Disease associated gene deficient embryonic stem cells can serve as valuable in vitro models to study disease mechanisms and screen drugs. Smad3 mediated TGF-β/Activin/Nodal signaling plays important roles in many biological processes. Despite numerous studies regarding Smad3 function, the role of Smad3 in mouse ES cells is not well studied. To understand the function of Smad3 in mouse ES cells, we derived Smad3-/- ES cells and wild type ES cells. Smad3-/- ES cells display no defect on self-renewal. They express similar level of pluripotent genes and lineage genes compared to wild type ES cells. However, Smad3 ablation results in transient difference in germ layer marker expression during embryoid body formation. Mesoderm lineage marker expression is significantly reduced in the embryoid body formed by Smad3-/- ES cells compared to wild type ES cells. Intriguingly, subcutaneous injection of Smad3-/- ES cells into nude mice leads to formation of malignant immature teratomas, whilst wild type ES cells tend to form mature teratomas. Smad3-/- ES cell formed teratomas can therefore provide a new model for the study of the mechanism of malignant teratomas.

60% of pregnant Chinese women prefer NIPT over CMA when screened as high risk for Down syndrome.

Chromosome copy number variants (CNVs; gains and losses of DNA sequences >1 kb) are wide-spread throughout the genome of healthy individuals. Laboratory studies show that a subset of CNVs are pathogenic, and not only can be responsible for the pathogenesis of major birth defects and cancer, but are also associated with neurodevelopmental disorders at birth. The characteristics of the pathogenic microdeletions and microduplications are important for both clinical implications and genetic counselling regarding test selection for prenatal screening and diagnosis. Unfortunately, our knowledge of the phenotypic effects of most CNV is still minimal, leading to the classification of many CNVs as "genomic imbalances of unknown clinical significance". Microdeletions and microduplications can occur in all pregnancies and the spectrum of pathogenic CNVs in fetuses with syndromic malformations is not well studied. This review summarizes our current understanding of CNVs, the common detection methods, and the characteristics of pathogenic CNVs identified in fetuses with syndromic malformations. Birth Defects Research 109:725-733, 2017. © 2017 Wiley Periodicals, Inc.

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