Inference of haplotypes from PCR-amplified samples of diploid populations.
Inference of haplotypes from PCR-amplified samples of diploid populations.
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DOI：
10.1093/oxfordjournals.molbev.a040591
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发表时间：
1990-03
影响因子：
10.7
通讯作者：
A. Clark
中科院分区：
文献类型：
--
作者：
A. Clark
当一个基因的两个直系同源拷贝的序列中存在多个错配位点时，对二倍体个体的基因组DNA进行直接测序会导致测序凝胶上的歧义。虽然如果不借助其他实验方法（例如以传统方式克隆），就无法从单个样本中解决这些歧义，但群体样本可能有助于推断单倍型。对于样本中扩增序列纯合的每个个体，等位基因序列的识别不存在歧义。其他等位基因的序列可以通过“减去”每个已知位点的测序阶梯后剩余的序列来推断。这里介绍了从此类数据中提取等位基因序列的算法的详细信息，以及影响该方法成功可能性的一些群体遗传因素。该算法还适用于推断紧密连锁的限制性位点多态性的单倍型频率的问题。
Direct sequencing of genomic DNA from diploid individuals leads to ambiguities on sequencing gels whenever there is more than one mismatching site in the sequences of the two orthologous copies of a gene. While these ambiguities cannot be resolved from a single sample without resorting to other experimental methods (such as cloning in the traditional way), population samples may be useful for inferring haplotypes. For each individual in the sample that is homozygous for the amplified sequence, there are no ambiguities in the identification of the allele's sequence. The sequences of other alleles can be inferred by taking the remaining sequence after "subtracting off" the sequencing ladder of each known site. Details of the algorithm for extracting allelic sequences from such data are presented here, along with some population-genetic considerations that influence the likelihood for success of the method. The algorithm also applies to the problem of inferring haplotype frequencies of closely linked restriction-site polymorphisms.