Kwok P Y, Deng Q, Zakeri H, Taylor S L, Nickerson D A
Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Genomics. 1996 Jan 1;31(1):123-6. doi: 10.1006/geno.1996.0019.
Physical maps of the human genome are being constructed by many groups using a mapping strategy that relies on the development of sequence-tagged sites (STSs). Thousands of physically mapped STSs, representing hundreds of kilobases (kb) of unique human DNA sequence, have been generated by these efforts. Since sequence variations are found every 1-2 kb in the genome, it is possible to extract additional information from mapped STSs by scanning them for variations. By screening 154 of the STSs published by the Whitehead Institute/MIT Genome Center, we have identified 47 new DNA sequence polymorphisms among the 37.2 kb of unique DNA sequence contained in these STSs. Using a sequence-based approach to estimate allele frequencies for these variations, 29 of the substitution polymorphisms (1 in 1.3 kb) were found to have heterozygosities exceeding 32%. Our study shows that the information content of STS-based genome maps can be increased with minimal additional effort by scanning for DNA polymorphisms, and that ambiguities and errors in the initial STS sequence can be resolved and corrected in the process.
许多研究小组正在采用一种依赖于序列标签位点（STS）开发的定位策略来构建人类基因组的物理图谱。通过这些努力，已经产生了数千个物理定位的STS，它们代表了数百千碱基（kb）的独特人类DNA序列。由于在基因组中每1 - 2 kb就会发现序列变异，因此通过扫描定位的STS以寻找变异，有可能从中提取额外信息。通过筛选怀特黑德研究所/麻省理工学院基因组中心公布的154个STS，我们在这些STS所含的37.2 kb独特DNA序列中鉴定出了47个新的DNA序列多态性。使用基于序列的方法来估计这些变异的等位基因频率，发现29个替代多态性（每1.3 kb中有1个）的杂合度超过32%。我们的研究表明，通过扫描DNA多态性，只需付出最小的额外努力就能增加基于STS的基因组图谱的信息含量，并且在此过程中可以解决和纠正初始STS序列中的模糊性和错误。
