Marker for prenatal diagnosis and monitoring
AssigneeThe Chinese University of Hong Kong
InventorsYuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Stephen Siu-Chung Chim, Yu-Kwan Tong, Chunming Ding
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Abstract
The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.
Claims25
A method for detecting or monitoring a pregnancy-associated disorder in a woman pregnant with a fetus, comprising the steps of:
- (a) obtaining a blood sample from the woman;
- (b) determining the methylation status of at least a portion of the maspin gene in the blood sample, wherein the portion of the maspin gene from the fetus and the portion from the woman are differentially methylated, thereby distinguishing the maspin gene from the woman and the maspin gene from the fetus in the blood sample;
- (c) determining the level of the fetal maspin gene;
- and
- (d) comparing the level of the fetal maspin gene with a standard control, wherein an increase or decrease from the standard control indicates the presence or progression of a pregnancy-associated disorder.
-8. (canceled)
A method for detecting or monitoring a pregnancy-associated disorder in a woman pregnant with a fetus, comprising the steps of:
- (a) obtaining DNA in a blood sample from the woman;
- (b) treating the DNA from step (a) with bisulfate;
- and
- (c) performing an amplification reaction using the DNA from step (b) and two primers to amplify at least a portion of the maspin gene, wherein the portion of the maspin gene from the fetal DNA and the portion of the maspin gene from the maternal DNA in the blood sample are differentially methylated, and wherein at least one of the two primers binds differentially to the portion of the maspin gene from the fetus;
- and
- (d) comparing the level of the amplified portion of the maspin gene from step (c) with a standard control, wherein an increase or decrease from the standard control indicates the presence or progression of a pregnancy-associated disorder.
13-24. (canceled)
A method for detecting the maspin gene from a fetus in the blood of a pregnant woman, comprising the steps of:
- (a) obtaining a blood sample from the woman;
- and
- (b) detecting at least a portion of the maspin gene, wherein the portion of the maspin gene is differentially methylated from the portion of the maspin gene from the maternal DNA in the blood sample, thereby detecting the maspin gene from the fetus.
A method for detecting and monitoring a pregnancy-associated disorder, comprising the steps of:
- (a) obtaining DNA in a blood sample from the woman;
- (b) treating the DNA from step (a) with a reagent that differentially modifies methylated and non-methylated DNA;
- (c) determining the nucleotide sequence of at least a portion of the maspin gene from step (b);
- and
- (d) comparing the profile of the nucleotide sequences from step (c) with a standard control, wherein a change in the profile from the standard control indicates the presence or progression of a pregnancy-associated disorder.
-40. (canceled)
A method for detecting trisomy 18 in a fetus in a pregnant woman, comprising the steps of:
- (a) obtaining DNA in a blood sample from the woman;
- (b) treating the DNA from step (a) with a reagent that differentially modifies methylated and non-methylated DNA;
- and
- (c) determining the levels of different alleles of the maspin gene from the fetal DNA, thereby determining the ratio of the alleles, wherein the different alleles have different methylation profile in at least portion of the maspin gene, and wherein an increase or a decrease in the ratio from a standard control indicates the presence of trisomy 18 in the fetus.
-53. (canceled)
A method for detecting trisomy 18 in a fetus in a pregnant woman, comprising:
- (a) obtaining a blood sample from the woman;
- (b) determining the methylation status of at least a portion of the maspin gene in the blood sample, wherein the portion of the maspin gene from the fetus and the portion from the woman are differentially methylated, thereby distinguishing the maspin gene from the woman and the maspin gene from the fetus in the blood sample;
- and
- (c) determining the levels of two different alleles of the fetal maspin gene, wherein a deviation of the ratio of the levels of the two alleles from 1:1 indicates trisomy 18 in the fetus.
-56. (canceled)
Dependencies are inferred from the claim text.