Marker for prenatal diagnosis and monitoring
AssigneeThe Chinese University of Hong Kong
InventorsYuk Ming Dennis Lo, Rossa Wai Kwun 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.
Claims30
A method for detecting preeclampsia in a woman pregnant with a fetus, comprising the steps of:
- (a) obtaining a blood sample from the woman after the 10th week of gestation;
- (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 from the standard control indicates the presence of preeclampsia.
A method for detecting preeclampsia in a woman pregnant with a fetus, comprising the steps of:
- (a) obtaining DNA in a blood sample from the woman after the 10th week of gestation;
- (b) treating the DNA from step (a) with bisulfite;
- 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 to the portion of the maspin gene from the fetus but not to the portion of the maspin gene from the maternal DNA;
- and
- (d) comparing the level of the amplified portion of the maspin gene from step (c) with a standard control, wherein an increase from the standard control indicates the presence of preeclampsia.
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 preeclampsia in a woman pregnant with a fetus, comprising the steps of:
- (a) obtaining DNA in a blood sample from the woman after the 10th week of gestation;
- (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 of preeclampsia.
Dependencies are inferred from the claim text.