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. ? ?