Fine-mapping a locus for glucose tolerance using heterogeneous stock rats.
Fine-mapping a locus for glucose tolerance using heterogeneous stock rats.
复制标题
使用异种大鼠精细绘制葡萄糖耐量位点。
DOI：
10.1152/physiolgenomics.00178.2009
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发表时间：
2010
影响因子：
4.6
通讯作者：
Valdar,William
中科院分区：
文献类型：
--
作者：
SolbergWoods,LeahC;Holl,Katie;Tschannen,Michael;Valdar,William
异质原种（HS）动物提供了在相对短的时间段内以高分辨率[<5兆碱基（Mb）]定位数量性状基因座的能力。在目前的研究中，我们假设HS大鼠群体将是有用的精细映射的区域在大鼠1号染色体上，以前已经牵连在葡萄糖调节。我们对515只HS大鼠进行了葡萄糖耐量试验，并用69个微卫星标记对这些动物进行了基因分型，这些标记位于大鼠1号染色体的67 Mb区域，平均间距<1 Mb。使用基于隐马尔可夫模型重建和混合模型分析的推断单倍型的回归建模，其中我们考虑了HS的复杂家族结构，我们在该区域内确定了一个尖锐的峰。使用位置自举法，我们确定该位点最可能的位置是从205.04到207.48 Mb。这项工作证明了HS大鼠精细映射复杂性状的实用性，并强调了在使用高度重组群体时考虑家族结构的重要性。
Heterogeneous stock (HS) animals provide the ability to map quantitative trait loci at high resolution [<5 Megabase (Mb)] in a relatively short time period. In the current study, we hypothesized that the HS rat colony would be useful for fine-mapping a region on rat chromosome 1 that has previously been implicated in glucose regulation. We administered a glucose tolerance test to 515 HS rats and genotyped these animals with 69 microsatellite markers, spaced an average distance of <1 Mb apart, on a 67 Mb region of rat chromosome 1. Using regression modeling of inferred haplotypes based on a hidden Markov model reconstruction and mixed model analysis in which we accounted for the complex family structure of the HS, we identified one sharp peak within this region. Using positional bootstrapping, we determined the most likely location of this locus is from 205.04 to 207.48 Mb. This work demonstrates the utility of HS rats for fine-mapping complex traits and emphasizes the importance of taking into account family structure when using highly recombinant populations.