Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Physiol Genomics. 2010 Mar 3;41(1):102-8. doi: 10.1152/physiolgenomics.00178.2009. Epub 2010 Jan 12.
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.
杂合 stock (HS) 动物提供了在相对短的时间内以高分辨率（<5 兆碱基（Mb））映射数量性状基因座的能力。在当前的研究中，我们假设 HS 大鼠群体将有助于精细映射先前与葡萄糖调节有关的大鼠染色体 1 上的一个区域。我们对 515 只 HS 大鼠进行了葡萄糖耐量试验，并使用 69 个微卫星标记对这些动物进行了基因型分析，这些标记平均间隔<1 Mb，位于大鼠染色体 1 的 67 Mb 区域。使用基于隐马尔可夫模型重建的推断单倍型的回归模型和混合模型分析，我们考虑了 HS 的复杂家族结构，在该区域内确定了一个明显的峰值。使用位置引导，我们确定该基因座最可能的位置在 205.04 到 207.48 Mb 之间。这项工作证明了 HS 大鼠在精细映射复杂性状方面的实用性，并强调了在使用高度重组群体时考虑家族结构的重要性。
