Fetal cardiac anomalies and genetic syndromes

Cardiac anomalies may occur in isolation or can be part of a genetic syndrome. In this article, we describe some of the genetic syndromes commonly associated with cardiac anomalies where there are other sonographic features that may aid accurate prenatal diagnosis. Copyright © 2004 John Wiley & Sons, Ltd.     

Non-invasive fetal genotyping for maternal alleles with droplet digital PCR: A comparative study of analytical approaches

Objectives

To develop a flexible droplet digital PCR (ddPCR) workflow to perform non-invasive prenatal diagnosis via relative mutation dosage (RMD) for maternal pathogenic variants with a range of inheritance patterns, and to compare the accuracy of multiple analytical approaches.

Methods

Cell free DNA (cfDNA) was tested from 124 archived maternal plasma samples: 88 cases for sickle cell disease and 36 for rare Mendelian conditions. Three analytical methods were compared: sequential probability ratio testing (SPRT), Bayesian and z-score analyses.

Results

The SPRT, Bayesian and z-score analyses performed similarly well with correct prediction rates of 96%, 97% and 98%, respectively. However, there were high rates of inconclusive results for each cohort, particularly for z-score analysis which was 31% overall. Two samples were incorrectly classified by all three analytical methods; a false negative result predicted for a fetus affected with sickle cell disease and a false positive result predicting the presence of an X-linked IDS variant in an unaffected fetus.

Conclusions

ddPCR can be applied to RMD for diverse conditions and inheritance patterns, but all methods carry a small risk of erroneous results. Further evaluation is required both to reduce the rate of inconclusive results and explore discordant results in more detail.     

Comparison of Two Types of Metapopulation Models in Real and Artificial Landscapes

Abstract: Application of metapopulation models is becoming increasingly widespread in the conservation of species in fragmented landscapes. We provide one of the first detailed comparisons of two of the most common modeling techniques, incidence function models and stage-based matrix models, and test their accuracy in predicting patch occupancy for a real metapopulation. We measured patch occupancies and demographic rates for regional populations of the Florida scrub lizard (   Sceloporus woodi ) and compared the observed occupancies with those predicted by each model. Both modeling strategies predicted patch occupancies with good accuracy ( 77–80%) and gave similar results when we compared hypothetical management scenarios involving removal of key habitat patches and degradation of habitat quality. To compare the two modeling approaches over a broader set of conditions, we simulated metapopulation dynamics for 150 artificial landscapes composed of equal-sized patches (2–1024 ha) spaced at equal distances (50–750 m). Differences in predicted patch occupancy were small to moderate (<20%) for about 74% of all simulations, but 22% of the landscapes had differences openface> 50%. Incidence function models and stage-based matrix models differ in their approaches, assumptions, and requirements for empirical data, and our findings provide evidence that the two models can produce different results. We encourage researchers to use both techniques and further examine potential differences in model output. The feasibility of obtaining data for population modeling varies widely among species and limits the modeling approaches appropriate for each species. Understanding different modeling approaches will become increasingly important as conservation programs undertake the challenge of managing for multiple species in a landscape context.     

Molecular prenatal diagnosis: the impact of modern technologies

Originally prenatal diagnosis was confined to the diagnosis of metabolic disorders and depended on assaying enzyme levels in amniotic fluid. With the development of recombinant DNA technology, molecular diagnosis became possible for some genetic conditions late in the 1970s. Here we briefly review the history of molecular prenatal diagnostic testing, using Duchenne muscular dystrophy as an example, and describe how over the last 30 years we have moved from offering testing to a few affected individuals using techniques, such as Southern blotting to identify deletions, to more rapid and accurate PCR-based testing which identifies the precise change in dystrophin for a greater number of families. We discuss the potential for safer, earlier prenatal genetic diagnosis using cell free fetal DNA in maternal blood before concluding by speculating on how more recent techniques, such as next generation sequencing, might further impact on the potential for molecular prenatal testing. Progress is not without its challenges, and as cytogenetics and molecular genetics begin to unite into one, we foresee the main challenge will not be in identifying the genetic change, but rather in interpreting its significance, particularly in the prenatal setting where we frequently have no phenotype on which to base interpretation. Copyright © 2010 John Wiley & Sons, Ltd.