analysis in Affymetrix GeneChips and resulted in the identification of 77 differentially expressed candidate genes. Of these, 14 genes are located in QTLs intervals affecting body weight and abdominal fat weight.

On mouse Chromosome 4, candidate gene Ak2 (61 cM) is upregulated in selected lines while candidate gene Ubxd5 at 65.7 cM (formerly 4930506L07Rik) is downregulated in selected lines. These genes map to the Afw14 QTL interval at 66 cM.

On mouse Chromosome 5, candidate gene Mcm7 is downregulated in selected lines compared to unselected lines. This gene is located near the Afw15 (80 cM) and Bw13 (81 cM) QTL intervals.

On mouse Chromosome 7, candidate genes Ldhc (23.5 cM) and Stard10 exhibit decreased expression in selected versus unselected lines. These genes are located near the Afw9 (23 cM) QTL interval.

On mouse Chromosome 11, candidate gene Prkca (68 cM) is upregulated in selected lines versus unselected lines. Candidate genes Ero1lb (formerly 1300013B24Rik-*note the current location of this gene according to assembly data inthe Mouse Genome Database is chromosome 13) and EST AA178476 map to the Bw4 QTL interval at 55 cM and display increased expression in selected lines compared to unselected lines. Zpbp is down-regulated in selected lines compared tounselected lines and maps to the Afw5 (10 cM) and Bw16 (14 cM) QTL intervals.

On mouse Chromosome 12, candidate gene Serpina3c maps near the Afw10 (21 cM) and Bw9 (17 cM) QTL intervals and is upregulated in selected lines. These genes are upregulated inselected lines compared to unselected lines. Candidate gene Cox8a (*note- the current location of this gene according to data in the Mouse Genome Database is chromosome 19) also maps to the same QTL intervals but is downregulated in selected lines comparedto unselected lines. Candidate gene Igh-1a (58 cM) maps near QTL Afw10 and is upregulated in selected lines compared to unselected lines.

On mouse Chromosome 13, candidate genes Hfe (15 cM) and Hist1h1c (formerly H1f2) map near the Afw18 QTL interval (11cM). These genes are upregulated in selected lines compared to unselected lines.

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

J:49578

F2-intercross pedigree analysis of progeny from crosses between a single male of the outbred mouse line DU6 (selected for high body weight) and a DUKs female (a randomly mated control line) was used to map quantitative trait loci (QTL). A QTL linked with body weight, Bw4, was placed at 42 cM in the vicinity of D11Mit120 on mouse Chromosome 11. A QTL associated with abdominal fat weight, Afw5, was placed at 6 cM. A QTL associated with liver weight, Lwq4, was placed at 50 cM. A QTL linked with speen weight, Swq1, was placed at 52 cM.

References

• Original: J:49578 Brockmann GA, et al., Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth. Genetics. 1998 Sep;150(1):369-81
• All: 1 reference(s)