Segmental polymorphisms in the human genome

描述（由申请人提供）：体质染色体异常在人类发育障碍中很常见。传统的细胞遗传学技术在揭示这种异常方面取得了巨大的成功。由于基于高分辨率阵列的基因组扫描技术正被应用于检测超出细胞遗传学技术分辨率的细微染色体异常，因此区分检测到的异常是因果关系还是只是普通人群中存在的正常变异变得非常重要。最近的研究表明，大染色体片段的拷贝数变异在一般人群中是相当普遍的。在这项研究中，我们建议开发和应用具有完整基因组覆盖的fosmid克隆阵列来分析大量不同种族血统的正常个体的基因组，以获得基因组片段无明显表型变异性的全局视图。这将为未来利用高分辨率阵列技术在各种人类综合征中检测到的新型细微染色体异常建立表型-基因型相关性提供具有一般参考价值的人群基线数据。这些数据将为研究基因组结构和疾病易感性以及基因组进化提供重要的基础。

DESCRIPTION (provided by applicant): Constitutional chromosomal abnormalities are common in human developmental disorders. Conventional cytognetic techniques have been tremendously successful in revealing such abnormalities. As high-resolution array based genome scanning technologies are being applied to detect subtle chromosomal abnormalities that are beyond the resolution of cytogenetics techniques it becomes important to distinguish whether the detected abnormalities are causal or just normal variants that exist in the general population. Recent studies indicated that copy number variations of large chromosomal segments are quite common in the general population. In this study, we propose to develop and apply fosmid clone arrays with complete genome coverage to analyze the genomes of a large number of normal individuals of different ethnic origin to obtain a global view of the variability of genomic segments without obvious phenotypes. This will provide the population baseline data that are of general reference value for future efforts of establishing phenotype- genotype correlation for novel subtle chromosomal abnormalities detected in various human syndromes using high-resolution array based technologies. These data will provide an important foundation for study of genomic structure and disease susceptibilities as well as genome evolution.