Segmental polymorphisms in the human genome

描述(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。随着基于高分辨率阵列的基因组扫描技术被应用于检测超出细胞遗传学技术分辨率的微小的染色体异常，区分检测到的异常是因果的还是普通人群中存在的正常变异变得重要。最近的研究表明，大片段染色体的拷贝数变异在普通人群中相当常见。在这项研究中，我们建议开发和应用完全覆盖基因组的FOSMID克隆阵列来分析大量不同种族来源的正常个体的基因组，以获得没有明显表型的基因组片段的全球变异性。这将提供具有普遍参考价值的人口基线数据，为使用基于高分辨率阵列的技术在各种人类综合征中检测到的新的微妙染色体异常建立表型-基因相关性的未来努力。这些数据将为基因组结构和疾病易感性的研究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.