Detection of fetal chromosome partial aneuploidy and copy number variation

摘要

Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. This includes CNV-related syndromes in chromosomal subregions, where bins from unaffected training samples used as controls have coverage similar to that of the regions examined for CNV. In some embodiments, a method is provided for determining fetal CNV using a maternal sample containing maternal and fetal cell-free DNA. Some embodiments disclosed herein provide methods to improve the sensitivity and / or specificity of sequence data analysis by removing the intra-sample GC content bias. In some embodiments, removal of the intra-sample GC content bias is based on sequence data corrected for the systematic variation common across unaffected training samples. In some embodiments, the bias associated with the syndrome in the sample data is also removed to increase the signal to noise ratio. A system for CNV evaluation of a sequence of interest is also disclosed.