Overlapping mouse subcongenic strains successfully separate two linked body fat QTL on distal MMU 2.

Overlapping mouse subcongenic strains successfully separate two linked body fat QTL on distal MMU 2.
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DOI:
10.1186/s12864-014-1191-8
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发表时间:
2015-01-23
期刊:
影响因子:
4.4
通讯作者:
Medrano JF
Medrano JF
中科院分区:
生物学2区
文献类型:
--
作者:
Gularte-Mérida R;Farber CR;Verdugo RA;Islas-Trejo A;Famula TR;Warden CH;Medrano JF

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在许多小鼠杂交中,小鼠2号染色体与生长和体脂表型有关。为了确定小鼠2号染色体上调控生长和体脂的潜在基因,我们开发了5个重叠的亚基因菌株,它们包含C57BL/6JHG/HG背景中的CAST/EIJ供体区域(HG是小鼠10号染色体上500kb的自发缺失)。为了精细定位小鼠2号染色体远端的QTL,对5个亚基因品系的1,712只F2小鼠和来自HG2D方正基因品系的278只F2小鼠进行了表型和分析。在SNP和微卫星标记的组合上对体重和体脂性状进行区间作图(IM)和复合区间作图(CIM),形成高密度基因分型小组。表型分析和总脂肪量的区间定位在小鼠2号染色体远端定位了两个QTL,一个在150-161Mb之间,Fatq2a,第二个在173.3-175.6 Mb之间,Fatq2b。这两个QTL位于不同的同源品系中,纯合CAST/CAST和b6/b6窝产仔的总脂肪差异显著。这两个QTL之前都只被确定为影响身体脂肪的单个QTL,Fatq2。此外,通过一种被称为复制CIM的新方法,Fatq2b被映射到GNAS印迹基因座。亚同源菌株的整合、高密度基因分型和CIM成功地将两个先前连锁的QTL分开了20Mb,其中最强的QTL Fatq2b被精细地定位到围绕GNas印记座位的约2.3Mb的区域区间。本文的在线版本(doi:10.1186/s12864-0141191-8)包含补充材料,授权用户可以使用。
Mouse chromosome 2 is linked to growth and body fat phenotypes in many mouse crosses. With the goal to identify the underlying genes regulating growth and body fat on mouse chromosome 2, we developed five overlapping subcongenic strains that contained CAST/EiJ donor regions in a C57BL/6Jhg/hg background (hg is a spontaneous deletion of 500 Kb on mouse chromosome 10). To fine map QTL on distal mouse chromosome 2 a total of 1,712 F2 mice from the five subcongenic strains, plus 278 F2 mice from the HG2D founder congenic strain were phenotyped and analyzed. Interval mapping (IM) and composite IM (CIM) were performed on body weight and body fat traits on a combination of SNP and microsatellite markers, which generated a high-density genotyping panel. Phenotypic analysis and interval mapping of total fat mass identified two QTL on distal mouse chromosome 2. One QTL between 150 and 161 Mb, Fatq2a, and the second between 173.3 and 175.6 Mb, Fatq2b. The two QTL reside in different congenic strains with significant total fat differences between homozygous cast/cast and b6/b6 littermates. Both of these QTL were previously identified only as a single QTL affecting body fat, Fatq2. Furthermore, through a novel approach referred here as replicated CIM, Fatq2b was mapped to the Gnas imprinted locus. The integration of subcongenic strains, high-density genotyping, and CIM succesfully partitioned two previously linked QTL 20 Mb apart, and the strongest QTL, Fatq2b, was fine mapped to a ~2.3 Mb region interval encompassing the Gnas imprinted locus. The online version of this article (doi:10.1186/s12864-014-1191-8) contains supplementary material, which is available to authorized users.
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