Linkage analysis in the presence of errors I:: Complex-valued recombination fractions and complex phenotypes
Linkage analysis in the presence of errors I:: Complex-valued recombination fractions and complex phenotypes
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DOI：
10.1086/302797
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发表时间：
2000-03-01
影响因子：
9.8
通讯作者：
Terwilliger, JD
中科院分区：
文献类型：
--
作者：
Göring, HHH;Terwilliger, JD
连锁是一种基因座的基因型相关的现象，而不是一个基因座的表型与另一个基因座的基因型相关。因此，有必要将观察到的性状表型转换为性状基因座基因型，然后可以与标记基因座基因型进行共遗传分析。然而，如果不准确地知道性状的遗传模式，这种转换往往会导致推断的性状基因座基因型的错误，这反过来又会导致减数分裂重组状态的错误分类。因此，在两点分析中，重组分数可能被高估，而在多点分析中，可能会出现对真实性状位点的错误排除。我们提出了一种方法，通过明确允许对性状基因座基因型进行错误分类，增加了多点分析对性状遗传假设模式中错误的鲁棒性。为此，将复合分数的定义扩展到复平面，如θ = θ + θ i; θ是标记基因座和性状基因座的实际（“真实的”）基因型之间的重组分数，（“假想的”）实际和推断的性状基因座基因型之间的重组，“复杂”多点LOD分数被证明是随机等效于传统的两点LOD分数。因此，对通常与两点分析相关联的建模误差的更大鲁棒性可以扩展到多个两点分析和多点分析。复值重组分数的使用也允许随机等价的“基于模型”和“无模型”的方法被扩展到多点分析。
Linkage is a phenomenon that correlates the genotypes of loci, rather than the phenotypes of one locus to the genotypes of another. It is therefore necessary to convert the observed trait phenotypes into trait-locus genotypes, which can then be analyzed for coinheritance with marker-locus genotypes. However, if the mode of inheritance of the trait is not known accurately, this conversion can often result in errors in the inferred trait-locus genotypes, which, in turn, can lead to the misclassification of the recombination status of meioses. As a result, the recombination fraction can be overestimated in two-point analysis, and false exclusions of the true trait locus can occur in multipoint analysis. We propose a method that increases the robustness of multipoint analysis to errors in the mode of inheritance assumptions of the trait, by explicitly allowing for misclassification of trait-locus genotypes. To this end, the definition of the recombination fraction is extended to the complex plane, as theta = theta + epsilon i; theta is the recombination fraction benveen actual ("real") genotypes of marker and trait loci, and epsilon is the probability of apparent but false ("imaginary") recombinations between the actual and inferred trait-locus genotypes, "Complex" multipoint LOD scores are proven to be stochastically equivalent to conventional two-point LOD scores. The greater robustness to modeling errors normally associated with two-poiut analysis can thus be extended to multiple two-point analysis and multipoint analysis. The use of complex-valued recombination fractions also allows the stochastic equivalence of "model-based" and "model-free" methods to be extended to multipoint analysis.