通过熵理论使用核心家系进行精细定位(英文)

Fine-Scale Mapping Human Complex Traits in Nuclear Families Via Entropy

针对精细定位人类复杂性状基因位点,我们拓展了基于熵的连锁不平衡指数到使用病例-父母和无关的对照-父母设计的家系研究.这个指数比较杂合子父母传递给受累子代和非受累子代基因的熵和条件熵.在单一群体和混合群体两种情形下,我们通过模拟调查了该指数的性质.结果表明在不同遗传模型下利用该指数定位的概率随着样本容量的增大而增大.当样本容量超过200,显性模型和加性模型的概率在90%以上.当样本容量超过300,隐性模型和乘积模型的概率在80%以上.当存在群体混杂时,该指数仍然适用于精细定位.

We present an extension of the entropy-based linkage disequilibrium(LD) measure for fine-scale mapping of human complex traits using family-based study incorporating case-parents and unrelated control-parents trios.This measure here compared the entropy and the conditional entropy of transmitting alleles from the heterozygous parents to the affected offspring and from the heterozygous parents to the unaffected offspring.We investigate the mapping performance in simulation scenarios of a single disease-susceptibility locus(DSL) linked to a single marker in a homogeneous population and in an admixture population.Our results show that the probabilities for fine mapping increase when the sample sizes increase for different genetic models.The probabilities are above 90%for the dominant and additive models when the sample sizes is larger than 200,and the probabilities are above 80%for the recessive and multiplicative models when the sample sizes is larger than 300.The results also show that the measure here is also appropriate for fine-scale mapping if there is population admixture.