Mohg1^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Mohg1^CAST/EiJ
• Name: modifier of hg 1; CAST/EiJ
• MGI ID: MGI:3607567
• QTL: Mohg1 Location: Chr2:76678758-103095823 bp Genetic Position: Chr2, cM position of peak correlated region/allele: 45.25 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased body mass index compared to C57BL/6J. (J:111441)
• Inheritance: Recessive

Notes

The effect of Mohg1 is observed on a C57BL/6J-Sosc2^hg genetic background.

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

J:102238

Modifiers of the Socs2^hg high growth mutation were mapped using F2 animals from a cross between C57BL/6J-Socs2^hg and CAST/EiJ. Parental strain C57BL/6J-Socs2^hg exhibits significantly increased growth trajectory after 3 weeks of age compared to CAST/EiJ. F2 animals either homozygous for Socs2^hg or the wild type allele were phenotyped from 2 - 9 weeks of age and 83 polymorphic markers were used for the genome scan.

A growth QTL mapped to mouse Chromosome 2 between D2Mit93 (46 cM) and D2Mit389 (50.3 cM). This locus interacts with the Socs2^hg mutation and is named Mohg1 (modifier of hg 1). C57BL/6J-derived alleles at Mohg1 confer increased growth trajectory in F2 mice homozygous for Socs2^hg with a dominant effect. There is evidence of multiple QTL on chromosome 2. Mohg1 maps near previously identified weight gain QTL Wg1 (31 cM) and Wg2 (61 cM).

Two growth QTL named Mohg2 (modifier of hg 2) and Mohg3 (modifier of hg 3) mapped to 3 cM and 37 cM on mouse Chromosome X, respectively. DXMit54 is the closest marker to Mohg2 and DXMit18 is the closest marker to Mohg3. Heterozygosity for CAST/EiJ- and C57BL/6J-derived alleles at Mohg2 confer increased growth trajectory in F2 animals homozygous for Socs2^hg with an additive effect. Heterozygosity at this locus also increases growth trajectory in wild type F2 animals. C57BL/6J-derived alleles at Mohg3 confer increased growth trajectory in F2 animals homozygous for Socs2^hg with a dominant effect.

J:111441

Previously identified modifiers of the Socs2^hg high growth mutation were analyzed using congenic strains derived from C57BL/6J-Socs2^hg and CAST/EiJ. Parental strain C57BL/6J-Socs2^hg exhibits significantly increased growth trajectory after 3 weeks of age compared to CAST/EiJ.

Overlapping congenic lines spanning 5 regions of chromosome 2 were established. At least one QTL was identified in each region. Mohg1 (modifier of hg 1) at proximal chromosome 2 was confirmed in this study. Mohg1 spans approximately 0 Mb - 40 Mb and is associated with decreased body mass index. A body weight QTL, Wg1 (31 cM; 52 Mb), maps near Mohg1. A novel QTL designated Mohg4 (modifier of hg 4) maps to an interval from 40 Mb - 70 Mb and is associated with body weight, growth rate, and total fat pad weight. Nmi and Mtx2 are potential candidate genes near Mohg4. An interval spanning 70 Mb - 100 Mb designated Mohg5 (modifier of hg 5) is associated with decreased tail length and body length in female animals. Potential candidate genes mapping near Mohg5 include Ubr1 (67.4 cM, 120.6 Mb), Sirpa (formerly Ptpns1, 73.1 cM), and Rbck1 (formerly Ubce7ip3), 130.3 Mb). An interval spanning 100 Mb - 140 Mb designated Mohg6 (modifier of hg 6) shows association with decreased body weight and tail length in males and decreased tail length and adiposity in females. A locus identified on distal chromosome 2 was designated Mohg7 (modifier of hg 7). The Mohg7 interval spans 140 Mb - 180 Mb and is associated with decreased body weight, tail length, adiposity, and body mass index. Potential candidate genes for Mohg6 and Mohg7 include Plcg1 (92 cM, 160.5 Mb) and Mmp9 (96 cM, 164.7 Mb). Previously identified QTL Wg2 (61 cM) overlaps with Mohg5 and Mohg6.

A minor locus on mouse Chromosome 1 was confirmed in this study. Mohg8 (modifier of hg 8) maps to 16 cM (35 Mb) and is associated with body weight, tail length, and body length. Mohg8 also affects tail length in females and mesenteric fat pad in males. The QTL interval spans 4 Mb - 70.6 Mb. Potential candidate genes in this interval are Stat1 (25.9 cM) and Stat4 (25.9 cM).

A locus designated Mohg9 (modifier of hg 9) on mouse Chromosome 8 is associated with adiposity. Mohg9 maps to 45 cM (98 Mb) and the QTL interval spans 70.2 Mb - 104.1 Mb. CAST/EiJ-derived alleles at Mohg9 confer decreased body fat, with the most significant effect seen in females (25% body fat reduction). Previously identified QTL Wg3 (45 cM) maps near Mohg9.

Carfhg2 (10 cM, 30 Mb) was confirmed on mouse Chromosome 9. The Carfhg2 interval spans 9.1 Mb - 84.2 Mb. CAST/EiJ-derived alleles at Carfhg2 confer increased body fat. Feml2 (20 cM, 48 Mb) also maps to this interval and was confirmed in this study. CAST/EiJ-derived alleles at Feml2 confer decreased body length.

On mouse Chromosome 11, an interval at 46 cM (80 Mb) - 50 cM (90 Mb) is associated with sex-specific growth and obesity traits. This locus is thought to correspond to Carp2. CAST/EiJ-derived alleles at Carp2 confer increased body weight, growth rate, and body length in males. In females, CAST/EiJ-derived alleles atCarp2 confer increased fat pad weight and increased carcass fat percentage. The maximum Carp2 QTL interval spans 61.9 Mb - 114.3 Mb. Wg4 (46 cM) and Cara2 (50 cM) are previously identified QTLs mapping near Carp2.

Feml3 (48 cM, 76 Mb), Carp3 (46 cM), andCara3 (48 cM) were all detected on mouse Chromosome 17 within an interval spanning 14.8 Mb - 77.3 Mb. CAST/EiJ-derived alleles at Feml3 confer decreased femur length, decreased body length, increased body weight at 2 weeks of age, and decreased body weight at 9 weeks of age. CAST/EiJ-derived alleles at Carp3 confer decreased carcass protein percentage in female animals, and CAST/EiJ-derived alleles at Cara3 confer decreased carcass ash. A potential candidate gene is Sstr5 (13 cM).

References

• Original: J:102238 Wu R, et al., Functional mapping of quantitative trait loci that interact with the hg mutation to regulate growth trajectories in mice. Genetics. 2005 Sep;171(1):239-49
• All: 2 reference(s)