文献_2012-Noninvasive Prenatal Diagnosis of Monogenic Diseases by Targeted Massively ParallelSequencing of Maternal Plasma Application to β Thalassemia.pdfVIP

Papers in Press. Published August 15, 2012 as doi:10.1373/clinchem.2012.189589 The latest version is at /cgi/doi/10.1373/clinchem.2012.189589 Clinical Chemistry 58:10 Molecular Diagnostics and Genetics 000–000 (2012) Noninvasive Prenatal Diagnosis of Monogenic Diseases by Targeted Massively Parallel Sequencing of Maternal Plasma: Application to Thalassemia Kwan-Wood G. Lam,1,2 Peiyong Jiang,1,2 Gary J.W. Liao,1,2 K.C. Allen Chan,1,2 Tak Y. Leung,3 Rossa W.K. Chiu,1,2 and Y.M. Dennis Lo1,2* BACKGROUND: A genomewide genetic and mutational The discovery of cell-free fetal nucleic acids in maternal profile of a fetus was recently determined via deep se- plasma during pregnancy has opened up new possibil- quencing of maternal plasma DNA. This technology ities for noninvasive prenatal diagnosis (NIPD)4 (1). couldhaveimportantapplicationsfornoninvasiveprena- Maternal plasma consists of a mixture of DNA from tal diagnosis (NIPD) of many monogenic diseases. Rela- the fetus and the mother and thus represents consider- tive haplotype dosage (RHDO) analysis, a core step of this able challenges for many of its applications. The recent procedure, would allow one to elucidate the maternally advent of massively parallel sequencing has catalyzed inherited half of the fetal genome. For clinical applica- the development of clinical applications of circulating tions, the cost and complexity of data analysis might be fetal DNA for NIPD (2). Thus, use of this approach reduced via targeted application of this approach to se- with maternal plasma has allowed the robust detection lected genomic regions contain