NON-INVASIVE PRENATAL DIAGNOSIS OF FETAL GENETIC CONDITION USING CELLULAR DNA AND CELL FREE DNA

摘要

Disclosed are methods for determining at least one sequence of interest of a fetus of a pregnant mother. In various embodiments, the method can determine one or more sequences of interest in a test sample that comprises a mixture of maternal cellular DNA and mother-and-fetus cfDNA. In some embodiments, methods are provided for determining whether the fetus has a genetic disease. In some embodiments, methods are provided for determining whether the fetus is homozygous in a disease causing allele when the mother is heterozygous of the same allele. In some embodiments, methods are provided for determining whether the fetus has a copy number variation (CNV) or a non-CNV genetic sequence anomaly.

主权项

1. A method for determining at least one sequence of interest of a fetus of a pregnant mother, the method comprising:
(a) obtaining mother-only cellular DNA of the pregnant mother, wherein the mother-only cellular DNA has a sequence that maps to the at least one sequence of interest; (b) obtaining mother-and-fetus mixed cfDNA from the pregnant mother, wherein the mother-and-fetus mixed cfDNA has a sequence that maps to the at least one sequence of interest; (c) applying an indicator to at least one of the mother-only cellular DNA and the cfDNA, wherein the indicator identifies a source of DNA as being from the mother-only cellular DNA or the cfDNA; (d) combining the mother-only cellular DNA and the cfDNA to provide a sample of combined cellular DNA and cfDNA; (e) sequencing said sample of combined cellular and cfDNA to provide a plurality of sequence tags; and (f) analyzing the plurality of sequence tags to determine the presence and/or abundance of the at least one sequence of interest in the fetus's DNA, wherein at least a portion of the plurality of sequence tags map to the at least one sequence of interest.