The Chinese University of Hong Kong

Boston University

The Third People's Hospital of Shenzhen

Chunming Ding

Yuk Ming Dennis Lo

Charles Cantor

Rossa Wai Kwun Chiu

Stephen Siu Chung Chim

Wai Kwun Rossa Chiu

Kwan Chee Chan

Yu-Kwan Tong

Hing Nam Ivy Wong

Ka Chun Ryan Yuen

Yuk-Ming Dennis Lo

Kwan Chee Allen Chan

Yu Kwan Tong

Yu-kwan Tong

Bo Yin Tsui

Stephen Siu-Chung Chim

Shengnan Jin

Xinchun Chen

Hongmei Zhang

Ju Luan

Boping Zhou

Jing Yuan

Tracy Yuen Han Lee

Fiona Miu Fun Lun

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.

Marker for prenatal diagnosis and monitoring

The present invention concerns a method for the detection or monitoring of cancer using a biological sample selected from blood, plasma, serum, saliva, urine from an individual, said method comprising:

Diagnostic method

Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment.

Methods and kits for selectively amplifying, detecting or quantifying target DNA with specific end sequences

The present invention is directed to a method for detecting and quantifying rare mutations in a nucleic acid sample. The nucleic acid molecules under investigation can be either DNA or RNA. The rare mutation can be any type of functional or non-functional nucleic acid change or mutation, such as deletion, insertion, translocation, inversion, one or more base substitution or polymorphism. Therefore, the methods of the present invention are useful in detection of rare mutations in, for example, diagnostic, prognostic and follow-up applications, when the targets are rare known nucleic acid variants mixed in with the wildtype or the more common nucleic acid variant(s).

Method for detecting and quantifying rare mutations/polymorphisms

This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

Fetal methylation markers

The present invention provides an efficient way for high throughput haplotype analysis. Several polymorphic nucleic acid markers, such as SNPs, can be simultaneously and reliably determined through multiplex PCR of single nucleic acid molecules in several parallel single molecule dilutions and the consequent statistical analysis of the results from these parallel single molecule multiplex PCR reactions results in reliable determination of haplotypes present in the subject. The nucleic acid markers can be of any distance to each other on the chromosome. In addition, an approach wherein overlapping DNA markers are analyzed can be used to link smaller haplotypes into larger haplotypes. Consequently, the invention provides a powerful new tool for diagnostic haplotyping and identifying novel haplotypes.

Haplotype analysis

Disclosed is a method for the detection of virus variations. Disclosed also is a method for the treatment of virus infection in a subject based on the detection of virus variations. Additionally, a kit is provided for the detection of virus variations.

Multiplex detection of hepatitis virus variations

The present invention relates to a method for measuring the amount of a target nucleic acid in a sample using a standard which is designed to have one base difference compared with the gene of interest or a 'target nucleic acid sequence.' Use of such standard in combination with a method of 'enhancing' the difference in the standard and the test nucleic acid sample using, for example, a base extension reaction carried right at the mutation site allowing amplification of the standard and target nucleic acids with the same efficiency and facilitating quantification of the target nucleic acid. Thereafter a means of quantifying the &#x201c;enhanced&#x201d; standard and target nucleic acid samples is used to determine the amount of the target nucleic acid. In the preferred embodiment, the quantification means is Mass Spectrometry.

Quantification of gene expression

Methods for detecting fetal DNA in a plasma or serum sample from a pregnant woman

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Singapore, Singapore

Chunming Ding