Taylor B A, Wnek C, Schroeder D, Phillips S J
The Jackson Laboratory, Bar Harbor, Maine 04609-1500, USA.
Mamm Genome. 2001 Feb;12(2):95-103. doi: 10.1007/s003350010254.
The inheritance of adiposity levels has been investigated in an intercross of the obese, diabetes-prone NZO and the small, lean SM mouse strains. Adiposity index (AI) was defined as the sum of four fat pad weights divided by body weight. DNA pools from fat and lean mice were analyzed with microsatellite variants to screen the genome for quantitative trait loci (QTLs) affecting AI. Ten significant QTLs affecting AI were identified on Chromosome (Chr) 1 (three loci), Chr 2, Chr 5 (two loci), Chr 6 (two loci), Chr 7, and Chr 17. Most of the QTLs appear to be novel. Several QTLs differentially affect specific fat depots. Thus, Chr 2 and Chr 7 QTLs affect gonadal more than inguinal fat, while the converse is true for the Chr 17 QTL. Gender influences the expression of several of the QTLs. For example, effects of the proximal Chr 1 QTL (Obq7) on AI appears to be primarily in males. The proximal AI QTL on Chr 6 (Obq13) maps near the neuropeptide Y (Npy) locus. Sequence analysis of the Npy gene revealed a 1-nucleotide deletion within a highly conserved portion of the 3' untranslated region in strain NZO. However, the deletion is polymorphic among mouse strains. Furthermore, lack of association between this same variant and AI in previously analyzed crosses raises doubt that it is the basis of Obq13. The present cross is the fourth in a series of intercrosses among 10 inbred strains arranged such that each strain is crossed with each adjacent strain within a circle. This design affords multiple opportunities to analyze each segregating QTL.
在肥胖、易患糖尿病的新西兰肥胖小鼠（NZO）和体型小且瘦的SM小鼠品系的杂交后代中，对肥胖水平的遗传情况进行了研究。肥胖指数（AI）定义为四个脂肪垫重量之和除以体重。用微卫星变体分析肥胖和瘦小鼠的DNA池，以筛选基因组中影响AI的数量性状基因座（QTL）。在第1号染色体（Chr）（三个基因座）、Chr 2、Chr 5（两个基因座）、Chr 6（两个基因座）、Chr 7和Chr 17上鉴定出10个影响AI的显著QTL。大多数QTL似乎是新发现的。几个QTL对特定脂肪库有不同影响。因此，Chr 2和Chr 7的QTL对性腺脂肪的影响大于腹股沟脂肪，而Chr 17的QTL则相反。性别影响几个QTL的表达。例如，近端Chr 1 QTL（Obq7）对AI的影响似乎主要在雄性中。Chr 6上的近端AI QTL（Obq13）定位在神经肽Y（Npy）基因座附近。Npy基因的序列分析显示，在NZO品系3'非翻译区的高度保守部分内有一个1核苷酸缺失。然而，该缺失在小鼠品系中是多态性的。此外，在先前分析的杂交中，这个相同变体与AI之间缺乏关联，这让人怀疑它是否是Obq13的基础。本次杂交是10个近交系之间一系列杂交中的第四次，这些杂交系按如下方式排列：每个品系与圆圈内的每个相邻品系杂交。这种设计为分析每个分离的QTL提供了多次机会。
