Jones H B
Department of Genetics, University of Cambridge, United Kingdom.
Genomics. 1997 Aug 1;43(3):258-66. doi: 10.1006/geno.1997.4803.
Radiation hybrid mapping has become an established tool for building physical maps. It represents a powerful way of constructing YAC contigs and high-resolution maps for positional cloning experiments. Ideally, radiation hybrids should not only provide support for the true order of the markers, but also accurate estimates of the physical distances between them. Statistical analysis of radiation hybrids has proved difficult because of the number of parameters (representing the fragment retention probabilities) that must be estimated, and simplifying assumptions are needed to analyze large numbers of markers simultaneously. The ramifications of these assumptions for the calculation of physical distances are investigated. A simple two-locus model is presented to demonstrate that variation in marker retention can lead to distortions in the estimates of distance. Multilocus simulations show that, when marker retention is constant across the chromosome, good estimates of physical distance can be derived using simple models of retention. However, further simulations exploring variable retention schemes demonstrate that significant errors in the estimates of map distances can occur. Ways of minimizing these distortions are discussed.
辐射杂种图谱构建已成为构建物理图谱的一种成熟工具。它是为定位克隆实验构建酵母人工染色体（YAC）重叠群和高分辨率图谱的一种强大方法。理想情况下，辐射杂种不仅应支持标记的真实顺序，还应能准确估计它们之间的物理距离。由于必须估计的参数数量（代表片段保留概率），对辐射杂种进行统计分析已被证明很困难，因此需要简化假设以便同时分析大量标记。本文研究了这些假设对物理距离计算的影响。提出了一个简单的双位点模型来证明标记保留的变化会导致距离估计的偏差。多位点模拟表明，当整个染色体上的标记保留率恒定时，使用简单的保留模型可以得出较好的物理距离估计值。然而，进一步探索可变保留方案的模拟表明，图谱距离估计中可能会出现重大误差。本文还讨论了将这些偏差降至最低的方法。
