Experiment
Previously identified modifiers of the Socs2hg high growth mutation were analyzed using congenic strains derived from C57BL/6J-Socs2hg and CAST/EiJ. Parental strain C57BL/6J-Socs2hg 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).
Analysis Tools