NONINVASIVE PRENATAL MOLECULAR KARYOTYPING FROM MATERNAL PLASMA

摘要

Disclosed herein are methods, systems, and apparatus for detecting microamplifications or microdeletions in the genome of a fetus. In some embodiments, the method comprises receiving sequence tags for each of a plurality of DNA fragments in a biological sample; determining genomic positions for the sequence tags; determining whether the density of DNA in each of a plurality of genomic regions is aberrantly high or low; identifying as a microamplification a set of consecutive genomic regions having aberrantly high density; and identifying as a microdeletion a set of consecutive genomic regions having aberrantly low density. The biological sample may be a blood sample obtained noninvasively from a female subject pregnant with the fetus.

主权项

1. A method of identifying 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 the biological sample; determining genomic positions for the sequence tags; for each of a plurality of genomic regions:
determining, with a computer system, 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; andcomparing 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.