SAN DIEGO–Sequenom, Inc. (NASDAQ:SQNM – News), announced that breakthrough data from a collaborative project with The Chinese University of Hong Kong, supporting the noninvasive prenatal diagnosis of monogenic diseases, were published online today in the Early Edition of the Proceedings of the National Academy of Sciences. Monogenic diseases, which include cystic fibrosis, â-thalassemia and sickle cell anemia, could only be definitively diagnosed prenatally through invasive procedures following extensive carrier screening testing on both parents. In the United States, cystic fibrosis screening is recommended for all women of child bearing age (over 10 million individuals in the U.S. are carriers of the CF mutated gene, including one in every 29 Caucasian Americans) and in certain regions of the world, â-thalassemia affects anywhere from three to 16 percent of the population. Sequenom holds exclusive rights to this breakthrough technology representing a new approach that could potentially eliminate the need for paternal testing and significantly reduce the use of invasive tests.

“This new study addresses a problem that has been puzzling investigators in the field of noninvasive prenatal diagnosis over the last ten years,” stated Dennis Lo, M.D. Ph.D., study co-author and Li Ka Shing Professor of Medicine at The Chinese University of Hong Kong. “Digital PCR technologies have enabled us to measure the minute imbalance of mutant and normal DNA sequences in maternal plasma. This has freed us from the past restriction for monogenic disease analysis where we could only look at the paternally-inherited mutations noninvasively. This research represents a significant paradigm shift in the way we approach plasma DNA-based diagnostics, and offers substantial promise for bringing noninvasive prenatal diagnosis of monogenic diseases closer to reality.”

Data from the collaborative project show for the first time that when individual mutant or normal DNA sequences are counted in maternal plasma using digital PCR technology, the number of mutant genes inherited by an unborn fetus, and hence its disease status, can be determined. The authors further demonstrated that a ‘molecular counting’ strategy can be made more efficient by taking into account the length of the DNA molecules in maternal plasma, as fetal DNA molecules are known to typically be shorter than the maternally derived molecules in maternal plasma. Through the use of this digital counting approach, the authors were able to noninvasively diagnose â-thalassemia and hemoglobin E disease from maternal plasma – forms of inherited anemia that affect millions of people worldwide. This molecular counting strategy can in principle be applicable to all forms of monogenic diseases, namely paternally or maternally inherited autosomal dominant diseases and autosomal recessive diseases with any combination of parental mutations. Thus, the complete diagnosis of monogenic diseases can be achieved noninvasively.

“Sequenom is committed to developing the next-generation of prenatal diagnostic tools that will provide physicians with the capabilities they need to noninvasively diagnose genetic disorders early in a woman’s pregnancy,” said Harry Stylli, Ph.D., President and Chief Executive Officer of Sequenom. “Dr. Lo and his team have made another important breakthrough in prenatal diagnostics with these findings. These unique, noninvasive digital technologies have the potential to dramatically impact the prenatal diagnostic market and we look forward to continuing to work with Dr. Lo and his team to advance these innovative approaches as part of our long-term strategy to expand our prenatal diagnostics franchise.”

The study, entitled “Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma” by Lun et. al., is available online in this week’s Early Edition of PNAS at www.PNAS.org.

Monogenic Recessive Diseases

According to the World Health Organization, monogenic diseases result from modifications in a single gene occurring in all cells of the body. Though relatively rare for each disease, together they affect millions of people worldwide. Monogenic diseases are responsible for a heavy loss of lives. The global prevalence of all single gene diseases at birth is approximately 10/1,000. Scientists currently estimate that over 10,000 of human diseases are known to be monogenic. Pure genetic diseases are caused by a single error in a single gene in the human DNA. The nature of disease depends on the functions performed by the modified gene. The single-gene or monogenic diseases can be classified into three main categories: dominant, recessive, and X-linked.

All human beings have two sets or copies of each gene called alleles; one copy on each chromosome pair. Recessive diseases are monogenic disorders that occur from an individual having inherited two defective copies or alleles. Dominant diseases are monogenic disorders that involve defects to only one gene copy.

Prenatal diagnosis of monogenic diseases is currently performed by invasive procedures such as amniocentesis and chorionic villus sampling (CVS) which carry a risk of fetal miscarriage. The discovery of cell-free fetal DNA in maternal plasma offers noninvasive prenatal diagnostics which eliminate the risk to the fetus. For many monogenic diseases of medical interest, a different quantitative approach is needed. For example, for monogenic recessive diseases like cystic fibrosis and â-thalassemia, the fetus would need to have inherited two copies of the mutant gene to suffer from the disease. The inheritance of only one mutant gene signifies a disease carrier while inheritance of no mutant gene (or in other words, having inherited two normal genes) indicates a healthy fetus. However, such a precise degree of mutation quantification for noninvasive prenatal diagnosis has not previously been possible due to the presence of a high background of maternal DNA interfering with the analysis of the small amount of circulating fetal DNA in maternal plasma.

Sequenom’s Proprietary Noninvasive Prenatal Diagnostics

Sequenom’s commercial opportunities in prenatal diagnostics are built upon its SEQureDx™ technologies and are enabled by the pioneering inventions and associated intellectual property rights that it has exclusively licensed from Isis Innovation Ltd., the technology transfer company of the University of Oxford, as well as The Chinese University of Hong Kong. Sequenom’s portfolio of noninvasive prenatal diagnostic patent rights and patent applications is platform-independent, includes genetic-analysis methods using circulating cell-free fetal nucleic acids from maternal serum, plasma or whole blood, and also includes a portfolio of methylation and nucleic-acid markers. Sequenom holds exclusive rights in territories including the United States, Europe, Australia, Canada, Japan and Hong Kong. Sequenom is actively expanding its intellectual property position with new technology and new territories. Because Sequenom’s license rights are platform-independent, the rights provide exclusivity (with the narrow exception in Europe for RT-PCR-based Rhesus D tests) for development and commercialization of noninvasive prenatal screens and tests on any platform and are not limited to the Company’s MassARRAY® platform.