Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content
Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content
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DOI：
10.1007/s003350010002
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发表时间：
2000-01-01
期刊：
影响因子：
2.5
通讯作者：
Keightley, PD
中科院分区：
文献类型：
--
作者：
Horvat, S;Bünger, L;Keightley, PD
对长期选择实验建立的多基因肥胖小鼠模型进行了全基因组QTL分析。亲本系是经过53个世代不同选育的高脂(肥、F系)或低脂(瘦、L系)的亲本，在14周龄时，脂肪百分比相差5倍。对436只Pin FZ小鼠进行了QTL分析，其中71个标记分布在基因组上。Fob1(F系肥胖QTL 1)、Fob2(Fob2)、Fob3(Fob3)和Fob4(Fob4)分别位于第2、12、15和X染色体上。这些QTL没有一个定位到已知的单基因肥胖突变区域(Lep(Ob)，Lepr(Db)，Cpd(FAT)：A(Y)，Tub)，尽管它们映射到先前描述的肥胖QTL和候选基因的区域。Fob1、Fob3、Fob4为加性效应，FobZ为显性效应。FOB2也显示出显著的女性专有效应。Fob1、FobZ、Fob3和Fob4分别解释了F1Fat%表型变异的4.9%、19.5%、14.3%和7.3%。本研究确定了四个基因座对差异选择的反应，并控制了F系和L系之间肥胖差异的很大比例。
A genome-wide quantitative trait locus (QTL) analysis was performed in a polygenic obesity mouse model resulting from a long-term selection experiment. The parental lines were outbred lines divergently selected for 53 generations for high-fat (fat, F line) or low-fat (lean, L line) percentage (fat%) that differed fivefold in fat% at 14 weeks of age. Pin Fz population of 436 mice was used for the QTL analysis with 71 markers distributed across the genome. The analysis revealed significant QTLs Fob1 (for F-line obesity QTL 1), Fob2, Fob3, and Fob4 on Chromosomes (Chrs) 2, 12, 15, and X, respectively. None of these QTLs map to regions of known single gene obesity mutations (Lep(ob), Lepr(db), Cpd(fat): A(y), tub), though they map to regions of previously described obesity QTLs and candidate genes. The effects of Fob1, Fob3, Fob4 were additive, and that of FobZ was dominant. Fob2 also showed a significant female-specific effect. Fob1, FobZ, Fob3, and Fob4 explained 4.9%, 19.5%, 14.3%, and 7.3% of the F, phenotypic variance for fat%, respectively. This study identified four loci that contributed to the response to divergent selection and control a significant proportion of the difference in obesity between the F and L lines.