Noninvasive prenatal molecular karyotyping from maternal plasma

A computer product comprising a non-transitory computer readable medium storing a plurality of instructions that when executed control a computer system to identify microamplifications or microdeletions in a genome of a fetus by analyzing a biological sample obtained from a female subject pregnant with the fetus, the biological sample including cell-free DNA from the fetus and from the female subject, the method comprising:

• receiving one or more sequence tags for each of a plurality of DNA fragments in a biological sample;
• determining genomic positions for the sequence tags;
• for each of a plurality of genomic regions:
• determining a respective amount of DNA fragments within the genomic region from sequence tags having genomic positions within the genomic region;
• normalizing the respective amount to obtain a respective density;
• and
• comparing the respective density to a reference density to identify whether the respective density is statistically different from the reference density;
• determining whether any of the genomic regions identified to have a respective density statistically different from the reference density is consecutive with another genomic region identified to have a respective density statistically different from the reference density;
• when at least N first genomic regions identified to have respective densities statistically higher than the reference density are consecutive, identifying the first consecutive genomic regions as a microamplification, N being an integer equal to or greater than two;
• when at least N second genomic regions identified to have respective densities statistically lower than the reference densities are consecutive, identifying the second consecutive genomic regions as a microdeletion.