bookmark FSDA / Fragment-Size Distribution Analysis An alternative framework for identifying sub-chromosomal copy number variants in a fetal genome. This framework relies on the size-distribution of fragments in a sample, as fetal-origin fragments tend to be smaller than maternal-origin. By analyzing the local distribution of the cell-free DNA fragment sizes in each region our method allows for the identification of sub-megabase CNVs, even in the absence of SNP positions. To evaluate the accuracy of our method, we used a plasma sample with the fetal fraction of 13%, down-sampled it to samples with coverage of 10X to 40X and simulated samples with CNVs based on it. Our method had a perfect accuracy (both specificity and sensitivity) for detecting 5 Mbp CNVs, and after reducing the fetal fraction (to 11%, 9% and 7%), it could correctly identify 98.82% to 100% of the 5 megabase CNVs and had a true negative rate of 95.29% to 99.76%.