Bailey Jeffrey A, Gu Zhiping, Clark Royden A, Reinert Knut, Samonte Rhea V, Schwartz Stuart, Adams Mark D, Myers Eugene W, Li Peter W, Eichler Evan E
Department of Genetics, Center for Computational Genomics, and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Science. 2002 Aug 9;297(5583):1003-7. doi: 10.1126/science.1072047.
Primate-specific segmental duplications are considered important in human disease and evolution. The inability to distinguish between allelic and duplication sequence overlap has hampered their characterization as well as assembly and annotation of our genome. We developed a method whereby each public sequence is analyzed at the clone level for overrepresentation within a whole-genome shotgun sequence. This test has the ability to detect duplications larger than 15 kilobases irrespective of copy number, location, or high sequence similarity. We mapped 169 large regions flanked by highly similar duplications. Twenty-four of these hot spots of genomic instability have been associated with genetic disease. Our analysis indicates a highly nonrandom chromosomal and genic distribution of recent segmental duplications, with a likely role in expanding protein diversity.
灵长类特有的片段重复被认为在人类疾病和进化中很重要。无法区分等位基因和重复序列重叠阻碍了它们的特征描述以及我们基因组的组装和注释。我们开发了一种方法，通过该方法在克隆水平分析每个公共序列在全基因组鸟枪法测序中的过度代表性。该测试能够检测大于15千碱基的重复，而不考虑拷贝数、位置或高序列相似性。我们绘制了169个由高度相似的重复序列侧翼的大区域。这些基因组不稳定热点中的24个与遗传疾病有关。我们的分析表明，近期片段重复具有高度非随机的染色体和基因分布，可能在扩展蛋白质多样性方面发挥作用。
