Reed Danielle R, McDaniel Amanda H, Li Xia, Tordoff Michael G, Bachmanov Alexander A
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, Pennsylvania 19104, USA.
Mamm Genome. 2006 Nov;17(11):1065-77. doi: 10.1007/s00335-006-0054-2. Epub 2006 Nov 10.
To understand how genotype influences fat patterning and obesity, we conducted an autosomal genome scan using male and female F(2) hybrids between the C57BL/6ByJ and 129P3/J parental mouse strains. Mice were studied in middle-adulthood and were fed a low-energy, low-fat diet during their lifetime. We measured the weight of the retroperitoneal adipose depot (near the kidney) and the gonadal adipose depot (near the epididymis in males and ovaries in females). An important feature of the analysis was the comparison of linkage results for absolute adipose depot weight and depot weight adjusted for body size, i.e., relative weight. We detected 67 suggestive linkages for six phenotypes, which fell into one of three categories: those specific to absolute but not relative depot weight (Chr 5, 11, and 14), those specific to relative but not absolute depot weight (Chr 9, 15, and 16), and those involving both (Chr 2 and 7). Some quantitative trait loci (QTLs) affected one adipose depot more than another: Retroperitoneal depot weight was linked to Chr 8, 11, 12, and 17, but the linkage effects for the gonadal depot were stronger for Chr 5, 7, and 9. Several linkages were specific to sex; for instance, the absolute weight of gonadal fat was linked to Chromosome 7 in male (LOD = 3.4) but not female mice (LOD = 0.2). Refining obesity as a phenotype may uncover clues about gene function that will assist in positional cloning efforts.
为了解基因型如何影响脂肪分布和肥胖,我们利用C57BL/6ByJ和129P3/J亲本小鼠品系之间的雄性和雌性F(2)杂种进行了常染色体基因组扫描。对处于中年期的小鼠进行研究,并在其一生中给予低能量、低脂肪饮食。我们测量了腹膜后脂肪库(靠近肾脏)和性腺脂肪库(雄性靠近附睾,雌性靠近卵巢)的重量。该分析的一个重要特征是比较绝对脂肪库重量和根据体型调整后的脂肪库重量(即相对重量)的连锁结果。我们检测到了67个针对六种表型的提示性连锁,这些连锁可分为三类:仅针对绝对而非相对脂肪库重量的连锁(第5、11和14号染色体)、仅针对相对而非绝对脂肪库重量的连锁(第9、15和16号染色体)以及涉及两者的连锁(第2和7号染色体)。一些数量性状基因座(QTL)对一个脂肪库的影响大于另一个脂肪库:腹膜后脂肪库重量与第8、11、12和17号染色体相关,但性腺脂肪库在第5、7和9号染色体上的连锁效应更强。有几个连锁是性别特异性的;例如,性腺脂肪的绝对重量在雄性小鼠中与第7号染色体相关(LOD = 3.4),而在雌性小鼠中则不相关(LOD = 0.2)。将肥胖细化为一种表型可能会揭示有关基因功能的线索,这将有助于定位克隆工作。