COATE-seq was specifically developed for the concurrent detection of chromosomal and single-gene disorders by the analyses of fetal cell-free DNA present in maternal blood. Followed by multidimensional genomic analyses of sequencing read-depth, allelic fraction, and genetic linkage, the fetal genome is genetically deconvoluted from maternal background, allowing for highly sensitive and accurate detection of various genetic disorders. This encompasses genetic aberrations ranging from single nucleotide variants to a whole chromosome copy number change, significantly improving the detection yield of severe genetic disorders.