Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice
Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice
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DOI：
10.1007/s003350010218
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发表时间：
2001-01-01
期刊：
影响因子：
2.5
通讯作者：
King-Ellison, KJ
中科院分区：
文献类型：
--
作者：
Cheverud, JM;Vaughn, TT;King-Ellison, KJ
人类肥胖变异的遗传基础被认为是由于许多影响相对较小的基因及其相互作用。LG/J与SM/J小鼠近交系的互交为研究多基因肥胖提供了一个良好的模型系统。我们以前在这个杂交中定位了大量影响成年体重的数量性状基因座（QTL）。我们映射的身体组成特征，肥胖，骨骼大小，在一个重复的F-2交叉相同的两个菌株包含510个人。利用区间作图法定位了8个影响肥胖的QTL（Adip1 - 8）。其中两个肥胖基因座（Adip 4和Adip 6）沿着7个额外的尾长QTL（Skl 1 - 7）也影响尾长。另外4个QTL（Wt1 - 4）影响成鱼体重，但不影响鱼体组成。这些QTL具有相对较小的效应，通常约为0.2 - 0.4标准差单位，并占单个性状方差的3%-10%。所有QTL均与其它QTL互作。这些相互作用中的大多数是由于加性-加性上位性，这可以抵消在我们的人口中的单个位点的明显效果。Adip8与所有其他肥胖QTL相互作用，似乎在该杂交中影响肥胖的遗传系统中发挥核心作用。只有两个肥胖QTL。Adip4和Adip6也影响尾巴长度，这表明肥胖和骨骼大小的变异在很大程度上是独立的遗传控制。与本文发现的位置相同的体型和肥胖QTL通常在其他小鼠品系的作图实验中发现。
The genetic basis of variation in obesity in human populations is thought to be owing to many genes of relatively small effect and their interactions. The LG/J by SM/J intercross of mouse inbred strains provides an excellent model system in which to investigate multigenic obesity. We previously mapped a large number of quantitative trait loci (QTLs) affecting adult body weight in this cross. We map body composition traits, adiposity, and skeletal size, in a replicate F-2 intercross of the same two strains containing 510 individuals. Using interval-mapping methods, we located eight QTLs affecting adiposity (Adip1-8). Two of these adiposity loci also affected tail length (Adip4 and Adip6) along with seven additional tail length QTLs (Skl1-7). A further four QTLs (Wt1-4) affect adult weight but not body composition. These QTLs have relatively small effects, typically about 0.2-0.4 standard deviation units, and account for between 3% and 10% of the variance in individual characters. All QTLs participated in epistatic interactions with other QTLs. Most of these interactions were due to additive-by-additive epistasis, which can nullify the apparent effects of single loci in our population. Adip8 interacts with all the other adiposity QTLs and seems to play a central role in the genetic system affecting obesity in this cross. Only two adiposity QTLs. Adip4 and Adip6 also affect tail length, indicating largely separate genetic control of variation in adiposity and skeletal size. Body size and obesity QTLs in the same locations as those discovered here are commonly found in mapping experiments with other mouse strains.